scholarly journals Spontaneous and Drug-induced Arteritis/Polyarteritis in the Göttingen Minipig—Review

2018 ◽  
Vol 46 (2) ◽  
pp. 121-130 ◽  
Author(s):  
Zuhal Dincer ◽  
Virginie Piccicuto ◽  
Ursula Junker Walker ◽  
Andreas Mahl ◽  
Sean McKeag
Keyword(s):  
Spinal Cord ◽  
Urinary Bladder ◽  
Blood Vessels ◽  
Polyarteritis Nodosa ◽  
Pain Syndrome ◽  
Vascular Changes ◽  
Drug Induced ◽  
Göttingen Minipig ◽  
Age Related ◽  
Immune Mediated

Arteritis/polyarteritis occurs spontaneously in many species used in preclinical toxicology studies. In Göttingen minipigs, arteritis/polyarteritis is an occasionally observed background change. In the minipig, this finding differs in frequency and nature from age-related polyarteritis nodosa in rats or monkeys, and Beagle pain syndrome in dogs. In minipigs, it can be present in a single small- or medium-sized artery of an organ or a few organs and is most commonly recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. The etiology is unknown although it has been considered in minipigs as well as in rats, dogs, and monkeys to be possibly immune mediated. This background change is important with respect to its nature and distribution in the minipig in order to distinguish it from drug-induced vascular changes, which might occur in similar locations and have similar morphologic features. This review summarizes the morphology, incidence, and predilection sites of arteritis as a spontaneously occurring background change and as a drug-induced vasculopathy in the minipig, and also describes the main aspects to consider when evaluating vascular changes in Göttingen minipig toxicity studies and their human relevance.

scholarly journals Age-related changes in the nervous apparatus of the blood vessels in the spinal cord

2013 ◽  
Vol 17 (3 (67) p.1) ◽  
pp. 122-124
Author(s):  
Yu. I. Pigolkin ◽  
G. V. Zolotenkova
Keyword(s):  
Spinal Cord ◽  
Blood Vessels ◽  
Practical Work ◽  
Biological Age ◽  
Postnatal Ontogenesis ◽  
Nervous Apparatus ◽  
Age Related ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Age Related Changes

This paper was designed to study changes in the nervous apparatus of the blood vessels in the spinal cord with a view to determining the biological age of man. The pial and intramedullary vascular systems of the brain and spinal cord were examined in different periods of postnatal ontogenesis (between the age of 1 to 90 years). The data obtained on the age-related rearrangement of the nervous apparatus of the spinocerebral arterial vessels can also be used for the solution of practical problems encountered in the practical work of forensic medical experts.

scholarly journals A critical role for microglia in maintaining vascular integrity in the hypoxic spinal cord

2019 ◽  
Vol 116 (51) ◽  
pp. 26029-26037 ◽  
Author(s):  
Sebok K. Halder ◽  
Richard Milner
Keyword(s):  
Spinal Cord ◽  
Cord Blood ◽  
Blood Vessels ◽  
Critical Role ◽  
Barrier Properties ◽  
Vascular Leak ◽  
Vascular Integrity ◽  
Age Related ◽  
Obstructive Sleep ◽  
The Impact

Hypoxic preconditioning reduces disease severity in a mouse model of multiple sclerosis (MS), in part by enhancing the barrier properties of spinal cord blood vessels. Because other studies have shown that similar levels of hypoxia transiently increase permeability of central nervous system (CNS) blood vessels, the goal of this study was to define the impact of chronic mild hypoxia (CMH, 8% O2) on the integrity of spinal cord blood vessels and the responses of neighboring glial cells. Using extravascular fibrinogen as a marker of vascular disruption, we found that CMH triggered transient vascular leak in spinal cord blood vessels, particularly in white matter, which was associated with clustering and activation of Mac-1–positive microglia around disrupted vessels. Microglial depletion with the colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX5622, while having no effect under normoxic conditions, profoundly increased vascular leak in both white and gray matter during CMH, and this was associated with disruption of astrocyte-vascular coupling and enhanced loss of tight junction proteins. Microglial repair of leaky blood vessels was blocked by a peptide that inhibits the interaction between fibrinogen and its Mac-1 integrin receptor. These findings highlight an important role for microglia in maintaining vascular integrity in the hypoxic spinal cord and suggest that a fibrinogen–Mac-1 interaction underpins this response. As relative hypoxia is experienced in many situations including high altitude, lung disease, obstructive sleep apnea, and age-related CNS ischemia/hypoxia, our findings have important implications regarding the critical role of microglia in maintaining vascular integrity in the CNS.

Measuring renal function in old age

2008 ◽  
Vol 18 (4) ◽  
pp. 257-267
Author(s):  
Sanghamitra Chakrabarti ◽  
Indrajit Chattopadhyay
Keyword(s):  
Renal Function ◽  
Old Age ◽  
Renal Stones ◽  
Renal Tubules ◽  
Older Individuals ◽  
Vascular Changes ◽  
Drug Induced ◽  
Functional Changes ◽  
Age Related ◽  
Tract Infections

Accurate assessment of renal function is vital, especially in older individuals, as this is the population in which the greatest burden of chronic kidney disease (CKD) occurs. With ageing, the kidneys undergo a multitude of structural and functional changes. The age-related changes in the kidneys may be further complicated by concurrent pre-renal, renal and post-renal factors common in old age, such as hypertensive glomerulosclerosis, diabetic nephropathy, congestive cardiac failure, renovascular atheroma, urinary outflow obstruction, urinary tract infections, renal stones and drug-induced nephrotoxicity. Structurally, there is a progressive loss of predominantly cortical renal mass, a decrease in the number of glomeruli, an increase in the proportion of sclerotic glomeruli, tubulo-interstitial changes resulting in fibrosis and atrophy, arteriosclerotic vascular changes and a reduction in renal blood flow. Excretory and reabsorptive capacities of the renal tubules may also decline with ageing. Functionally, although there may be a decline in the glomerular filtration rate (GFR) resulting primarily from a reduction in the number of functioning nephrons, this decline may not be universal. Up to a third of elderly people may not demonstrate a decline in GFR with ageing, whilst in some individuals GFR may actually increase with age.

Bioelectrodes for Neural Prostheses

1985 ◽  
Vol 55 ◽  
Author(s):  
F. Terry Hambrecht
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Urinary Bladder ◽  
Cochlear Implants ◽  
Neural Prostheses ◽  
The Future ◽  
Spinal Cord Disorders ◽  
The Central Nervous System ◽  
Auditory Prostheses

ABSTRACTNeural prostheses which are commercially available include cochlear implants for treating certain forms of deafness and urinary bladder evacuation prostheses for individuals with spinal cord disorders. In the future we can anticipate improvements in bioelectrodes and biomaterials which should permit more sophisticated devices such as visual prostheses for the blind and auditory prostheses for the deaf based on microstimulation of the central nervous system.

scholarly journals Investigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury

2021 ◽  
Author(s):  
Yanshan Cao ◽  
Ahsan Bairam ◽  
Alison Jee ◽  
Ming Liu ◽  
Jack Uetrecht
Keyword(s):  
Liver Injury ◽  
Skin Rash ◽  
Covalent Binding ◽  
Reactive Metabolites ◽  
Important Data ◽  
Drug Induced ◽  
Interindividual Differences ◽  
Immune Mediated ◽  
Sulfate Conjugate

Abstract Trimethoprim (TMP)-induced skin rash and liver injury are likely to involve the formation of reactive metabolites. Analogous to nevirapine-induced skin rash, one possible reactive metabolite is the sulfate conjugate of α-hydroxyTMP, a metabolite of TMP. We synthesized this sulfate and found that it reacts with proteins in vitro. We produced a TMP-antiserum and found covalent binding of TMP in the liver of TMP-treated rats. However, we found that α-hydroxyTMP is not a substrate for human sulfotransferases, and we did not detect covalent binding in the skin of TMP-treated rats. Although less reactive than the sulfate, α-hydroxyTMP was found to covalently bind to liver and skin proteins in vitro. Even though there was covalent binding to liver proteins, TMP did not cause liver injury in rats or in our impaired immune tolerance mouse model that has been able to unmask the ability of other drugs to cause immune-mediated liver injury. This is likely because there was much less covalent binding of TMP in the livers of TMP-treated mice than TMP-treated rats. It is possible that some patients have a sulfotransferase that can produce the reactive benzylic sulfate; however, α-hydroxyTMP, itself, has sufficient reactivity to covalently bind to proteins in the skin and may be responsible for TMP-induced skin rash. Interspecies and interindividual differences in TMP metabolism may be one factor that determines the risk of TMP-induced skin rash. This study provides important data required to understand the mechanism of TMP-induced skin rash and drug-induced skin rash in general.

scholarly journals Immune-Mediated Drug-Induced Liver Injury: Immunogenetics and Experimental Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4557
Author(s):  
Alessio Gerussi ◽  
Ambra Natalini ◽  
Fabrizio Antonangeli ◽  
Clara Mancuso ◽  
Elisa Agostinetto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Experimental Models ◽  
Clinical Event ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated ◽  
Liver Injuries ◽  
Immunological Mechanisms ◽  
Molecular Aspects ◽  
Therapeutic Tools

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

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