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International Journal of Molecular... Sep 2023Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side... (Review)
Review
Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways.
Topics: Humans; Exosomes; Stem Cells; Spinal Cord Injuries; Mesenchymal Stem Cells; Biological Transport
PubMed: 37762150
DOI: 10.3390/ijms241813849 -
Clinical Autonomic Research : Official... Dec 2023
Recent updates in autonomic research: new insights into vagal nerve activity during exercise, cardiac autonomic neuropathy and silent myocardial infarction in diabetes, and timing of orthostatic blood pressure change and future risk of dementia.
Topics: Humans; Blood Pressure; Heart; Vagus Nerve; Diabetes Mellitus; Myocardial Infarction; Dementia; Autonomic Nervous System Diseases; Diabetic Neuropathies
PubMed: 37924394
DOI: 10.1007/s10286-023-00999-x -
Journal of Neurology Nov 2023Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic... (Review)
Review
Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. Early onset and extensive autonomic dysfunction, including cardiovascular dysfunction characterized by orthostatic hypotension (OH) and supine hypertension, urinary dysfunction characterized by overactive bladder and incomplete bladder emptying, sexual dysfunction characterized by sexual desire deficiency and erectile dysfunction, and gastrointestinal dysfunction characterized by delayed gastric emptying and constipation, are the main features of MSA. Autonomic dysfunction greatly reduces quality of life and increases mortality. Therefore, early diagnosis and intervention are urgently needed to benefit MSA patients. In this review, we aim to discuss the systematic treatment of autonomic dysfunction in MSA, and focus on the current methods, starting from non-pharmacological methods, such as patient education, psychotherapy, diet change, surgery, and neuromodulation, to various drug treatments targeting autonomic nerve and its projection fibers. In addition, we also draw attention to the interactions among various treatments, and introduce novel methods proposed in recent years, such as gene therapy, stem cell therapy, and neural prosthesis implantation. Furthermore, we elaborate on the specific targets and mechanisms of action of various drugs. We would like to call for large-scale research to determine the efficacy of these methods in the future. Finally, we point out that studies on the pathogenesis of MSA and pathophysiological mechanisms of various autonomic dysfunction would also contribute to the development of new promising treatments and concepts.
Topics: Male; Humans; Multiple System Atrophy; Quality of Life; Autonomic Nervous System Diseases; Erectile Dysfunction; Parkinsonian Disorders
PubMed: 37477834
DOI: 10.1007/s00415-023-11876-y -
Hypertension (Dallas, Tex. : 1979) Jun 2024Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially...
BACKGROUND
Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension.
METHODS
Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg.
RESULTS
We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension.
CONCLUSIONS
Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.
Topics: Humans; Female; Male; Aged; Frailty; Republic of Korea; Hypertension; Hypotension, Orthostatic; Blood Pressure; Frail Elderly; Quality of Life; Aged, 80 and over; Hand Strength; Blood Pressure Determination
PubMed: 38511313
DOI: 10.1161/HYPERTENSIONAHA.123.22382 -
NPJ Parkinson's Disease Oct 2023It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the...
It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the efficacy, tolerability, and safety among anti-PD drugs from several classes in patients with fluctuating PD who received levodopa through network meta-analysis (NMA). Twelve anti-PD drugs belonging to 4 different drug classes (dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, and an adenosine A2A receptor antagonist) were selected. We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials (RCTs) comparing placebo with anti-PD drug or among anti-PD drugs in patients with PD who experienced motor fluctuations or wearing-off and received levodopa. We included 54 RCTs in the analysis. The NMA was performed under a frequentist framework using a random-effects model. The efficacy outcome was change in daily off-time, and the tolerability outcome was discontinuation due to all causes. Safety outcomes included discontinuation due to adverse events (AEs) and the incidence of AEs, dyskinesia, hallucination, and orthostatic hypotension. According to the surface under the cumulative ranking curve (SUCRA) in the NMA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in efficacy, followed by pramipexole (0.762), ropinirole extended release (ER) (0.750), and safinamide (0.691). In terms of tolerability, ropinirole (0.954) ranked the highest, followed by pramipexole (0.857), safinamide (0.717), and ropinirole ER (0.708). Each anti-PD drug had different SUCRA ranking profiles for the safety outcomes. These findings suggest that ropinirole, pramipexole, and safinamide are well-balanced anti-PD drugs that satisfy both efficacy and tolerability outcomes.
PubMed: 37853009
DOI: 10.1038/s41531-023-00589-8 -
Asian Spine Journal Aug 2023Retrospective case-control study.
STUDY DESIGN
Retrospective case-control study.
PURPOSE
To understand the prevalence of persistent orthostatic hypotension (POH), as well as its risk factors and cardiovascular pathology, in patients receiving surgery for the adult spinal deformity (ASD).
OVERVIEW OF LITERATURE
Although reports of the incidence of and risk factors for POH in different spinal disorders have recently been published, we are not aware of the comprehensive evaluation of POH following surgery for ASD.
METHODS
We examined medical records from a single central database for 65 patients receiving surgical treatment for ASD. Statistical comparisons were made between patients who experienced postoperative POH and those who did not, by examining patient and operative characteristics, such as age, sex, comorbidities, functional status, preoperative neurological function, vertebral fractures, three-column osteotomy, total operative time, estimated blood loss, length of stay, and radiographic parameters. The determinants of POH were assessed using multiple logistic regression.
RESULTS
We showed that postoperative POH was a complication of ASD surgery, with a 9% incidence rate. Patients with POH were statistically considerably more likely to require supported walkers due to partial paralysis and to have comorbidities including diabetes and neurodegenerative disease (ND). Furthermore, ND was an independent risk factor for postoperative POH (odds ratio, 4.073; 95% confidence interval, 1.094-8.362; p =0.020). Moreover, perioperative evaluation of the inferior vena cava showed that patients with postoperative POH had preoperative congestive heart failure and had hypovolemia lower postoperative diameter of the inferior vena cava than patients without POH.
CONCLUSIONS
Postoperative POH is a potential complication of ASD surgery. The most pertinent risk factor is having an ND. According to our study, patients who have surgery for ASD may experience alterations in their hemodynamics.
PubMed: 37408295
DOI: 10.31616/asj.2022.0296 -
Life Sciences in Space Research Feb 2024In view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in... (Review)
Review
In view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in space. Astronauts are exposed to several risks in space, including a protracted period of microgravity, radiation, and mechanical unloading of the body. Several deleterious effects of such an environment are reported, including orthostatic intolerance, cardiovascular endothelial dysfunction, cellular and molecular changes, and changes in the composition of the gut microbiome. Herein, the correlation between the gut microbiome and cardiovascular disease in a microgravity environment is evaluated. Additionally, the relationship between orthostatic hypotension, cardiac shrinkage and arrhythmias during spaceflight, and cellular alterations during spaceflight is reviewed. Given its impact on human health in general, modifying the gut microbiota may significantly promote astronaut health and performance. This is merited, given the prospect of augmented human activities in future space missions.
Topics: Humans; Weightlessness; Gastrointestinal Microbiome; Space Flight; Astronauts; Heart
PubMed: 38245353
DOI: 10.1016/j.lssr.2023.09.003 -
The Journals of Gerontology. Series A,... Feb 2024Falls are a common cause of injury, hospitalization, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognized risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Falls are a common cause of injury, hospitalization, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognized risk factors for falls. This systematic review assesses the association between cardiovascular disorders and falls in older adults.
METHODS
Systematic searches were conducted on MEDLINE and Embase, encompassing all literature published prior to December 31, 2022. Included studies addressed persons aged 50 years and older, and assessed the association between cardiovascular disorders and falls or the efficacy of cardiovascular-based interventions to reduce falls. Two reviewers independently extracted data and assessed study quality utilizing a modified Newcastle-Ottawa scale for observational studies, and the Cochrane Risk of Bias 2 tool for interventional studies. A systematic narrative analysis of all cardiovascular outcomes, and meta-analyses of unadjusted odds ratios (ORs) were performed.
RESULTS
One hundred and eighty-four studies were included: 181 observational and 3 interventional. Several cardiovascular disorders, including stroke, coronary artery disease, valvular heart disease, arterial stiffness, arrhythmia, orthostatic hypotension, and carotid sinus hypersensitivity, were consistently associated with falls. In meta-analysis of unadjusted ORs, the largest positive pooled associations with falls during a 12-month reporting interval were for stroke (OR: 1.90, 95% confidence interval [CI]: 1.70-2.11), peripheral arterial disease (OR: 1.82, 95% CI: 1.12-2.95), atrial fibrillation (OR: 1.52, 95% CI: 1.27-1.82), and orthostatic hypotension (OR: 1.39, 95% CI: 1.18-1.64).
CONCLUSIONS
Several cardiovascular disorders are associated with falls. These results suggest the need to incorporate cardiovascular assessments for patients with falls. This review informed the cardiovascular recommendations in the new World Guidelines for falls in older adults.Clinical Trials Registration Number: CRD42021272245.
Topics: Humans; Middle Aged; Aged; Hypotension, Orthostatic; Accidental Falls; Cardiovascular Diseases; Risk Factors; Stroke
PubMed: 37738307
DOI: 10.1093/gerona/glad221 -
Minerva Urology and Nephrology Aug 2023Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and...
BACKGROUND
Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs.
METHODS
Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs.
RESULTS
Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05).
CONCLUSIONS
Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.
Topics: Humans; Doxazosin; Tamsulosin; Hypotension, Orthostatic; Adrenergic alpha-Antagonists; Prazosin; Urogenital Diseases
PubMed: 37067186
DOI: 10.23736/S2724-6051.23.05225-4 -
Neurologic Clinics May 2024Spontaneous intracranial hypotension (SIH) typically presents as an acute orthostatic headache during an upright position, secondary to spinal cerebrospinal fluid leaks.... (Review)
Review
Spontaneous intracranial hypotension (SIH) typically presents as an acute orthostatic headache during an upright position, secondary to spinal cerebrospinal fluid leaks. New evidence indicates that a lumbar puncture may not be essential for diagnosing every patient with SIH. Spinal neuroimaging protocols used for diagnosing and localizing spinal cerebrospinal fluid leaks include brain/spinal MRI, computed tomography myelography, digital subtraction myelography, and radionuclide cisternography. Complications of SIH include subdural hematoma, cerebral venous thrombosis, and superficial siderosis. Treatment options encompass conservative management, epidural blood patches, and surgical interventions. The early application of epidural blood patches in all patients with SIH is suggested.
Topics: Humans; Intracranial Hypotension; Cerebrospinal Fluid Leak; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Neuroimaging; Headache
PubMed: 38575260
DOI: 10.1016/j.ncl.2024.02.002