Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice

Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothe- sis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overac- tive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipra- mine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and nor- adrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory ef- fect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition

The role of sirtuins and uncoupling proteins on vascular aging: The Northern Manhattan Study experience

aging affects all organs. arteries, in particular, are among the most affected. Vascular aging (VA) is defined as age-associated changes in function and structure of vessels. classical VA phenotypes are carotid intima-media thickness (IMT), carotid plaque (CP), and arterial stiffness (STIFF). Individuals have different predisposition to these VA phenotypes and their associated risk of cardiovascular events. some develop an early vascular aging (EVA), and others are protected and identified as having supernormal vascular aging (SUPERNOVA). the mechanisms leading to these phenotypes are not well understood. In the northern manhattan study (NOMAS), we found genetic variants in the 7 sirtuins (SIRT) and 5 uncoupling Proteins (UCP) to be differently associated with risk to developing VA phenotypes. In this article, we review the results of genetic-epidemiology studies to better understand which of the single nucleotide polymorphisms (SNPs) in SIRT and UCP are responsible for both EVA and SUPERNOVA

A Novel Anti-Inflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia

Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vascular diseases, such as stroke and myocardial infarction. The relationship between atherosclerosis and risk of neurodegeneration has been established, in particular with vascular cognitive impairment and dementia (VCID). Systemic atherosclerosis increases the risk of VCID by inducing cerebral infarction, or through systemic or local inflammatory factors that underlie both atherosclerosis and cognition. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are involved in inflammatory processes, but with opposite roles. Specifically, omega-3 PUFAs exert anti-inflammatory properties by competing with omega-6 PUFAs and displacing arachidonic acid in membrane phospholipids, decreasing the production of pro-inflammatory eicosanoids. Experimental studies and some clinical trials have demonstrated that omega-3 PUFA supplementation may reduce the risk of different phenotypes of atherosclerosis and cardiovascular disease. This review describes the link between atherosclerosis, VCID and inflammation, as well as how omega-3 PUFA supplementation may be useful to prevent and treat inflammatory-related diseases

Intracerebral Venous System: Monitoring by Transcranial Color-Coded Duplex Sonography (TCCS)

Transcranial Doppler and transcranial color-coded duplex sonography (TCCS) have been less utilized for the assessment of the intracerebral venous system although they are widely used imaging modalities for examinations of the cerebral arterial system. This is partially due to early technical limitations of ultrasound systems as well as a low prevalence of clinical cerebral venous disease to evaluate the reliability of these ultrasound technologies. Although venous TCCS is not currently used in routine clinical practice, it has a great potential to be a quick and complementary bedside diagnostic and monitoring modality for the patients with cerebral venous sinus thrombosis, arteriovenous malformations, malignant ischemic stroke, subarachnoid hemorrhage, and instability of intracranial pressure. In this chapter, we review cerebral venous anatomy, venous TCCS investigation technique, and clinical applications of TCCS in the intracerebral venous system

Topography of Vertebral Artery Origin Plaques: Characteristics and Determinants

Atherosclerotic plaques located at the vertebral artery ostium (VAo) are a mechanism for posterior circulation stroke, but little is known about VAo plaque topography and formation. In this study, we describe the topography of atherosclerotic plaques involving the origin of the vertebral artery (VA). Cross-sectional analyses of extracranial duplex studies were performed, and VAo plaques were classified based on their topography in 3 groups: (1) exclusively at the VA ostium; (2) predominantly subclavian, with extension into the vertebral ostium; and (3) predominantly ostial, with extension into the subclavian artery). Chi-square and analysis of variance tests were performed to investigate the association between VAo plaque topography and continuous and categorical variables, respectively. A total of 99 of 481 (21%) ultrasound duplex studies showed VAo plaques. The majority of the plaques (60%) were found to extend from the subclavian to the ostium. Plaques occurred more frequently at the medial wall of the VAo. No vascular risk factors were associated with plaque formation; however, women were more likely to have plaques involving predominantly or exclusively the VAo (P = .004). We describe 3 different patterns of VAo involvement in patients with ostial atherosclerotic VA disease. VAo plaques occurred almost exclusively at the medial wall of the vessel. Women had more plaques involving predominantly the origin. Prospective studies are needed to investigate the clinical significance of these findings

Design and Usability Testing of the Stroke Caregiver Support System: A Mobile-Friendly Website to Reduce Stroke Caregiver Burden

Purpose The purpose of this study was to design a mobile-friendly, Internet-based website, modeled on previously described websites for Alzheimer caregivers, to equip stroke caregivers and potentially reduce caregiver burden. Design A mixed-methods study was performed to design and test the usability of the Stroke Caregiver Support System (SCSS). Methods An iterative, user-centered design approach was employed in three phases: (I) Focus Groups, (II) Structured Interviews, and (III) Usability Testing. Phase I and Phase II provided information for the development of the SCSS website, whereas Phase III helped in gathering data regarding the usability and efficacy of the newly implemented SCSS website. Findings Qualitative data on caregiving and the content and design of the SCSS were obtained from focus groups and interviews. In the usability test, the nine caregivers who completed Phase III (78% women, mean age = 46, SD = 17) exhibited a high level of burden and depressive symptoms (median [Q1, Q3] Zarit burden score = 18 [16, 23], Center of Epidemiologic Studies-Depression Scale = 15 [8, 17]). Caregivers conveyed the usability of the SCSS but also expressed several needed improvements. Conclusions Participants reported the value of the SCSS, but further refinements are needed to maximize its usability and potential efficacy. Clinical Relevance The SCSS has potential to reduce caregiver burden in stroke

Abstract WP419: Effect of Race-Ethnicity and Ct Angiography on Acute Kidney Injury During Blood Pressure Treatment for Intracerebral Hemorrhage

Background: Lowering blood pressure intensively in acute intracerebral hemorrhage (ICH) is associated with acute kidney injury (AKI). Blacks have a higher incidence of ICH as well as kidney disease. In addition, CT angiography (CTA), which may also be associated with AKI, is often done in acute ICH. Our objective was to investigate the relationship between aggressive BP management, CTA, race ethnicity and the risk of developing AKI in patients presenting with ICH. Methods: Patients with spontaneous ICH hospitalized in 2017 and 2018 were included. Patients with underlying arteriovenous malformations, brain metastases, and aneurysms, were excluded. We calculated the difference between the highest and lowest systolic blood pressure (SBP) during the first 24 hours of admission. Creatinine levels at admission were compared to the highest creatinine during the first 7 days after admission. AKI was defined as absolute increase in creatinine of >0.3 or 50% increase from baseline creatinine. Linear regression models were used to assess the association between SBP difference, history of CTA and AKI. Results: A total of 289 patients were included (mean±SD age 63±13), 40% were women, 41% Hispanics and 47% blacks. The majority of the patients underwent CTA (71%). The prevalence of AKI was high (30%). Blacks showed a significantly higher SBP compared to whites and Hispanics (p=.02), but no difference was found in AKI incidence (33% in Blacks vs. 27% in Caucasians and Hispanics (p=0.7). Higher BUN, creatinine and SBP on admission were associated with AKI (p=.001, p<.0001, and p=.0001, respectively). Those who developed AKI had a greater mean drop of SBP in 24 hours compared to those who did not (103mmHg vs. 84mmHg, p=.0007) and a higher prevalence of diabetes (p=.0013). In fully adjusted models, AKI was associated with SBP drop (p=.0003), but not with race/ethnicity (p=.6) or CTA (p=.06). Conclusion: We confirm, in a real-life ICH population, the association between intense blood pressure lowering and development of AKI. Race/ ethnicity and CTA were not independently associated with AKI. Our findings do not suggest that obtaining a CTA in acute ICH poses significant additional risks on developing AKI

Effect of Race-Ethnicity and CT Angiography on Renal Injury During Blood Pressure Treatment for Intracerebral Hemorrhage

Lowering blood pressure intensively in acute intracerebral hemorrhage (ICH) is associated with adverse renal events; Blacks and Hispanics have a higher incidence of ICH and kidney disease than Whites. In addition, CT angiography (CTA), which may also be associated with acute kidney injury (AKI), is often done in acute ICH. Our objective was to investigate the relationship between aggressive BP management, CTA, race-ethnicity and the risk of developing AKI in patients presenting with ICH. We retrospectively calculated the difference between the highest and lowest systolic blood pressure during the first 24 h of admission in patients with spontaneous ICH over 30 months. Creatinine (Cr) levels at admission were compared to the highest Cr level during the first 7 days after admission. AKI was defined as any > 50% increase of baseline Cr during the first 7 days. Logistic regression models were used to assess the association between race-ethnicity and CTA and AKI. We also analyzed the incidence of AKI stratified by race-ethnicity. A total of 394 patients were included (mean age ± SD 63 ± 14 years), 160 patients (41%) were women, 162 (41%) Hispanic, 39 (10%) White and 189 (48%) Black. Most of the patients underwent CTA (73%). The prevalence of AKI was (18%), but no difference was found in AKI incidence (19% in Blacks vs. 17% in Whites vs. 18% in Hispanics (p = 0.940). In fully adjusted models, AKI was not associated with race-ethnicity (p = 0.665) or CTA (p = 0.187). The stratified analysis by race-ethnicity did not change our findings. We found no association between race-ethnicity or CTA and AKI during the acute management of ICH in a real-life stroke population. Our findings suggest that CTA can be safely obtained in acute ICH, even in populations of diverse race-ethnicity who may be more prone to adverse kidney events. CTA did not contribute to developing AKI