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Translational Andrology and Urology Dec 2021Erectile dysfunction (ED) is the second sexual dysfunction affecting men. Penile duplex ultrasound (PDU) with intracavernous injection of a vasoactive agent as...
BACKGROUND
Erectile dysfunction (ED) is the second sexual dysfunction affecting men. Penile duplex ultrasound (PDU) with intracavernous injection of a vasoactive agent as alprostadil or papaverine, may play an important role in differentiating psychogenic from vasculogenic ED (arterial or venooclusive) and may also have an important role in the secondary prevention of cardiovascular events. The aim of this study is to investigate the relationship between the vascular parameters and sexual satisfaction as established by a questionnaire.
METHODS
Prospective, multicenter analysis of all patients who underwent a PDU between September 2018 and April 2021 in four centers, including patients who were >18 years old and underwent a PDU for ED, Peyronie's disease (PD) or other reasons, signed informed consent and completed an adapted version of the Brief Sexual Symptom Checklist (BSSC). All the patients underwent a standard technique, and from a total of 325 patients, 16 were excluded because of low testosterone levels, and 15 due to missing data.
RESULTS
A total of 294 patients were included for the analysis. Significant differences were found between patients with and without ED defined by their score in the Sexual Health Inventory for Men (SHIM) questionnaire in the PSV at 10', adjusted for age (38.07 44.95 cm/s; P=0.016), and in the PSV and the EHS at 10' for sexually satisfied and non-satisfied patients, and a significant correlation with those parameters and the probability of being sexually satisfied (r=0.147, P=0.011; r=0.132, P=0.023; respectively).
CONCLUSIONS
In our clinical practice we used the cut-off of >35 cm/s, that seems to be quite low looking at our results. The 10' measurement may be more sensitive in order to establish a diagnosis. BSSC questionnaire is a simple, easy-to perform tool to screen those patients at risk of developing sexual dysfunctions.
PubMed: 35070813
DOI: 10.21037/tau-21-792 -
Nature Communications Jan 2022Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their...
Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.
Topics: Animals; Animals, Genetically Modified; Blood Glucose; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Class II Phosphatidylinositol 3-Kinases; Diabetes Mellitus, Type 2; Gene Expression Regulation; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Longevity; Methylation; Mice; Papaverine; Repressor Proteins; Signal Transduction; Transcription Factors; Vorinostat
PubMed: 35013237
DOI: 10.1038/s41467-021-27732-4 -
Journal of Cardiothoracic Surgery Dec 2021Internal thoracic arteries (ITAs) are the gold standard conduits for coronary revascularization because of their long-term patency and anti-atherosclerotic properties.... (Review)
Review
Internal thoracic arteries (ITAs) are the gold standard conduits for coronary revascularization because of their long-term patency and anti-atherosclerotic properties. Harvesting and preparation of ITAs for revascularization is a technically demanding procedure with multiple challenges. Over the last few decades, various methods and techniques for ITAs harvesting have been introduced by different surgeons and applied in clinical practice with different results. Harvesting of ITAs in pedicled or skeletonized fashion, with electrocautery or harmonic scalpel, with open or intact pleura, with clipping the end or keeping it perfused; papaverine delivery with intraluminal injection, perivascular injection, injecting into endothoracic fascia, and papaverine topical spray are the different techniques introduced by the number of researchers. At the same time, access to the ITAs for harvesting has also been studied. Access and harvesting through median sternotomy, mini anterolateral thoracotomy, thoracoscopic, and robotic-assisted harvesting of ITAs are the different techniques used in clinical practice. However, the single standard method for harvesting and preparation of ITAs has yet to be determined. In this review article, we aimed to discuss and analyze all these techniques of harvesting and preparing ITAs with the help of literature to find the best way for ITAs harvesting and preparation for myocardial revascularization.
Topics: Humans; Mammary Arteries; Myocardial Revascularization; Papaverine; Thoracotomy; Tissue and Organ Harvesting
PubMed: 34961523
DOI: 10.1186/s13019-021-01733-2 -
Frontiers in Bioengineering and... 2021The use of autologous tissue grafts for tunica albuginea repair in Peyronie's disease and congenital chordee is often restricted by limited tissue availability and donor...
The use of autologous tissue grafts for tunica albuginea repair in Peyronie's disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, = 3), or subjected to corporoplasty with BLSF grafts ( = 5); decellularized small intestinal submucosa (SIS) matrices ( = 5); or autologous tunica vaginalis (TV) flaps ( = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.
PubMed: 34950646
DOI: 10.3389/fbioe.2021.791119 -
Molecules (Basel, Switzerland) Oct 2021Papaverine (PPV) is an alkaloid isolated from the . Research has shown that PPV inhibits proliferation. However, several questions remain regarding the effects of PPV in...
Papaverine (PPV) is an alkaloid isolated from the . Research has shown that PPV inhibits proliferation. However, several questions remain regarding the effects of PPV in tumorigenic cells. In this study, the influence of PPV was investigated on the proliferation (spectrophotometry), morphology (light microscopy), oxidative stress (fluorescent microscopy), and cell cycle progression (flow cytometry) in MDA-MB-231, A549, and DU145 cell lines. Exposure to 150 μM PPV resulted in time- and dose-dependent antiproliferative activity with reduced cell growth to 56%, 53%, and 64% in the MDA-MB-231, A549, and DU145 cell lines, respectively. Light microscopy revealed that PPV exposure increased cellular protrusions in MDA-MB-231 and A549 cells to 34% and 23%. Hydrogen peroxide production increased to 1.04-, 1.02-, and 1.44-fold in PPV-treated MDA-MB-231, A549, and DU145 cells, respectively, compared to cells propagated in growth medium. Furthermore, exposure to PPV resulted in an increase of cells in the sub-G phase by 46% and endoreduplication by 10% compared to cells propagated in growth medium that presented with 2.8% cells in the sub-G phase and less than 1% in endoreduplication. The results of this study contribute to understanding of effects of PPV on cancer cell lines.
Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Humans; Oxidative Stress; Papaverine; Reactive Oxygen Species
PubMed: 34770797
DOI: 10.3390/molecules26216388 -
Current Therapeutic Research, Clinical... 2021The extravasation of potassium chloride will cause serious harm, especially if it is not diagnosed or treated promptly. Objective:to report the clinical course of a...
BACKGROUND
The extravasation of potassium chloride will cause serious harm, especially if it is not diagnosed or treated promptly. Objective:to report the clinical course of a patient who was suffering a potassium extravasation and to discuss steps that can be done to decrease the chances of this event from occurring in other patients.
METHODS
After discontinuation of infusion device and withdrawal of intravenous catheter, wet packing with magnesium sulfate and local injection of papaverine and lidocaine were applied.
RESULTS
After 11 days, the extravasation injury had recovered.
CONCLUSIONS
To avoid a repeat of such an adverse event, proper sites for administering, accurate dilution of potassium chloride solutions, close observation, and increased awareness of trained personnel of extravasation dangers are vital. Once extravasation occurs, timely wet application with magnesium sulfate and local injection of papaverine and lidocaine may have been useful in producing a favorable recovery.
PubMed: 34745392
DOI: 10.1016/j.curtheres.2021.100646 -
Experimental Eye Research Nov 2021Increasing the level of cyclic adenosine 3, 5'-monophosphate is an important mechanism for axon outgrowth and recovery of central nervous system function. This study...
Increasing the level of cyclic adenosine 3, 5'-monophosphate is an important mechanism for axon outgrowth and recovery of central nervous system function. This study aimed to investigate the effects of papaverine, a non-specific phosphodiesterase inhibitor, on axon outgrowth of primary retinal ganglion cells from Sprague Dawley rats. Experiments were performed on primary retinal ganglion cells extracted from Sprague Dawley rat pups within 48-72 h of birth. At 24 h after seeding, immunofluorescence was used to identify and calculate the purity of retinal ganglion cells isolated by an improved two-step immunopanning method developed by author Sujia Ma. The effects of a range of papaverine concentrations on axon outgrowth of primary retinal ganglion cells cultures were observed by immunofluorescence and measured by ImageJ software at three different time points: 24, 48, and 72 h. The ability of papaverine to enable retinal ganglion cells to overcome the inhibitory effects of glial scar component chondroitin sulfate proteoglycans was examined using chondroitin sulfate proteoglycans-coated culture plates. Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt, a blocking agent of cyclic adenosine 3, 5'-monophosphate, and dibutyryl cyclic adenosine 3, 5'-monophosphate, an analogue of cyclic adenosine 3, 5'-monophosphate, were used to explore the mechanism of papaverine in promoting retinal ganglion cells axon outgrowth. Our study shows 2 μg/mL papaverine concentration significantly promoted axon outgrowth in primary retinal ganglion cells and restored axon outgrowth of these cells on chondroitin sulfate proteoglycans. Axon outgrowth was blocked by Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt and obviously promoted by dibutyryl cyclic adenosine 3, 5'-monophosphate. Our study is the first to describe the use of papaverine to promote axon outgrowth of retinal ganglion cells. These results may help to expand the application of papaverine, and they provide a cytological basis for papaverine in the treatment of optic nerve injury caused by glaucoma and other diseases.
Topics: Animals; Cells, Cultured; Disease Models, Animal; Glaucoma; Nerve Regeneration; Neuronal Outgrowth; Papaverine; Phosphodiesterase Inhibitors; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells
PubMed: 34687724
DOI: 10.1016/j.exer.2021.108797 -
Diagnosis and Treatment for Pediatric Supracondylar Humerus Fractures with Brachial Artery Injuries.Children (Basel, Switzerland) Oct 2021(1) Background: This study aims to describe the clinical and paraclinical characteristics of and the diagnostic approach to brachial artery injuries in pediatric...
(1) Background: This study aims to describe the clinical and paraclinical characteristics of and the diagnostic approach to brachial artery injuries in pediatric supracondylar humerus fractures, as well as to evaluate intraoperative vascular anatomical lesions and early postoperative results. (2) Methods: A retrospective, hospital-based analysis of medical records at Viet Duc University Hospital (Vietnam), using a sample of children under 16 years who met the diagnostic criteria for supracondylar humerus fractures with brachial artery injuries between January 2016 and December 2020, was performed. A total of 50 patients were included in the analysis. (3) Results: Out of 50 pediatric patients, 36 patients were male (72%) and the mean age was 5.85 years (range, 1.5-14 years). Before treatment, there were 46 patients with severely displaced fractures which were classified as Gartland type III (92%). Following casting, the percentage of those with severely displaced fractures was reduced significantly to 12%, while there were no patients with Gartland type III fractures after percutaneous pinning. Doppler sonography failed to assess vascular lesions at the fracture site before and after casting in most patients. Two-thirds of surgical cases had only vasospasm, without physical damage to the vessel wall or intravascular thrombosis. Preoperative Doppler spectrum analysis was not consistent with the severity of intraoperative brachial artery injury. Out of 24 patients with vasospasm, we performed vascular blockade using papaverin in 11 cases and intraoperative balloon angioplasty of the brachial artery using the Fogarty catheter in 13 cases. Brachial artery graft was performed with 12 patients who had anatomical damage to the vascular wall. A complication of embolism occurred in one patient immediately after surgery, and two patients had superficial infections. One month following surgery, 2 out of 36 patients had a temporary loss of sensation in the area of incision. (4) Conclusions: Most pediatric patients did not present with symptoms of critical limb ischemia similar to those associated with lower extremity vascular injuries. The diagnosis and treatment of pediatric supracondylar humerus fractures with vascular injury is difficult and time-consuming, especially in cases of transverse fractures.
PubMed: 34682198
DOI: 10.3390/children8100933 -
International Journal of Nanomedicine 2021Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia)...
PURPOSE
Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia) in the tumor microenvironment. Herein, we report a therapeutic strategy that greatly enhances the treatment effects of RT.
METHODS
Specifically, papaverine (ppv), an FDA-approved smooth muscle relaxant, was applied in the strategy. Ppv improved blood flow via vasodilation to deliver sufficient oxygen to the hypoxic solid tumor and further resulted in increased tumor penetration of the radiosensitizer, significantly enhancing the radiosensitization compared with no ppv treatment. Additionally, tantalum oxide nanospheres were cloaked in red blood cell membranes (TaOx@M) to achieve greater biocompatibility, non-immunogenicity, and a longer circulation time.
RESULTS
As a high-Z element, tantalum provides localized dose enhancement and thereby boosts the efficacy of RT. Vasodilation, the oxygenation of cancer cells, and the improved accumulation and retention of TaOx@M in the tumor region were verified in vivo. Furthermore, compared with RT alone, the combined vasodilation and nanosphere camouflaging strategy more efficiently suppressed the growth of K7M2 tumors in mice.
CONCLUSION
The results of this study suggest that the integration of TaOx@M and ppv has excellent potential for improving RT efficacy.
Topics: Animals; Cell Line, Tumor; Erythrocytes; Humans; Mice; Neoplasms; Papaverine; Radiation-Sensitizing Agents; Tumor Microenvironment
PubMed: 34675515
DOI: 10.2147/IJN.S324314 -
EuroIntervention : Journal of EuroPCR... Dec 2021Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for...
BACKGROUND
Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for non-invasive imaging.
AIMS
We aimed to elucidate whether serum caffeine is independently associated with adenosine-induced fractional flow reserve (FFR) overestimation and their concentration-response relationship.
METHODS
FFR was measured using adenosine (FFRADN) and papaverine (FFRPAP) in 209 patients. FFRADN overestimation was defined as FFRADN - FFRPAP. The locally weighted scatterplot smoothing (LOWESS) approach was applied to evaluate the relationship between serum caffeine level and FFRADN overestimation. Multiple regression analysis was used to determine independent factors associated with FFRADN overestimation.
RESULTS
Caffeine was ingested at <12 hours in 85 patients, at 12-24 hours in 35 patients, and at >24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (p<0.001). The LOWESS curve demonstrated that FFRADN overestimation started from just above the lower detection limit of serum caffeine and increased approximately 0.01 FFR unit per 1 mg/L increase in serum caffeine level with a linear relationship. The 90th percentile of serum caffeine levels for the ≤12-hour, the 12-24-hour, and the >24-hour groups corresponded to FFRADN overestimations by 0.06, 0.03, and 0.02, respectively.
CONCLUSIONS
Serum caffeine overestimates FFRADN values in a linear concentration-response manner. FFRADN overestimation occurs at much lower serum caffeine levels than those that were previously believed. Our results highlight that standardised caffeine control is required for reliable adenosine-induced FFR measurements.
Topics: Adenosine; Caffeine; Coronary Angiography; Coronary Stenosis; Fractional Flow Reserve, Myocardial; Humans; Hyperemia; Papaverine; Predictive Value of Tests; Vasodilator Agents
PubMed: 34647891
DOI: 10.4244/EIJ-D-21-00453