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Journal of Neuropathology and... Nov 2014The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the...
The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.
Topics: Aged; Aged, 80 and over; Arteriolosclerosis; Blood-Brain Barrier; Brain; Cerebral Small Vessel Diseases; Cohort Studies; Female; Humans; Male; Single-Blind Method
PubMed: 25289893
DOI: 10.1097/NEN.0000000000000124 -
Nephrology, Dialysis, Transplantation :... Nov 2015Nephrosclerosis is an umbrella term defining changes in all compartments of the kidney, changes caused by hypertension and by ageing. Among other lesions,... (Review)
Review
Nephrosclerosis is an umbrella term defining changes in all compartments of the kidney, changes caused by hypertension and by ageing. Among other lesions, arteriolosclerosis and arteriolohyalinosis play a major role in inducing glomerular ischaemic shrinking and sclerosis along with glomerulomegaly and focal-segmental glomerulosclerosis (FSGS). These lesions are accompanied by tubulointerstitial inflammation and fibrosis that predict the decline of renal function. Nephrosclerosis is a major cause of renal insufficiency in blacks of African descent with a severe, early form of renovasculopathy and a rapid course to renal failure with predominant lesions of FSGS. It seems that in blacks, separate genetic factors independently lead to vascular lesions and to hypertension with a different time-scale of their onset and of their progression, nephroangiosclerosis preceding the onset of hypertension. Conversely, true and histologically identified nephrosclerosis in white Europeans rarely leads to end-stage renal disease in the absence of malignant hypertension. Various animal models demonstrate that renal vascular lesions may exist in the absence of hypertension. These experiments also point to a major role of angiotensin II and of a number of independent and overlapping cellular and molecular pathways in a cascade of inflammatory events that end in renal fibrosis. Two pathophysiologic mechanisms are at work in inducing glomerular lesions and tubulointerstitial fibrosis: a loss of autoregulation of the renal blood flow caused by an arteriolohyalinosis of the glomerular afferent arteriole and ischaemia that fosters the generation of hypoxia inducible-fibrosing factors. Not all antihypertensive drugs equally protect the kidney from nephrosclerosis. Angiotensin II antagonists exert a favourable effect on hyperfiltration. Conversely, dihydropyridine calcium-channel blockers and vasodilators do not withstand the derangement of renal autoregulation.
Topics: Humans; Hypertension; Nephrosclerosis; Risk Factors
PubMed: 25488894
DOI: 10.1093/ndt/gfu366 -
Clinical Kidney Journal Apr 2015Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential...
Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential to yield its crystalline precipitation in urine and renal interstitial tissues, leading to crystalluria, urolithiasis, acute kidney injury (AKI) or chronic kidney disease (CKD). In epidemiological studies, atazanavir/ritonavir alone or in combination with tenofovir has been associated with increased risk of progression to CKD. However, renal biopsies were not provided in these studies. Case reports showing an association between atazanavir use and tubulointerstitial nephritis among HIV-infected individuals provide clues as to the potential causes of atazanavir nephrotoxicity. We now review atazanavir-related kidney disease including urolithiasis, renal dysfunction and interstitial nephritis and illustrate the review with a further case of atazanavir-associated kidney injury with sequential renal biopsies. There are two forms of atazanavir-associated tubulointerstitial nephritis: acute tubulointerstitial nephritis that may develop AKI rapidly (in weeks) after initiation of atazanavir, and chronic tubulointerstitial nephritis that may develop progressive CKD slowly (in years) with granuloma and intrarenal precipitation of atazanavir crystals as well as crystalluria. Caution should be exercised when prescribing atazanavir to patients at high risk of CKD, and therapy should be reevaluated if renal function deteriorates, especially associated with crystalluria and hematuria.
PubMed: 25815168
DOI: 10.1093/ckj/sfv015 -
Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals.Journal of Cerebral Blood Flow and... Jan 2017Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National...
Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor.
Topics: Aged; Aged, 80 and over; Aging; Arteriolosclerosis; Brain; Cerebrovascular Circulation; Cognition; Databases, Factual; Genetic Variation; Humans; Hypertension; Risk Factors; Sulfonylurea Receptors
PubMed: 26738751
DOI: 10.1177/0271678X15621574 -
Internal Medicine (Tokyo, Japan) 2007Adiponectin has attracted great attention because of its anti-atherogenic properties; however, to date the relationship between serum adiponectin and arteriolosclerosis... (Comparative Study)
Comparative Study
OBJECTIVE
Adiponectin has attracted great attention because of its anti-atherogenic properties; however, to date the relationship between serum adiponectin and arteriolosclerosis has not been reported. In our study, we aimed to examine whether or not serum adiponectin levels are associated with arteriolosclerosis in patients with IgA nephropathy which is the most common form of chronic glomerulonephritis.
MATERIALS AND METHODS
We enrolled 35 patients aged 35.0+/-14.6, who underwent renal biopsy from August 2004 to February 2006 in our hospital, and were confirmed to have IgA nephropathy. We examined serum adiponectin, high-sensitive C-reactive protein, total cholesterol and triglyceride level, urinary protein excretion, body mass index (BMI), and the presence of arteriolosclerosis in the renal specimens. Since the serum adiponectin level is strongly affected by renal function, we classified the patients by creatinine clearance.
RESULTS
Multiple regression analysis showed the associations of adiponectin with creatinine clearance (p<0.001), BMI (p<0.001), serum triglyceride (p=0.001) and urinary protein excretion (p=0.001). We observed a positive relation of adiponectin with urinary protein excretion and an inverse relation of adiponectin with creatinine clearance, serum triglyceride, and BMI. We could not detect any relation between the presence of arteriolosclerosis and adiponectin in the IgA nephropathy patients as a whole; however, in patients whose creatinine clearance was 90-120 ml/min/1.73 m2, the serum adiponectin level of patients with arteriolosclerosis was lower than in those without arteriolosclerosis (p=0.025).
CONCLUSION
The serum level of adiponectin was related to arteriolosclerosis in IgA nephropathy patients whose renal function was almost normal. Adiponectin may prevent renal arteriolosclerosis.
Topics: Adiponectin; Adult; Arteriolosclerosis; Biomarkers; Female; Glomerulonephritis, IGA; Humans; Kidney; Male; Middle Aged
PubMed: 17443034
DOI: 10.2169/internalmedicine.46.6332 -
Advances in Chronic Kidney Disease Nov 2012Over the past century, uric acid has been considered a possible risk factor for hypertension and cardiovascular disease. However, only in the past decade, animal models...
Over the past century, uric acid has been considered a possible risk factor for hypertension and cardiovascular disease. However, only in the past decade, animal models and clinical trials have supported a more mechanistic link. Results from animal models suggest a 2-phase mechanism for the development of hyperuricemic hypertension in which uric acid induces acute vasoconstriction by activation of renin-angiotensin system, followed by uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis. This acute hypertension remains uric acid dependent and sodium independent, whereas the chronic hypertension becomes uric acid independent and sodium dependent. Small clinical trials, performed in adolescents with newly diagnosed essential hypertension, demonstrate that reduction of serum uric acid can reduce blood pressure. Although more research is clearly necessary, the available data suggest that uric acid is likely causative in some cases of early onset hypertension.
Topics: Adolescent; Animals; Disease Models, Animal; Humans; Hypertension; Hyperuricemia; Rats; Risk Factors; Uric Acid
PubMed: 23089272
DOI: 10.1053/j.ackd.2012.05.009 -
A.M.A. Archives of Internal Medicine Aug 1952
Topics: Arteries; Arteriolosclerosis; Arteriosclerosis; Cardiovascular System; Disease; Pulmonary Artery
PubMed: 14943296
DOI: 10.1001/archinte.1952.00240080023003 -
Zentralblatt Fur Chirurgie Oct 2015Martorell hypertensive ischaemic leg ulcer (HYTILU) represents an important differential diagnosis of painful leg ulcerations. Stenotic subcutaneous arteriolosclerosis... (Review)
Review
Martorell hypertensive ischaemic leg ulcer (HYTILU) represents an important differential diagnosis of painful leg ulcerations. Stenotic subcutaneous arteriolosclerosis in patients with long-standing arterial hypertension finally leads to skin infarction. The typical histological changes are very similar in Martorell HYTILU and calciphylaxis. This raises the hypothesis that the two entities may have a common pathogenesis. Martorell HYTILU presents as an extremely painful ulcer that is regularly located at the laterodorsal lower leg or at the Achilles tendon. Because of its inflammatory and violaceous wound edges and its tendency to progression, clinicians unaware of the diagnosis Martorell HYTILU might misdiagnose pyoderma gangrenosum or necrotising cutaneous vasculitis start an immunosuppressive treatment and avoid surgical diagnostic and therapeutic procedures. Instead, necrosectomy and split skin grafting are the treatment of choice for Martorell HYTILU.
Topics: Debridement; Diagnosis, Differential; Humans; Hypertension; Ischemia; Leg; Leg Ulcer; Surgical Flaps
PubMed: 25333521
DOI: 10.1055/s-0034-1382898 -
PLOS Digital Health Jan 2023The morphological feature of retinal arterio-venous crossing patterns is a valuable source of cardiovascular risk stratification as it directly captures vascular health....
The morphological feature of retinal arterio-venous crossing patterns is a valuable source of cardiovascular risk stratification as it directly captures vascular health. Although Scheie's classification, which was proposed in 1953, has been used to grade the severity of arteriolosclerosis as diagnostic criteria, it is not widely used in clinical settings as mastering this grading is challenging as it requires vast experience. In this paper, we propose a deep learning approach to replicate a diagnostic process of ophthalmologists while providing a checkpoint to secure explainability to understand the grading process. The proposed pipeline is three-fold to replicate a diagnostic process of ophthalmologists. First, we adopt segmentation and classification models to automatically obtain vessels in a retinal image with the corresponding artery/vein labels and find candidate arterio-venous crossing points. Second, we use a classification model to validate the true crossing point. At last, the grade of severity for the vessel crossings is classified. To better address the problem of label ambiguity and imbalanced label distribution, we propose a new model, named multi-diagnosis team network (MDTNet), in which the sub-models with different structures or different loss functions provide different decisions. MDTNet unifies these diverse theories to give the final decision with high accuracy. Our automated grading pipeline was able to validate crossing points with precision and recall of 96.3% and 96.3%, respectively. Among correctly detected crossing points, the kappa value for the agreement between the grading by a retina specialist and the estimated score was 0.85, with an accuracy of 0.92. The numerical results demonstrate that our method can achieve a good performance in both arterio-venous crossing validation and severity grading tasks following the diagnostic process of ophthalmologists. By the proposed models, we could build a pipeline reproducing ophthalmologists' diagnostic process without requiring subjective feature extractions. The code is available (https://github.com/conscienceli/MDTNet).
PubMed: 36812612
DOI: 10.1371/journal.pdig.0000174 -
Nephrology, Dialysis, Transplantation :... Feb 1999
Topics: Arterioles; Arteriosclerosis; Cocaine; Female; Humans; Kidney; Kidney Failure, Chronic; Middle Aged; Renal Artery; Renal Circulation
PubMed: 10069205
DOI: 10.1093/ndt/14.2.434