scholarly journals Bone Status in a Mouse Model of Experimental Autoimmune-Orchitis

2021 ◽  
Vol 22 (15) ◽  
pp. 7858
Author(s):  
Fabian Hemm ◽  
Monika Fijak ◽  
Jan Belikan ◽  
Marian Kampschulte ◽  
Thaqif El Khassawna ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Metabolism ◽  
Connexin 43 ◽  
Bending Test ◽  
Micro Computed Tomography ◽  
Laboratory Findings ◽  
Bone Status ◽  
Autoimmune Orchitis ◽  
The Impact ◽  
Experimental Autoimmune

Investigations in male patients with fertility disorders revealed a greater risk of osteoporosis. The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration. Hence, we investigated the impact of testicular dysfunction in EAO on bone status. Male mice were immunized with testicular homogenate in adjuvant to induce EAO (n = 5). Age-matched mice were treated with adjuvant alone (adjuvant, n = 6) or remained untreated (control, n = 7). Fifty days after the first immunization specimens were harvested. Real-time reverse transcription-PCR indicated decreased bone metabolism by alkaline phosphatase and Cathepsin K as well as remodeling of cell-contacts by Connexin-43. Micro computed tomography demonstrated a loss of bone mass and mineralization. These findings were supported by histomorphometric results. Additionally, biomechanical properties of femora in a three-point bending test were significantly altered. In summary, the present study illustrates the induction of osteoporosis in the investigated mouse model. However, results suggest that the major effects on bone status were mainly caused by the complete Freund’s adjuvant rather than the autoimmune-orchitis itself. Therefore, the benefit of the EAO model to transfer laboratory findings regarding bone metabolism in context with orchitis into a clinical application is limited.

scholarly journals Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Louisane Desbiens ◽  
Catherine Lapointe ◽  
Marjan Gharagozloo ◽  
Shaimaa Mahmoud ◽  
Gunnar Pejler ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Score ◽  
Autoimmune Encephalomyelitis ◽  
Mast Cell Protease ◽  
Mouse Mast Cell ◽  
The Impact ◽  
Early Phases ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized withMOG35–55plus complete Freund’s adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.

1509: Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 409-409
Author(s):  
Masami Watanabe ◽  
Atsushi Nagai ◽  
Norihiro Kusumi ◽  
Yasutomo Nasu ◽  
Hiromi Kumon ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adeno Associated Virus ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

1875-P: The Impact of Carbohydrate/Fat Intake Balance on Beta-Cell Dedifferentiation and Fatty Liver in Obese Mouse Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1875-P ◽  
Author(s):  
EMI ISHIDA ◽  
XIAO LEI ◽  
EIJIRO YAMADA ◽  
SHUICHI OKADA ◽  
MASANOBU YAMADA
Keyword(s):  
Mouse Model ◽  
Beta Cell ◽  
Fatty Liver ◽  
Obese Mouse ◽  
Fat Intake ◽  
Cell Dedifferentiation ◽  
The Impact

scholarly journals Evaluation of the Impact of Different Pain Medication and Proton Pump Inhibitors on the Osteogenic Differentiation Potential of hMSCs Using 99mTc-HDP Labelling

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 339
Author(s):  
Tobias Grossner ◽  
Uwe Haberkorn ◽  
Tobias Gotterbarm
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Metabolism ◽  
Negative Impact ◽  
Pain Medication ◽  
Group 3 ◽  
Group 5 ◽  
The Impact

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive 99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.

scholarly journals Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Lichtman ◽  
Eyal Bergmann ◽  
Alexandra Kavushansky ◽  
Nadav Cohen ◽  
Nina S. Levy ◽  
...  
Keyword(s):  
Social Behavior ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Ampa Receptor ◽  
Social Preference ◽  
Autism Spectrum ◽  
Receptor Trafficking ◽  
Anterior Cingulate ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

scholarly journals Relative Frequency and Risk Factors of COVID-19 Related Headache in a Sample of Egyptian Population: A Hospital-Based Study

Pain Medicine ◽  
2021 ◽  
Author(s):  
Mona Hussein ◽  
Wael Fathy ◽  
Ragaey A Eid ◽  
Hoda M Abdel-Hamid ◽  
Ahmed Yehia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Platelet Count ◽  
Relative Frequency ◽  
Clinical Laboratory ◽  
Primary Headache ◽  
Female Gender ◽  
Imaging Data ◽  
Laboratory Findings ◽  
Neutrophil Lymphocyte Ratio ◽  
The Impact

Abstract Objectives Headache is considered one of the most frequent neurological manifestations of coronavirus disease 2019 (COVID-19). This work aimed to identify the relative frequency of COVID-19-related headache and to clarify the impact of clinical, laboratory findings of COVID-19 infection on headache occurrence and its response to analgesics. Design Cross-sectional study. Setting Recovered COVID-19 patients. Subjects In total, 782 patients with a confirmed diagnosis of COVID-19 infection. Methods Clinical, laboratory, and imaging data were obtained from the hospital medical records. Regarding patients who developed COVID-19 related headache, a trained neurologist performed an analysis of headache and its response to analgesics. Results The relative frequency of COVID-19 related headache among our sample was 55.1% with 95% confidence interval (CI) (.516–.586) for the estimated population prevalence. Female gender, malignancy, primary headache, fever, dehydration, lower levels of hemoglobin and platelets and higher levels of neutrophil/lymphocyte ratio (NLR) and CRP were significantly associated with COVID-19 related headache. Multivariate analysis revealed that female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count were independent predictors of headache occurrence. By evaluating headache response to analgesics, old age, diabetes, hypertension, primary headache, severe COVID-19, steroid intake, higher CRP and ferritin and lower hemoglobin levels were associated with poor response to analgesics. Multivariate analysis revealed that primary headache, steroids intake, moderate and severe COVID-19 were independent predictors of non-response to analgesics. Discussion Headache occurs in 55.1% of patients with COVID-19. Female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count are considered independent predictors of COVID-19 related headache.

scholarly journals SARS-CoV-2/DENV co-infection: a series of cases from the Federal District, Midwestern Brazil

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Heidi Luise Schulte ◽  
José Diego Brito-Sousa ◽  
Marcus Vinicius Guimarães Lacerda ◽  
Luciana Ansaneli Naves ◽  
Eliana Teles de Gois ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Federal District ◽  
Therapeutic Interventions ◽  
Diagnostic Process ◽  
The Novel ◽  
Prevention Measures ◽  
Laboratory Findings ◽  
Novel Coronavirus ◽  
The Impact

Abstract Background Since the novel coronavirus disease outbreak, over 179.7 million people have been infected by SARS-CoV-2 worldwide, including the population living in dengue-endemic regions, particularly Latin America and Southeast Asia, raising concern about the impact of possible co-infections. Methods Thirteen SARS-CoV-2/DENV co-infection cases reported in Midwestern Brazil between April and September of 2020 are described. Information was gathered from hospital medical records regarding the most relevant clinical and laboratory findings, diagnostic process, therapeutic interventions, together with clinician-assessed outcomes and follow-up. Results Of the 13 cases, seven patients presented Acute Undifferentiated Febrile Syndrome and six had pre-existing co-morbidities, such as diabetes, hypertension and hypopituitarism. Two patients were pregnant. The most common symptoms and clinical signs reported at first evaluation were myalgia, fever and dyspnea. In six cases, the initial diagnosis was dengue fever, which delayed the diagnosis of concomitant infections. The most frequently applied therapeutic interventions were antibiotics and analgesics. In total, four patients were hospitalized. None of them were transferred to the intensive care unit or died. Clinical improvement was verified in all patients after a maximum of 21 days. Conclusions The cases reported here highlight the challenges in differential diagnosis and the importance of considering concomitant infections, especially to improve clinical management and possible prevention measures. Failure to consider a SARS-CoV-2/DENV co-infection may impact both individual and community levels, especially in endemic areas.

scholarly journals Male Fetal Sex Affects Uteroplacental Angiogenesis in Growth Restriction Mouse Model†

2021 ◽  
Author(s):  
Jessica F Hebert ◽  
Jess A Millar ◽  
Rahul Raghavan ◽  
Amie Romney ◽  
Jason E Podrabsky ◽  
...  
Keyword(s):  
Mouse Model ◽  
Killer Cell ◽  
Receptor Activation ◽  
Growth Restriction ◽  
Late Gestation ◽  
Spiral Artery ◽  
Micro Computed Tomography ◽  
Fetal Sex ◽  
Maternal Genotype ◽  
Agt Gene

Abstract Abnormally increased angiotensin II activity related to maternal angiotensinogen (AGT) genetic variants, or aberrant receptor activation, is associated with small-for-gestational-age (SGA) babies and abnormal uterine spiral artery remodeling in humans. Our group studies a murine AGT gene titration transgenic (TG; 3-copies of the AGT gene) model, which has a 20% increase in AGT expression mimicking a common human AGT genetic variant (A[−6]G) associated with intrauterine growth restriction (IUGR) and spiral artery pathology. We hypothesized that aberrant maternal AGT expression impacts pregnancy-induced uterine spiral artery angiogenesis in this mouse model leading to IUGR. We controlled for fetal sex and fetal genotype (e.g., only 2-copy wild-type [WT] progeny from WT and TG dams were included). Uteroplacental samples from WT and TG dams from early (days 6.5 and 8.5), mid (d12.5), and late (d16.5) gestation were studied to assess uterine natural killer cell (uNK) phenotypes, decidual metrial triangle angiogenic factors, placental growth and capillary density, placental transcriptomics, and placental nutrient transport. Spiral artery architecture was evaluated at day 16.5 by contrast-perfused three-dimensional micro-computed tomography (3D microCT). Our results suggest that uteroplacental angiogenesis is significantly reduced in TG dams at day 16.5. Males from TG dams are associated with significantly reduced uteroplacental angiogenesis from early to late gestation compared with their female littermates and WT controls. Angiogenesis was not different between fetal sexes from WT dams. We conclude that male fetal sex compounds the pathologic impact of maternal genotype in this mouse model of growth restriction.

scholarly journals Mechanical Properties of Spruce Wood Extracted from GLT Beams Loaded by Fire

2021 ◽  
Vol 13 (10) ◽  
pp. 5494
Author(s):  
Lucie Kucíková ◽  
Michal Šejnoha ◽  
Tomáš Janda ◽  
Jan Sýkora ◽  
Pavel Padevět ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
High Temperature ◽  
Cross Section ◽  
Negative Impact ◽  
Tensile Tests ◽  
Thermal Recovery ◽  
Bending Test ◽  
Small Scale ◽  
Spruce Wood ◽  
The Impact

Heating wood to high temperature changes either temporarily or permanently its physical properties. This issue is addressed in the present contribution by examining the effect of high temperature on residual mechanical properties of spruce wood, grounding on the results of full-scale fire tests performed on GLT beams. Given these tests, a computational model was developed to provide through-thickness temperature profiles allowing for the estimation of a charring depth on the one hand and on the other hand assigning a particular temperature to each specimen used subsequently in small-scale tensile tests. The measured Young’s moduli and tensile strengths were accompanied by the results from three-point bending test carried out on two groups of beams exposed to fire of a variable duration and differing in the width of the cross-section, b=100 mm (Group 1) and b=160 mm (Group 2). As expected, increasing the fire duration and reducing the initial beam cross-section reduces the residual bending strength. A negative impact of high temperature on residual strength has also been observed from simple tensile tests, although limited to a very narrow layer adjacent to the charring front not even exceeding a typically adopted value of the zero-strength layer d0=7 mm. On the contrary, the impact on stiffness is relatively mild supporting the thermal recovery property of wood.

scholarly journals Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity

2021 ◽  
Vol 22 (2) ◽  
pp. 596
Author(s):  
Agnes Schröder ◽  
Joshua Gubernator ◽  
Alexandra Leikam ◽  
Ute Nazet ◽  
Fabian Cieplik ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Dietary Salt ◽  
Osteoclast Activity ◽  
Salt Uptake ◽  
Periodontal Bone Loss ◽  
The Impact

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

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