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Frontiers in Bioscience (Landmark... Oct 2023Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing... (Review)
Review
Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing research is focusing on the neuroprotective effects of microglia and stem cells. By exerting the bystander effect, secreting exosomes and forming biobridges, mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and multilineage-differentiating stress-enduring cells (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, and reduce neuroinflammation. Exosome-based therapy is now being extensively researched due to its many advantageous properties over cell therapy, such as lower immunogenicity, no risk of blood vessel occlusion, and ease of storage and modification. However, although preclinical studies have shown promising therapeutic outcomes, clinical trials have been associated with several translational challenges. This review explores the therapeutic effects of preconditioned microglia as well as various factors secreted in stem cell-derived extracellular vesicles with their mechanisms of action explained. Furthermore, an overview of preclinical and clinical studies is presented, explaining the main challenges of microglia and stem cell therapies, and providing potential solutions. In particular, a highlight is the use of novel stem cell therapy of Muse cells, which bypasses many of the conventional stem cell limitations. The paper concludes with suggestions for directions in future neuroprotective research.
Topics: Humans; Microglia; Ischemic Stroke; Stroke; Alprostadil; Mesenchymal Stem Cells
PubMed: 37919085
DOI: 10.31083/j.fbl2810269 -
Pharmacoepidemiology and Drug Safety Jan 2024To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal...
PURPOSE
To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs).
METHODS
We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients.
RESULTS
From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively).
CONCLUSIONS
PDE5i use shows disproportionate priapism signals which are higher in young patients.
Topics: Male; Humans; Child, Preschool; Child; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Priapism; Erectile Dysfunction; Tadalafil; Drug-Related Side Effects and Adverse Reactions
PubMed: 37909414
DOI: 10.1002/pds.5721 -
NMR in Biomedicine Mar 2024Recently, intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has also been demonstrated as an imaging tool for applications in neurological and...
Recently, intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has also been demonstrated as an imaging tool for applications in neurological and neurovascular diseases. However, the use of single-shot diffusion-weighted echo-planar imaging for IVIM DWI acquisition leads to suboptimal data quality: for instance, geometric distortion and deteriorated image quality at high spatial resolution. Although the recently commercialized multi-shot acquisition methods, such as multiplexed sensitivity encoding (MUSE), can attain high-resolution and high-quality DWI with signal-to-noise ratio (SNR) performance superior to that of the conventional parallel imaging method, the prolonged scan time associated with multi-shot acquisition is impractical for routine IVIM DWI. This study proposes an acquisition and reconstruction framework based on parametric-POCSMUSE to accelerate the four-shot IVIM DWI with 70% reduction of total scan time (13 min 8 s versus 4 min 8 s). First, the four-shot IVIM DWI scan with 17 b values was accelerated by acquiring only one segment per b value except for b values of 0 and 600 s/mm . Second, an IVIM-estimation scheme was integrated into the parametric-POCSMUSE to enable joint reconstruction of multi-b images from under-sampled four-shot IVIM DWI data. In vivo experiments on both healthy subjects and patients show that the proposed framework successfully produced multi-b DW images with significantly higher SNRs and lower reconstruction errors than did the conventional acceleration method based on parallel imaging. In addition, the IVIM quantitative maps estimated from the data produced by the proposed framework showed quality comparable to that of fully sampled MUSE-reconstructed images, suggesting that the proposed framework can enable highly accelerated multi-shot IVIM DWI without sacrificing data quality. In summary, the proposed framework can make multi-shot IVIM DWI feasible in a routine MRI examination, with reasonable scan time and improved geometric fidelity.
Topics: Humans; Alprostadil; Brain; Diffusion Magnetic Resonance Imaging; Head; Magnetic Resonance Imaging; Echo-Planar Imaging; Motion
PubMed: 37871617
DOI: 10.1002/nbm.5063 -
Zhonghua Nan Ke Xue = National Journal... Dec 2022To investigate the application value of RigiScan monitoring in assisting tadalafil medication.
OBJECTIVE
To investigate the application value of RigiScan monitoring in assisting tadalafil medication.
METHODS
This self-control study included 89 ED patients (IIEF-5 < 21) treated in our hospital from August 2019 to July 2020. The patients underwent audiovisual sexual stimulation (AVSS), nocturnal penile tumescence and rigidity (NPTR) test, scoring on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-Item Scale (GAD-7), blood routine test, blood biochemical analysis, and hormone secretion examination, which confirmed 21 cases of psychogenic, 28 cases of organic and 40 cases of mixed ED. We treated the patients with tadalafil at 5 mg/d for 30 days, followed by examination of their erectile function by IIEF-5 scoring and AVSS and comparison of their erectile function with the baseline. For some of the patients that responded poorly to tadalafil at 5 mg/d, we increased the dose to 20 mg and detected the efficacy by AVSS at 1 h after medication. For those with organic or mixed ED irreponsive to tadalafil at 20 mg, we performed screening for corpora cavernosal venous leakage (CCVL) by intracavernosal injectionof alprostadil and penile color Doppler duplex ultrasonography or used dynamic infusion cavernosometry and cavernosography (DICC) to confirm the diagnosis of CCVL.
RESULTS
The effectiveness rates of 5 mg/d tadalafil on mild, moderate and severe ED were 85.4%, 53.1% and 43.8%, respectively, significantly higher on mild than on moderate and severe ED (P = 0.002), and its effectiveness rates on psychogenic, organic and mixed ED were 90.5%, 60.7% and 57.5%, respectively, remarkably higher on psychogenic than on organic and mixed ED (P = 0.026). For those with organic or mixed ED irresponsive to 5 mg/d tadalafil, the increased dose of 20 mg achieved an effectiveness rate of 64.3%. (P = 0.033). The results of DICC did not encourage tadalafil medication for the cases of organic or mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil.
CONCLUSION
RigiScan monitoring plays a guiding role in tadalafil medication of ED and helps distinguish organic from psychogenic ED. Tadalafil at 5 mg/d produces a better effect on mild than on moderate and severe ED, and so does it on psychogenic than on organic and mixed ED. The dose of medication can be increased to 20 mg for organic and mixed ED irresponsive to 5 mg tadalafil, but tadalafil is not recommended for organic and mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil.
Topics: Male; Humans; Erectile Dysfunction; Tadalafil; Penis; Penile Erection; Ultrasonography, Doppler, Color
PubMed: 37846629
DOI: No ID Found -
International Journal of Molecular... Sep 2023Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the...
Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
Topics: Rats; Humans; Animals; Alprostadil; Diphtheria Toxin; Spinal Cord Injuries; Cell Differentiation; Spinal Cord; Administration, Intravenous
PubMed: 37834052
DOI: 10.3390/ijms241914603 -
Medicine Oct 2023It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous...
BACKGROUND
It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis.
METHODS
We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency.
RESULTS
After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered.
CONCLUSION
For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.
Topics: Male; Humans; Child; Adolescent; Femoral Vein; Anticoagulants; Thrombosis; Blood Coagulation Disorders; Leukemia, Myeloid, Acute; Vitamin K Deficiency; Arteries
PubMed: 37832057
DOI: 10.1097/MD.0000000000035121 -
Expert Review of Gastroenterology &... 2023Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving... (Review)
Review
INTRODUCTION
Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving management, possibly due to their complexity, and studies suggest that a simple setup of concise and behaviorally-orientated steps improves usability.
AREAS COVERED
This article introduces the concept of opioid-induced constipation and provides an overview of existing guidelines in this field. We also propose simplified recommendations for managing opioid-induced constipation, derived from a synthesis of current guidelines and the principles of optimal guideline design theory.
EXPERT OPINION
Despite standard treatment with laxatives and fluid intake in patients with opioid-induced constipation, escalation of treatment is often needed where μ-opioid receptor antagonists or newer medications such as lubiprostone, linaclotide, or prucalopride are used. Previous guidelines have not been used sufficiently and thus management of the condition is often insufficient. We therefore propose simplified recommendations to management, which we believe can come into broader use. It was validated in primary care for credibility, clarity, relevance, usability, and overall benefit. We believe that this initiative can lead to better management of the substantial proportion of patients suffering from side effects of opioids.
Topics: Humans; Constipation; Analgesics, Opioid; Opioid-Induced Constipation; Laxatives; Lubiprostone
PubMed: 37822210
DOI: 10.1080/17474124.2023.2267441 -
Japanese Journal of Radiology Mar 2024To compare multiplexed sensitivity-encoding diffusion-weighted magnetic resonance imaging (MUSE-DWI) and conventional DWI (cDWI) techniques in thyroid MRI.
PURPOSE
To compare multiplexed sensitivity-encoding diffusion-weighted magnetic resonance imaging (MUSE-DWI) and conventional DWI (cDWI) techniques in thyroid MRI.
MATERIALS AND METHODS
Nineteen patients who underwent thyroid MRI using both MUSE-DWI and cDWI at a 3.0 T MRI system were enrolled. Qualitative parameters (image quality, thyroid contour, and lesion conspicuity) and quantitative parameters (signal-to-noise ratio (SNR), lesion-to-thyroid contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC)) were compared between the two sequences. In addition, ADC values derived from MUSE-DWI and cDWI were separately compared between benign and malignant lesions.
RESULTS
MUSE-DWI outperformed cDWI in terms of image quality, thyroid contour, and lesion conspicuity. Significantly, higher signal-to-noise ratio (SNR) in both the thyroid and its lesion were found in MUSE-DWI than those in cDWI (both P < 0.05). The lesion-to-thyroid contrast-to-noise ratio (CNR) values were also significantly higher in MUSE-DWI than those in cDWI (P < 0.05). The apparent diffusion coefficient (ADC) of the thyroid in MUSE-DWI was significantly lower than that in cDWI (P < 0.05). The ADC of the lesion in MUSE-DWI was also significantly lower than that in cDWI (P < 0.05). In addition, ADC values derived from MUSE-DWI and cDWI were significantly higher in benign lesions than malignant lesions (P < 0.05).
CONCLUSION
Compared with cDWI, MUSE-DWI can improve the image quality, thyroid contour sharpness, lesion conspicuity, SNR in both the thyroid and its lesions, and enhancing the CNR between lesions and thyroid.
Topics: Humans; Alprostadil; Thyroid Gland; Echo-Planar Imaging; Signal-To-Noise Ratio; Diffusion Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 37819591
DOI: 10.1007/s11604-023-01500-4 -
European Journal of Obstetrics,... Dec 2023To compare cesarean rates and maternal and neonatal morbidity according to the cervical ripening method used among obese pregnant women requiring induction of labor at...
Comparison of cesarean delivery rates after 3 methods of cervical ripening among obese women at or after 41 weeks - Secondary analysis of two French randomized controlled trials: MAGPOP and CYTOPRO.
OBJECTIVE
To compare cesarean rates and maternal and neonatal morbidity according to the cervical ripening method used among obese pregnant women requiring induction of labor at or after 41 weeks of gestation.
DESIGN
A secondary analysis of two multicenter randomized controlled trials conducted in French maternity units between 2015 and 2018.
PARTICIPANTS
336 women with a body mass index ≥30 kg/m, a pregnancy ≥41 weeks, and an induction of labor requiring cervical ripening.
INTERVENTIONS
Cervical ripening with a PGE2 dinoprostone pessary (Propess®), or low-dose vaginal PGE1 (misoprostol) or a double-balloon catheter.
MEASUREMENTS AND FINDINGS
The rates of cesarean delivery did not differ significantly according to the cervical ripening method (PGE2 pessary vs PGE1, RR: 1.18, 95% CI: 0.80-1.75; PGE2 pessary vs double balloon catheter: RR, 0.88, 95% CI: 0.60-1.29), p = 0.52; double balloon catheter vs PGE1, RR: 1.34, 95% CI: 0.77-2.32, p = 0.29). More oxytocin was required for women from the double-balloon group compared to those from both the PGE1 and PGE2 pessary groups (respectively, RR: 1.31, 95% CI: 1.08-1.58, p = 0.005; RR: 1.17, 95% CI: 1.03-1.32, p = 0.01). The risk of perineal tears or episiotomy was significantly lower for women induced with the PGE2 pessary than with PGE1 (0.85; 95% CI: 0.74-0.99), p = 0.03).
KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE
No cervical ripening method was associated with a lower cesarean rate in obese women who required cervical ripening from 41 weeks. Further trials are required among obese women to determine the cervical ripening method most efficacious for reducing the cesarean rate.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Dinoprostone; Oxytocics; Alprostadil; Labor, Induced; Cervical Ripening; Randomized Controlled Trials as Topic; Obesity
PubMed: 37806026
DOI: 10.1016/j.ejogrb.2023.09.019 -
Sexual Medicine Reviews Sep 2023Erectile dysfunction (ED) is the inability to achieve or maintain erection for satisfactory sexual performance. ED drastically reduces the quality of life for men and... (Review)
Review
INTRODUCTION
Erectile dysfunction (ED) is the inability to achieve or maintain erection for satisfactory sexual performance. ED drastically reduces the quality of life for men and their partners and is commonly linked to comorbid conditions such as diabetes and cardiovascular disease. As a result, clinicians and researchers are working to improve treatments for ED. Current guideline-approved ED treatments include oral phosphodiesterase type 5 inhibitors, intraurethral alprostadil, penile intracavernosal injections, and penile prosthesis surgery. Today, there is increasing interest in restorative therapies such as intracavernosal platelet-rich plasma (PRP) for the management of ED.
OBJECTIVES
This narrative review describes the current trials investigating intracavernosal PRP for ED and proposes future directions to increase the strength of evidence to support use of PRP in this population.
METHODS
A comprehensive literature search of PubMed, Science Direct, and Scopus was performed to identify all randomized clinical trials using PRP for the treatment of ED.
RESULTS
We identified 4 randomized clinical trials investigating the safety and efficacy of PRP for ED. We found significant heterogeneity among study protocols, including collection of PRP, dosing of PRP, and follow-up.
CONCLUSION
While intracavernosal PRP is considered safe, its efficacy for the management of ED remains unknown due to variability among clinical trials.
Topics: Male; Humans; Erectile Dysfunction; Quality of Life; Penile Erection; Phosphodiesterase 5 Inhibitors; Platelet-Rich Plasma
PubMed: 37786350
DOI: 10.1093/sxmrev/qead032