scholarly journals Morphological and ultrastructural analysis of normal, injured and osteoarthritic human knee menisci

2019 ◽  
Vol 63 (1) ◽  
Author(s):  
Michela Battistelli ◽  
Marta Favero ◽  
Debora Burini ◽  
Giovanni Trisolino ◽  
Dante Dallari ◽  
...  
Keyword(s):  
Structural Changes ◽  
Complex Geometry ◽  
Chromatin Condensation ◽  
Meniscal Tear ◽  
Joint Stability ◽  
Future Design ◽  
Meniscal Tissue ◽  
Treatment Indications ◽  
Healthy Control ◽  
End Stage

The human meniscus plays a crucial role for transmission and distribution of load across the knee, as well as shock absorption, joint stability, lubrication, and congruity. The aim of this study was to compare the complex geometry, and unique ultrastructure and tissue composition of the meniscus in healthy (control) and pathological conditions to provide understanding of structural changes that could be helpful in the future design of targetted therapies and improvement of treatment indications. We analyzed meniscus samples collected from 3 healthy multi-organ donors (median age, 66 years), 5 patients with traumatic meniscal tear (median age, 41 years) and 3 patients undergoing total knee replacement (TKR) for end-stage osteoarthritis (OA) (median age, 72 years). We evaluated the extracellular matrix (ECM) organization, the appearance and distribution of areas of calcification, and modifications of cellular organization and structure by electron microscopy and histology. The ECM structure was similar in specimens from traumatic meniscus tears compared to those from patients with late-stage OA, showing disorganization of collagen fibers and increased proteoglycan content. Cells of healthy menisci showed mainly diffuse chromatin and well preserved organelles. Both in traumatic and in OA menisci, we observed increased chromatin condensation, organelle degeneration, and cytoplasmic vacuolization, a portion of which contained markers of autophagic vacuoles. Areas of calcification were also observed in both traumatic and OA menisci, as well as apoptotic-like features that were particularly prominent in traumatic meniscal tear samples. We conclude that meniscal tissue from patients with traumatic meniscal injury demonstrate pathological alterations characteristic of tissue from older patients undergoing TKR, suggesting that they have high susceptibility to develop OA.

Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Adam S. Bernstein ◽  
Steven Z. Rapcsak ◽  
Michael Hornberger ◽  
Manojkumar Saranathan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Structural Changes ◽  
Thalamic Nuclei ◽  
Medial Temporal Lobes ◽  
Cognitive Changes ◽  
Temporal Lobes ◽  
Medial Geniculate ◽  
Healthy Control

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

Ultrastructural changes of Basolateral Amygdaloid nuclei in the Sprague Dawley rats brain following exposure to naphthalene balls

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K
Keyword(s):  
Structural Changes ◽  
Corn Oil ◽  
Chromatin Condensation ◽  
Ultrastructural Changes ◽  
High Dose ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Amygdaloid Nuclei

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.

scholarly journals Viral hepatitis and liver cancer

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160274 ◽  
Author(s):  
Marc Ringehan ◽  
Jane A. McKeating ◽  
Ulrike Protzer
Keyword(s):  
Liver Cirrhosis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Viral Infections ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Oncogenic Viruses ◽  
Chronic Infections ◽  
Future Design ◽  
End Stage

Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors. This article is part of the themed issue ‘Human oncogenic viruses’.

Erythrocyte Adhesion in Hemodialysis Patients – A Novel Potential Contributor to Inflammation in End-Stage Renal Disease.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2092-2092
Author(s):  
Vimal K. Derebail ◽  
Adam McDonald ◽  
Julia Brittain
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Renal Disease ◽  
Sickle Cell ◽  
End Stage Renal Disease ◽  
Sickle Cell Trait ◽  
Hemodialysis Patients ◽  
Healthy Control ◽  
Stage Renal Disease ◽  
End Stage

Abstract Abstract 2092 Background: Widespread adhesion of erythrocytes in the vasculature would be incompatible with life. However, in illnesses such as sickle cell disease, malaria and diabetes, adhesive RBCs have been documented and are likely contributors to disease severity, inflammation and coagulation activation. End-stage renal disease is characterized by profound, global inflammation and relative thrombophilia. While we, and others, have reported the extensive exposure of RBC phosphatidylserine in patients on hemodialysis, the role of RBC adhesion in inflammation has never been examined in this condition. We performed an analysis of RBCs from hemodialysis patients to characterize their ability to adhere to other cells, elucidate the potential mechanisms of adhesion, and to relate RBC adhesion to the inflammatory state of hemodialysis. Methods: This study was conducted in a cohort of 20 African American patients receiving in-center hemodialysis at 2 separate dialysis clinics as part of a study of sickle cell trait in hemodialysis. There were 9 of 20 patients with documented sickle cell trait. Blood samples were drawn immediately pre-dialysis and prior to administration of heparin. Plasma samples were processed to minimize platelet activation, aliquoted, and frozen for batch analysis. Plasma factors (RANTES, CRP & CD40L) were analyzed via ELISA. Adhesion events in whole blood were detected via two color flow cytometry. Cause of renal failure, mode of venous access and relevant clinical data were obtained from patient charts. All adhesion assays with washed blood cells were conducted under static conditions using microvascular endothelial cells. All studies were compared to those results of healthy control patients (n =11). Spearman's regression analysis was performed to analyze the correlation between continuous variables. Mann-Whitney U and Kruskal Wallis tests were used to compare continuous variables between groups. A p<0.05 was considered significant. Results: We found that RBCs from patients on hemodialysis were significantly more adhesive than those from healthy controls. In whole blood, we detected marked RBC adhesion to T-cells (median % of T-cells bound to RBCs: 67.9 [hemodialysis] vs. 10.55 [healthy control]) and platelets (median % of platelets bound to RBCs: 33.0 vs. 1.1%). We also noted significant RBC adhesion to neutrophils (median % of neutrophils bound to RBCs: 11.0% vs. 0.1%). Incubation of healthy RBCs with plasma from hemodialysis patients, but not healthy control plasma, was sufficient to induce RBC adhesion to cultured endothelial cells (median RBCs/mm2: 8.0 vs. 0.5) and to T-cells (median % T-cells bound to RBCs: 30.0 vs. 5.0). Plasma from hemodialysis patients also induced phosphatidylserine exposure on healthy RBCs. Phosphatidylserine exposure on the RBC appeared to mediate RBC adhesion to endothelial cells as annexin V significantly reduced RBC adherence (8.0 vs 3.8 RBC/mm2). The extent to which RBCs in hemodialysis patients adhered to T-cells directly correlated with both plasma RANTES (rspearman = 0.65, 95% CI: 0.247–0.864) and CD40L levels (rspearman= 0.60, 95% CI: 0.1645 – 0.847), but not plasma CRP levels. There was also no significant difference in adhesion of RBCs due to cause of renal failure (diabetes, hypertension, or glomerulonephritis) or presence of sickle cell trait. Conclusions: We describe for the first time a novel adhesion of RBCs in patients receiving hemodialysis and how this adhesion may relate to inflammation in these patients. Our findings also suggest that factors in uremic plasma are sufficient to induce phosphatidylserine exposure on RBCs. This exposure, in addition to providing a site for thrombin generation, also serves as an adhesive moiety on RBCs for endothelial cells. These data may describe an unrecognized etiology of inflammation in hemodialysis and end-stage renal disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cellular senescence impairs the reversibility of pulmonary arterial hypertension

2020 ◽  
Vol 12 (554) ◽  
pp. eaaw4974 ◽  
Author(s):  
Diederik E. van der Feen ◽  
Guido P. L. Bossers ◽  
Quint A. J. Hagdorn ◽  
Jan-Renier Moonen ◽  
Kondababu Kurakula ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Structural Changes ◽  
Human Situation ◽  
Vascular Phenotype ◽  
Pulmonary Arterial ◽  
End Stage ◽  
Irreversible Nature

Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a senescent vascular phenotype and confirmed markers of senescence in human PAH-CHD tissue. In vitro, we showed that human pulmonary endothelial cells of patients with PAH are more vulnerable to senescence than controls in response to shear stress and confirmed that the senolytic ABT263 induces apoptosis in senescent, but not in normal, endothelial cells. To support the concept that vascular cell senescence is causal to the irreversible nature of end-stage PAH, we targeted senescence using ABT263 and induced reversal of the hemodynamic and structural changes associated with severe PAH refractory to HU. The factors that drive the transition from a reversible to irreversible pulmonary vascular phenotype could also explain the irreversible nature of other PAH etiologies and provide new leads for pharmacological reversal of end-stage PAH.

Dorsolateral and ventrolateral prefrontal cortex structural changes relative to suicidal ideation in patients with depression

2020 ◽  
Vol 32 (2) ◽  
pp. 84-91
Author(s):  
Ran Zhang ◽  
Shengnan Wei ◽  
Miao Chang ◽  
Xiaowei Jiang ◽  
Yanqing Tang ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Suicidal Ideation ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Major Depressive ◽  
Left Dlpfc ◽  
Healthy Control ◽  
Left And Right ◽  
And Gender ◽  
The Right

AbstractThe prefrontal cortex (PFC) is enormously important in suicide and major depressive disorder (MDD). However, little is known about the structural alterations in the brains of people with MDD and suicidal ideation. We examined the gray matter volume (GMV) of the PFC of individuals with MDD and suicidal ideation to determine if PFC volumetric differences contribute to suicidal ideation in patients with MDD. Thirty-five subjects with MDD and suicidal ideation, 38 subjects with MDD but without suicidal ideation, and 43 age- and gender-matched healthy control (HC) subjects underwent T1-weighted imaging. A voxel-based morphometric analysis was conducted to compare the PFC GMVs of the three groups. Further GMV reductions in the left and right dorsolateral PFC (DLPFC) and right ventrolateral PFC (VLPFC) were detected in the MDD with suicidal ideation group compared with those in the HC group and the MDD without suicidal ideation group, whereas the MDD without suicidal ideation group only exhibited significant differences in the left DLPFC relative to the HC group. Our findings demonstrated that left DLPFC reductions were associated with MDD and suicidal ideation, and diminished GMV reductions in the right DLPFC and right VLPFC were only associated with suicidal ideation. These results help us better understand the neuropathological changes in MDD with suicidal ideation.

scholarly journals Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jakob Appel Østergaard ◽  
Marieta Milkova Ruseva ◽  
Talat Habib Malik ◽  
Ingeborg Torp Hoffmann-Petersen ◽  
Matthew Caleb Pickering ◽  
...  
Keyword(s):  
Complement System ◽  
Drug Targets ◽  
Lectin Pathway ◽  
Diabetes Model ◽  
Healthy Control ◽  
End Stage ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin ◽  
Immunofluorescence Intensity

Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL), is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus.Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice.Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5) immunofluorescence intensity from anti-MBL antibodies compared with controls (P<0.001). Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (P=0.04).Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes.

scholarly journals Subtype distribution and molecular characterization of Blastocystis from hemodialysis patients in Turkey

2020 ◽  
Vol 14 (12) ◽  
pp. 1448-1454
Author(s):  
Baris Gulhan ◽  
Merve Aydin ◽  
Mehtap Demirkazik ◽  
Ismail Soner Koltas ◽  
Aytekin Cikman ◽  
...  
Keyword(s):  
Hemodialysis Patients ◽  
Sequencing Analysis ◽  
Two Samples ◽  
Blastocystis Subtype ◽  
Healthy Control ◽  
Stool Samples ◽  
Dna Sequencing Analysis ◽  
End Stage ◽  
Multiple Symptoms ◽  
Subtype Distribution

Introduction: The aim of this study was to determine the Blastocystis prevalence and subtypes in hemodialysis patients in Turkey. Methodology: Eighty-four patients diagnosed with end-stage renal failure who were undergoing hemodialysis and 20 healthy volunteers were enrolled. Blastocystis presence was investigated by native-Lugol, trichrome staining, PCR using STS primers, and DNA sequencing analysis. Results: Among the stool samples from the hemodialysis patients, 9.52% (8/84) were found to be Blastocystis-positive with the native-Lugol and trichrome staining. Seven of the eight Blastocystis isolates were subtyped using STS primers. Blastocystis subtype distribution was as follows: one had ST1, two had ST2, two had ST3, two had ST3+ST6, and one was not subtyped. Blastocystis positivity was detected in two healthy control (2/20, %10), one subject had ST1, and the other was not subtyped. All subtypes identified by PCR were confirmed by the sequencing analysis. In the two samples that had mixed subtypes (ST3+ST6) when using the STS primers, only ST3 was detected in the sequencing analysis. Although some patients have multiple symptoms, the most common symptoms in Blastocystis positive patients were bloating (5/8), diarrhea (4/8), nausea and vomiting (2/8), and gas and weight loss (1/8). Also, only one patient had Giardia intestinalis. Conclusions: This was the first study to determine the Blastocystis subtypes in hemodialysis patients. A rare subtype, ST6, was identified in two of the patients. Thus, the ST6 infections were attributable to transmission from poultry infections. The presence of this unusual subtype suggests the need for further extensive studies of hemodialysis patients.

Impairment of the antioxidant properties of serum albumin in patients with diabetes: protective effects of metformin

2008 ◽  
Vol 114 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Patrice Faure ◽  
Nicolas Wiernsperger ◽  
Camille Polge ◽  
Alain Favier ◽  
Serge Halimi
Keyword(s):  
Oxidative Stress ◽  
Fluorescence Quenching ◽  
Serum Albumin ◽  
Structural Changes ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
Control Subjects ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
Healthy Control

Free radical production is increased during diabetes. Serum albumin is a major antioxidant agent, and structural modification of albumin induced by glucose or free radicals impairs its antioxidant properties. Therefore the aim of the present study was to compare the antioxidant capacities and structural changes in albumin in patients with T2DM (Type 2 diabetes mellitus) treated with MET (metformin) or SU (sulfonylureas) and in healthy control subjects. Structural changes in albumin were studied by fluorescence quenching in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidized and glycation-induced changes in serum albumin respectively, were assessed. Structural changes in albumin were demonstrated by a significant decrease in fluorescence quenching in patients with T2DM, with patients treated with MET exhibiting a significant difference in the conformation of albumin compared with patients treated with SU. Oxidation, resulting in a significant decrease in thiol groups and plasma total antioxidant capacity, and glycation, associated with a significant increase in fructosamines, were both found when comparing healthy control subjects with patients with T2DM. When patients treated with MET were compared with those treated with SU, oxidative stress and glycation were found to be significantly lower in MET-treated patients. In conclusion, patients with T2DM have a decrease in the antioxidant properties of serum albumin which may aggravate oxidative stress and, thus, contribute to vascular and metabolic morbidities. Moreover, a significant protection of albumin was found in patients with T2DM treated with MET.

scholarly journals Molecular cloning and expression of a cDNA encoding an apoptotic endonuclease DNase γ

1998 ◽  
Vol 332 (3) ◽  
pp. 713-720 ◽  
Author(s):  
Daisuke SHIOKAWA ◽  
Sei-ichi TANUMA
Keyword(s):  
Lymph Nodes ◽  
Molecular Cloning ◽  
Dna Fragmentation ◽  
Structural Changes ◽  
Divalent Cations ◽  
Chromatin Condensation ◽  
Cloning And Expression ◽  
Dnase Γ ◽  
Hela S3 ◽  
Hela S3 Cells

An endonuclease named DNase γ has been purified from the nuclei of apoptotic rat thymocytes [Shiokawa, Ohyama, Yamada and Tanuma (1997) Biochem. J. 326, 675–681]. Here we report the molecular cloning of a cDNA encoding a 35 kDa precursor protein for rat DNase γ. A 1.6 kb mRNA coding for the DNase γ precursor is detected at high levels in spleen, lymph nodes, thymus and liver. By using reverse transcriptase-mediated PCR, expression of DNase γ mRNA is observed in kidney and testis but not in brain or heart. Analysis of recombinant DNase γ reveals that full-length DNase γ, including the N-terminal precursor, is an inactive proenzyme. The mature form of recombinant DNase γ, from which the N-terminal precursor has been removed, has the same properties as purified DNase γ: requirement for divalent cations, dependence on pH, sensitivity to Zn2+, and cleavage of chromosome DNA to nucleosomal units. In HeLa S3 cells stably transfected with the DNase γ cDNA, exogenously introduced DNase γ is activated by apoptotic stimuli; enhancement of DNA fragmentation, chromatin condensation and nuclear collapse are observed. These findings provide evidence for the involvement of DNase γ in DNA fragmentation and nuclear structural changes during apoptosis.

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