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1.
Cellular Stress and Molecular Responses in Bladder Ischemia.
Yang, JH, Choi, HP, Niu, W, Azadzoi, KM
International journal of molecular sciences. 2021;(21)
Abstract
The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity. Recent studies imply a central role of cellular energy sensors, cellular stress sensors, and stress response molecules in bladder responses to ischemia. The cellular energy sensor adenosine monophosphate-activated protein kinase was shown to play a role in detrusor overactivity and neurodegeneration in bladder ischemia. The cellular stress sensors apoptosis signal-regulating kinase 1 and caspase-3 along with heat shock proteins were characterized as important contributing factors to smooth muscle structural modifications and apoptotic responses in bladder ischemia. Downstream pathways seem to involve hypoxia-inducible factor, transforming growth factor beta, vascular endothelial growth factor, and nerve growth factor. Molecular responses to bladder ischemia were associated with differential protein expression, the accumulation of non-coded amino acids, and post-translational modifications of contractile proteins and stress response molecules. Further insight into cellular stress responses in bladder ischemia may provide novel diagnostic and therapeutic targets against LUTS.
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2.
Ischemia-Modified Albumin: Origins and Clinical Implications.
Shevtsova, A, Gordiienko, I, Tkachenko, V, Ushakova, G
Disease markers. 2021;:9945424
Abstract
Albumin is one of the most abundant proteins in the body of mammals: about 40% of its pool is located in the intravascular space and the remainder is found in the interstitial space. The content of this multifunctional protein in blood is about 60-65% of total plasma proteins. A decrease in its synthesis or changes of functional activity can destabilize oncotic blood pressure, cause a violation of transporting hormones, fatty acids, metals, and drugs. Albumin properties change under ischemic attacks associated with oxidative stress, production of reactive oxygen species, and acidosis. Under these conditions, ischemia-modified albumin (IMA) is generated that has a reduced metal-binding capacity, especially for transition metals, such as copper, nickel, and cobalt. The method of determining the cobalt-binding capability of HSA was initially proposed to evaluate IMA level and then licensed as an ACB test for routine clinical analysis for myocardial ischemia. Subsequent studies have shown the viability of the ACB test in diagnosing other diseases associated with the development of oxidative stress. This review examines recent data on IMA generation mechanisms, describes principles, advantages, and limitations of methods for evaluation of IMA levels, and provides detailed analysis of its use in diagnostic and monitoring therapeutic efficacy in different diseases.
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3.
Use of OCTA, FA, and Ultra-Widefield Imaging in Quantifying Retinal Ischemia: A Review.
Or, C, Sabrosa, AS, Sorour, O, Arya, M, Waheed, N
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018;(1):46-51
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Abstract
As ischemia remains a key prognostic factor in the management of various diseases including diabetic retinopathy, an increasing amount of research has been dedicated to its quantification as a potential biomarker. Advancements in the quantification of retinal ischemia have been made with the imaging modalities of fluorescein angiography (FA), ultra-widefield imaging (UWF), and optical coherence tomography angiography (OCTA), with each imaging modality offering certain benefits over the others. FA remains the gold standard in assessing the extent of ischemia. UWF imaging has allowed for the assessment of peripheral ischemia via FA. It is, however, OCTA that offers the best visualization of retinal vasculature with its noninvasive depth-resolved imaging and therefore has the potential to become a mainstay in the assessment of retinal ischemia. The primary purpose of this article is to review the use of FA, UWF, and OCTA to quantify retinal ischemia and the various methods described in the literature by which this is achieved.
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4.
Raynaud's Syndrome: a neglected disease.
Poredos, P, Poredos, P
International angiology : a journal of the International Union of Angiology. 2016;(2):117-21
Abstract
Raynaud's Syndrome is a frequent manifestation of digital ischemia which occurs or is aggravated upon exposure to cold temperatures or emotional distress. Primary Raynaud is a benign disease which predominantly affects younger women and is transient without serious sequelae. In contrast, secondary Raynaud is usually one of the manifestations of systemic disease and is, in addition to symptoms of the basic disease, associated with ischemic lesions. The diagnosis of primary Raynaud is mostly based on the clinical presentation. In secondary Raynaud, additional investigating techniques including imaging investigations and laboratory tests for the detection of underline disease are needed. Treatment is based on lifestyle modification, which includes smoking cessation, avoiding low outside temperatures, avoiding the use of vibrating tools and limiting repeated hand actions. Drug treatment consists of calcium-channel blockers, nitroglycerine ointments, prostacyclins and various new drugs such as endothelin receptor antagonists, phosphodiesterase inhibitors and serotonin receptor antagonists. Most of these drugs are effective in less than 50% of treated patients and do not completely abolish vasospastic attacks, but reduce the severity and frequency of attacks. The prostacyclin derivate iloprost is the most promising drug in the management of secondary Raynaud's disease. Other therapeutic procedures including chemical or surgical sympathectomy are obsolete and without any long-term positive effects.
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5.
Paracentral acute middle maculopathy spectral-domain optical coherence tomography feature of deep capillary ischemia.
Rahimy, E, Sarraf, D
Current opinion in ophthalmology. 2014;(3):207-12
Abstract
PURPOSE OF REVIEW To describe the novel spectral-domain optical coherence tomography (SD-OCT) finding of paracentral acute middle maculopathy (PAMM) that can be associated with acute macular neuroretinopathy (AMN) or retinal vasculopathy, and that may indicate an underlying pathogenesis related to ischemia of the retinal deep capillary plexus (DCP). RECENT FINDINGS With the advent of high-definition SD-OCT imaging, we are now able to detect deep capillary ischemia. Although cotton wool spots are caused by ischemia of the superficial capillary plexus, PAMM is caused by ischemia of the DCP, and appears as hyper-reflective, band-like lesions in the middle retina, extending from the inner nuclear layer (INL)/outer plexiform layer junction to involve the full-thickness INL. Over time, these lesions resolve with atrophy of the INL, resulting in persistent paracentral scotomas for the patient. Originally, PAMM was identified in isolation and thus classified into a subcategory of AMN. Subsequent reports have demonstrated PAMM lesions in the setting of coexisting retinal vascular disease, notably nonproliferative diabetic retinopathy and central retinal vein occlusion. SUMMARY PAMM refers to a recently described class of characteristic SD-OCT lesions involving the middle layers of the retina at the level of the INL. If a patient presenting with PAMM is young and healthy without any other vascular disease, this may represent a novel variant of AMN. However, if the patient has an underlying retinal vascular disease, such as diabetic retinopathy or retinal vascular occlusion, one would refer to the lesion as PAMM complicating the underlying retinal vascular disease.
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6.
Sickle cell retinopathy: diagnosis and treatment.
Bonanomi, MT, Lavezzo, MM
Arquivos brasileiros de oftalmologia. 2013;(5):320-7
Abstract
Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.
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7.
Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?
Fernández-Ruiz, J, Sagredo, O, Pazos, MR, García, C, Pertwee, R, Mechoulam, R, Martínez-Orgado, J
British journal of clinical pharmacology. 2013;(2):323-33
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Abstract
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9)-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9)-tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
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8.
Scorpion venoms, kidney and potassium.
Angsanakul, J, Sitprija, V
Toxicon : official journal of the International Society on Toxinology. 2013;:81-7
Abstract
Scorpion venoms cause renal injury by the interaction of renal ischemia due to intense renal vasoconstriction and inflammatory reactions due to proinflammatory cytokines and mediators. Renal vasoconstriction is not only induced by catecholamine storm but also by angiotensin II and the direct action of venom on vascular ion channels. Increased aldosterone also contributes to hypertension. Blocking of renal tubular K channels decreases renal K excretion and increases serum K level which increases aldosterone release. Hyperaldosteronism increases K excretion mostly through ROMK2 and ROMK3 unblocked by the venom. The presence of angiotensin converting enzyme inhibitor in some scorpion species can increase serum K. Therefore, there are both K increasing and K decreasing effects in renal K excretion. Serum K in scorpionism is the net result of the two opposing effects. Hyperkalemia is therefore inconsistent.
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9.
Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease?
Manousaridis, K, Talks, J
The British journal of ophthalmology. 2012;(2):179-84
Abstract
Anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to be effective at improving vision in patients with macular oedema due to diabetic retinopathy and vein occlusions, but blocking VEGF at least in theory could be detrimental to vascular integrity. For this reason, some patients with macular ischaemia were excluded from studies showing the effectiveness of therapy. A considerable number of patients present with mixed pathology of macular oedema and macular ischaemia and it is often impossible to determine the degree to which ischaemia accounts for decreased vision. In this review, the authors have dealt with the specific question of whether or not there is evidence to support potential worsening of the macular perfusion and visual function after anti-VEGF treatment with bevacizumab or ranibizumab for macular oedema secondary to diabetic retinopathy or retinal vein occlusions, especially if there is coexisting macular ischaemia. The authors conclude that anti-VEGF therapy rarely seems to further compromise the retinal circulation; however, worsening of macular ischaemia in the long term cannot be definitely excluded, particularly in eyes with significant ischaemia at baseline and after repeated intraocular anti-VEGF injections. The decision to offer prolonged anti-VEGF treatment in cases of significant coexisting macular ischaemia should not be based only on measurements of macular thickness; instead repeat fluorescein angiograms should be performed.
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10.
[Nutrition in intestinal failure after intestinal ischemia].
Ellegård, L
Lakartidningen. 2012;(49-50):2294-5