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Urologia 2015Erectile dysfunction (ED) is a very common disorder with a deep impact on patients and their partners. Several options are now available for treating ED; oral... (Review)
Review
Erectile dysfunction (ED) is a very common disorder with a deep impact on patients and their partners. Several options are now available for treating ED; oral pharmacotherapy with phosphodiesterase-5 (PDE5) inhibitors currently represents the first-line option for many ED patients. Vitaros©/Virirec© is new topical, non-invasive treatment for ED that offers the combination of an active drug (alprostadil, a synthetic PGE1) with a skin enhancer that improves its local absorption directly at the site of action. Vitaros©/Virirec© has a favorable pharmacodynamic profile and is poorly absorbed in systemic circulation. This makes it suitable in any circumstances and results in a reduced risk of adverse events (AEs), being systemic AEs reported in only 3% of the treated population. Its clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 μg dose in patients with severe ED significantly better than placebo. Its fast onset of action together with its favorable toxicity profile and lack of interactions with other drugs makes Vitaros©/Virirec© a first-line therapeutic option for patients with ED, particularly for individuals who are reluctant to take systemic treatments or with AEs. It may also have an important role in patients not responding to PDE5 inhibitors, particularly those with ED after radical prostatectomy.
Topics: Alprostadil; Erectile Dysfunction; Humans; Male; Skin Cream; Treatment Outcome; Vasodilator Agents
PubMed: 25744707
DOI: 10.5301/uro.5000116 -
The New England Journal of Medicine Apr 1996Erectile dysfunction is a common medical problem affecting many men. Although several intracavernosal therapies are available, their efficacy and safety have not been... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Erectile dysfunction is a common medical problem affecting many men. Although several intracavernosal therapies are available, their efficacy and safety have not been studied systematically.
METHODS
We investigated the efficacy and safety of alprostadil formulated for intracavernosal treatment in three separate multi-institutional, prospective studies in men with erectile dysfunction of vasculogenic, neurogenic, psychogenic, and mixed causes. Clinical and laboratory evaluations of erection and the feasibility of satisfactoriness of sexual activity as assessed both by the men and by their partners were the primary measures of efficacy.
RESULTS
In a dose-response study of 296 men, all doses of alprostadil were superior to placebo and there was a significant dose-response relation (P < / = 0.001), resulting in higher response rates with increasing doses of alprostadil (from 2.5 to 20 microg). In a dose-finding study of 201 men, the minimal effective dose was < / = 2 microg in 23, 20, 38 and 23 percent of men with erectile dysfunction of neurogenic, vasculogenic, psychogenic, or mixed causes, respectively. In a six-month self-injection study in 683 men, the participants reported being able to have sexual activity after 94 percent of the injections. The men and their partners rated the sexual activity as satisfactory after 87 and 86 percent of the injections, respectively. Penile pain, usually mild, occurred in 50 percent of the men at some time but after only 11 percent of the injections. Prolonged erections occurred in 5 percent of the men, priapism in 1 percent, penile fibrotic complications in 2 percent, and hematoma or ecchymosis in 8 percent.
CONCLUSIONS
In men with erectile dysfunction, intracavernosal injection of alprostadil is an effective therapy with tolerable side effects.
Topics: Adult; Aged; Alprostadil; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Pain; Penis; Prospective Studies; Self Administration; Treatment Outcome; Vasodilator Agents
PubMed: 8596569
DOI: 10.1056/NEJM199604043341401 -
Journal of Cerebral Blood Flow and... Dec 2023Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing... (Randomized Controlled Trial)
Randomized Controlled Trial
Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).
Topics: Humans; Ischemic Stroke; Alprostadil; Stroke; Double-Blind Method; Treatment Outcome; Brain Ischemia
PubMed: 37756573
DOI: 10.1177/0271678X231202594 -
Asian Journal of Andrology Nov 2006The pathophysiology of diabetes is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction (ED) in diabetic patients... (Review)
Review
The pathophysiology of diabetes is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction (ED) in diabetic patients includes elevated advanced glycation end-products (AGEs) and increased levels of oxygen free radicals, impaired nitric oxide (NO) synthesis, increased endothelin B receptor binding sites and ultrastructural changes, upregulated RhoA/Rho-kinase pathway, NO-dependent selective nitrergic nerve degeneration and impaired cyclic guanosine monophosphate (cGMP)-dependent kinase-1 (PKG-1). The treatment of diabetic ED is multimodal. Treatment of the underlying hyperglycemia and comorbidities is of utmost importance to prevent or halt the progression of the disease. The peripherally acting oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of oral medical treatment of ED in diabetics. Vacuum erection devices are an additional treatment as a non-invasive treatment option. Local administration of vasoactive medication via urethral suppository or intracorporal injection can be effective with minimal side-effects. Patients with irreversible damage of the erectile mechanism are candidates for penile implantation. Future strategies in the evolution of the treatment of ED are aimed at correcting or treating the underlying mechanisms of ED. With an appropriate vector, researchers have been able to transfect diabetic animals with agents such as neurotrophic factors and nitric oxide synthase (NOS). Further studies in gene therapy are needed to fully ascertain its safety and utility in humans.
Topics: Alprostadil; Cyclic GMP-Dependent Protein Kinases; Diabetes Complications; Diabetic Neuropathies; Erectile Dysfunction; Glycation End Products, Advanced; Humans; Male; Nitric Oxide; Penile Erection; Penile Prosthesis; Penis; Phosphodiesterase Inhibitors; Receptor, Endothelin B; Suppositories; Vacuum
PubMed: 16892168
DOI: 10.1111/j.1745-7262.2006.00223.x -
Digestive Diseases and Sciences Mar 1988Neonatal necrotizing enterocolitis is the most common serious gastrointestinal disorder encountered in neonatal intensive care units. It is a major cause of morbidity... (Review)
Review
Neonatal necrotizing enterocolitis is the most common serious gastrointestinal disorder encountered in neonatal intensive care units. It is a major cause of morbidity and mortality in the newborn, particularly in premature infants. Consistent risk factors are birth weight and prematurity. Polycythemia and hyperviscosity altering blood flow and infectious agents are also implicated. Clinical findings include abdominal distention and diarrhea, and systemic symptoms such as apnea, acidosis, and lethargy. Pneumatosis intestinalis can be demonstrated radiographically. Mucosal ulcerations, hemorrhage, and thrombosis occur early, followed by inflammatory changes. Later still necrosis develops. Ischemia, infection, and enteral feedings are suspected to be involved in the pathophysiology. Eicosanoids, especially thromboxane, platelet-activating factor, and leukotrienes are likely mediators.
Topics: Alprostadil; Arachidonic Acid; Arachidonic Acids; Enterocolitis, Pseudomembranous; Humans; Infant, Newborn; Intestines; Ischemia; Risk Factors; Thromboxanes
PubMed: 3126029
DOI: 10.1007/BF01538135 -
AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation.Nature Communications Feb 2024Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical...
Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAV) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (P). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAV enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAV to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAV-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.
Topics: Mice; Humans; Animals; Alprostadil; Transgenes; Cycloparaffins; Odorants; Receptors, G-Protein-Coupled; Dependovirus; Genetic Vectors
PubMed: 38321056
DOI: 10.1038/s41467-024-45383-z -
Canadian Journal of Gastroenterology =... Oct 2011The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic... (Review)
Review
The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.
Topics: Alprostadil; Bile Acids and Salts; Chloride Channels; Chronic Disease; Constipation; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Organic Anion Transporters, Sodium-Dependent; Peptides; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists; Serotonin Agents; Symporters
PubMed: 22114755
DOI: No ID Found -
Esophagus : Official Journal of the... Jul 2023To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease...
BACKGROUND
To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD).
METHODS
A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital (Shanghai, China)from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects.
RESULTS
Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference.
CONCLUSION
TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn.
TRIAL REGISTRATION
ChiCTR2000034350.
Topics: Humans; Fundoplication; Alprostadil; Quality of Life; Proton Pump Inhibitors; Ultrasonics; Treatment Outcome; China; Gastroesophageal Reflux
PubMed: 36877412
DOI: 10.1007/s10388-023-00992-3 -
Family Planning Perspectives 1995A review of 12 published studies on patient attitudes and reactions to early first-trimester pregnancy termination by medical methods shows consistent patterns, despite... (Review)
Review
A review of 12 published studies on patient attitudes and reactions to early first-trimester pregnancy termination by medical methods shows consistent patterns, despite important differences in study design, measurement and outcome. In most trials that offered participants a choice between surgical and medical abortion, 60-70% of patients chose the medical method. The most common reasons cited for choosing the medical method were greater privacy and autonomy, less invasiveness and greater naturalness than surgery. Frequently mentioned drawbacks included pain, the duration of bleeding, the number of visits, and the waiting time to know if the treatment has been successful. Most women who had a medical abortion said they were satisfied with the method, would recommend it to friends and would use it again if they needed another abortion.
Topics: Abortifacient Agents; Abortion, Induced; Alprostadil; Attitude of Health Personnel; Clinical Trials as Topic; Female; Humans; Mifepristone; Patient Acceptance of Health Care; Pregnancy; Pregnancy Trimester, First; Prostaglandins, Synthetic
PubMed: 7589354
DOI: No ID Found -
Proceedings of the National Academy of... Apr 2004This article describes three distinct strategies by which stereochemically complex molecules are synthesized and the ways asymmetric catalysis can impact on all three.... (Review)
Review
This article describes three distinct strategies by which stereochemically complex molecules are synthesized and the ways asymmetric catalysis can impact on all three. The development of general methods to prepare synthetically useful building blocks leads to an expanded "chiral pool" of potential starting materials for asymmetric synthesis. The possibility of discovering new reactions to access new types of building blocks is particularly attractive and serves to help define the frontiers of the field. Asymmetric catalysis can also be applied to diastereoselective synthesis such that the stereochemistry of the catalyst, and not that of the substrate, determines the relative configuration of the product. Finally, in reactions where multiple stereocenters are generated simultaneously or in tandem, catalyst and substrate control can operate in a complementary manner to achieve one of many possible stereochemical outcomes selectively.
Topics: Alkaloids; Alkenes; Alprostadil; Catalysis; Chemistry, Organic; Furans; Hexoses; Lactones; Organic Chemicals; Oxazoles; Polyenes; Pyrans; Pyrones; Spiro Compounds; Stereoisomerism
PubMed: 15020767
DOI: 10.1073/pnas.0307893101