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Med. Sci., Volume 7, Issue 9 (September 2019) – 9 articles

Cover Story (view full-size image): Kappa-opioid agonists (KOAs) enhance cardiac performance and reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis; however, there has been limited development of KOAs as a class due to the promotion of untoward central nervous system (CNS)-mediated side effects. The Dix lab has developed a peripherally-restricted, orally-active, KOA (JT09) for the treatment of pain and cardiovascular disease. Peripherally-restricted KOAs have a limited side-effect profile and demonstrate potential in preventing heart failure. In this study, we establish a preliminary diuretic profile for lead compound JT09 following single oral administration to adult male Sprague Dawley rats. View this paper.
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16 pages, 287 KiB  
Review
Medical Management of Peyronie’s Disease: Review of the Clinical Evidence
by Patrick Teloken and Darren Katz
Med. Sci. 2019, 7(9), 96; https://doi.org/10.3390/medsci7090096 - 18 Sep 2019
Cited by 6 | Viewed by 5849
Abstract
Peyronie’s disease is a condition that causes abnormal healing of the tunica albuginea, causing penile curvature. It is difficult to treat and its management is continuing to evolve. Proposed non-surgical treatments have included oral, topical, intralesional, extracorporeal shockwave, and traction therapy. The study [...] Read more.
Peyronie’s disease is a condition that causes abnormal healing of the tunica albuginea, causing penile curvature. It is difficult to treat and its management is continuing to evolve. Proposed non-surgical treatments have included oral, topical, intralesional, extracorporeal shockwave, and traction therapy. The study of Peyronie’s disease is made difficult by heterogeneity in the timing of presentation, severity and characteristics of deformity, and associated complaints. Moreover, meta-analyses of studies are difficult due to inconsistencies across study endpoints and the duration of treatments. This article reviews the current clinical evidence and guideline recommendations, with a focus on an improvement in penile curvature. Full article
(This article belongs to the Special Issue Men's Sexual Health)
10 pages, 201 KiB  
Review
A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome
by Michael Costello, Rhonda Garad, Roger Hart, Hayden Homer, Louise Johnson, Cailin Jordan, Edgar Mocanu, Jie Qiao, Luk Rombauts, Helena J. Teede, Eszter Vanky, Christos Venetis and William Ledger
Med. Sci. 2019, 7(9), 95; https://doi.org/10.3390/medsci7090095 - 10 Sep 2019
Cited by 26 | Viewed by 6061
Abstract
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
9 pages, 649 KiB  
Article
Serum Interleukin-8 in Patients with Different Origin of Intra-Abdominal Infections in Perioperative Period
by Artem Riga, Valeriy Boyko and Yuriy Grirorov
Med. Sci. 2019, 7(9), 94; https://doi.org/10.3390/medsci7090094 - 8 Sep 2019
Cited by 1 | Viewed by 2146
Abstract
Intra-abdominal infections (IAI) are associated with high levels of pro-inflammatory serum IL-8 and poor outcomes, but data on IL-8 levels in various inflammatory reactions are contradictory. A better understanding of the diagnostic role of IL-8 is important, since the clinical relevance remains unclear. [...] Read more.
Intra-abdominal infections (IAI) are associated with high levels of pro-inflammatory serum IL-8 and poor outcomes, but data on IL-8 levels in various inflammatory reactions are contradictory. A better understanding of the diagnostic role of IL-8 is important, since the clinical relevance remains unclear. Methods: That was a single-center observational longitudinal cross-sectional study included 56 patients with various origins of intra-abdominal infections: 24 patients with postoperative abscesses, 12 patients with primary intra-abdominal abscesses, and 20 patients with diffuse peritoneal collection. Perioperative serum concentrations of interleukin-8 IL-8 were investigated at the day before surgery, on the 2nd–3rd day, and on the 5th–7th day after surgery. The hypothesis suggested that there was a difference in serum IL-8 in patients with IAI of different origin in the perioperative period. Results: The study showed that the level of serum IL-8 in patients with intra-abdominal infections of different origins is lower in comparison with healthy individuals. Despite the fact that we did not detect any statistically significant differences in the level of IL-8 in serum in IAI of different origin in the perioperative period, its lowest index was observed in the patients with postoperative abscesses on the 5th–7th days after surgical intervention. The levels of serum IL-8 ≤49.71 pg/mL and ≤48.88 pg/mL may serve as diagnostic markers for primary and postoperative abscesses with significant sensitivity and specificity. Conclusions: Our results differ from previous studies that showed high serum IL-8. High-quality clinical trials are needed to better comprehend the role of inflammatory mediators in IAI with different origin. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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12 pages, 1853 KiB  
Article
Diuretic Activity of a Novel Peripherally-Restricted Orally-Active Kappa Opioid Receptor Agonist
by Tyler C. Beck, Matthew A. Hapstack, Gautam S. Ghatnekar and Thomas A. Dix
Med. Sci. 2019, 7(9), 93; https://doi.org/10.3390/medsci7090093 - 31 Aug 2019
Cited by 3 | Viewed by 2575
Abstract
Kappa-opioid agonists (KOAs) enhance cardiac performance, as well as reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis; however, there has been limited development of KOAs as a class due to the promotion of untoward central [...] Read more.
Kappa-opioid agonists (KOAs) enhance cardiac performance, as well as reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis; however, there has been limited development of KOAs as a class due to the promotion of untoward central nervous system (CNS)-mediated side effects. Our laboratory has developed a peripherally-restricted, orally-active, KOA (JT09) for the treatment of pain and cardiovascular disease. Peripherally-restricted KOAs possess a limited side-effect profile and demonstrate potential in preventing heart failure. The aim of this study was to assess the diuretic activity of lead compound JT09 relative to vehicle control and Tolvaptan through single oral administration to adult male Sprague–Dawley rats. JT09-administered rats demonstrated significantly increased urine output relative to vehicle control. However, the effect persisted for 8 h, whereas Tolvaptan-administered rats demonstrated diuretic activity for 24 h. Relative to Tolvaptan, urine output was significantly reduced in JT09 administered animals at all-time points, suggesting that the overall diuretic effect of JT09 is less profound than Tolvaptan. Additionally, JT09-administered rats demonstrated alterations in clinical chemistry; reduced urine specific gravity; and increased urine pH relative to vehicle control. The following study establishes a preliminary diuretic profile for JT09. Full article
(This article belongs to the Section Cardiovascular Disease)
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9 pages, 230 KiB  
Perspective
Incidence and Prevalence of Polymyalgia Rheumatica (PMR): The Importance of the Epidemiological Context. The Italian Case
by Ciro Manzo
Med. Sci. 2019, 7(9), 92; https://doi.org/10.3390/medsci7090092 - 30 Aug 2019
Cited by 18 | Viewed by 3339
Abstract
Objectives: to evaluate incidence and prevalence rates of polymyalgia rheumatica (PMR) in Italy, depending on the epidemiological methodology used from time to time. Materials and Methods: A comprehensive literature search in MEDLINE and EMBASE was carried out. The following search terms were used: [...] Read more.
Objectives: to evaluate incidence and prevalence rates of polymyalgia rheumatica (PMR) in Italy, depending on the epidemiological methodology used from time to time. Materials and Methods: A comprehensive literature search in MEDLINE and EMBASE was carried out. The following search terms were used: polymyalgia rheumatica, incidence, prevalence, epidemiology, general practitioner, family medicine, Italy. A search was also carried out in Google scholar using the search phrase: epidemiology of polymyalgia rheumatica in Italy. The period considered was between 1970 and March 2019. All articles containing data on incidence and prevalence of PMR in Italy were read in full. Reviews and non-original manuscripts were excluded as well as all the studies containing incidence and prevalence rates of giant cell arteritis (GCA), unless clearly distinct from data related to patients with PMR alone (isolated and pure PMR). Results: Five articles corresponded to inclusion and exclusion criteria. Two articles were excluded as they were review articles, and three articles were excluded because there were not clear data on incidence and prevalence rates of isolated PMR. Three articles reported data on the annual incidence of PMR (two of them published by the same group of investigators); two articles reported prevalence data. In one article, both incidence and prevalence were calculated. The annual rate of incidence of PMR was between 0.12 and 2.3 cases/1000 inhabitants aged over 50 years. In the two studies publishing prevalence data, they varied from 0.37% to 0.62%. The differences in incidence and prevalence rates were related to several factors such as the different set of diagnostic criteria used for identifying patients or the diagnostic difficulty for patients with atypical presentations, specifically those without raised erythrocyte sedimentation rate (ESR). In the study with higher annual rate of incidence and higher prevalence of PMR, the collaboration between general practitioner (GP) and the out-of-hospital public rheumatologist resulted in significantly different data than in the other studies. All the five articles presented data from monocentric cohorts. Conclusion: Very few Italian studies addressed the epidemiology of PMR. The contribution of a specific professional figure represented by the out-of-hospital public rheumatologist, present in the Italian National Health System and absent in other countries, can make the Italian experience unique in its kind. Full article
11 pages, 268 KiB  
Review
A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction
by Eric Chung
Med. Sci. 2019, 7(9), 91; https://doi.org/10.3390/medsci7090091 - 29 Aug 2019
Cited by 15 | Viewed by 9678
Abstract
Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the [...] Read more.
Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the current therapeutic options only address the symptoms of ED and not the underlying pathogenesis that results in ED. Newer and novel ED therapies aspire to reverse ED conditions by preventing cavernosal fibrosis, promoting endothelial revascularization and modulating various neuro-hormonal pathways. Regenerative therapeutic strategies such as low-intensity shock wave, gene and cellular-based therapies, and penile transplants are designed to improve penile hemodynamics and revitalize the cavernosal smooth muscle to mitigate and/or reverse underlying ED. This state-of-art article evaluates current and emerging therapeutic options for ED. Full article
(This article belongs to the Special Issue Men's Sexual Health)
12 pages, 388 KiB  
Review
Erectile Dysfunction: A Primer for in Office Management
by Samir Sami, Noah Stern, Andrew Di Pierdomenico, Brandon Katz and Gerald Brock
Med. Sci. 2019, 7(9), 90; https://doi.org/10.3390/medsci7090090 - 29 Aug 2019
Cited by 1 | Viewed by 4845
Abstract
Introduction: Optimizing erectile dysfunction (ED) remains a clinically significant endeavor as insufficient outcomes from oral, injectable and even surgical approaches to treatment remain less than ideal. In this report, we integrate evolving knowledge and provide an algorithmic approach for the clinician to fine-tune [...] Read more.
Introduction: Optimizing erectile dysfunction (ED) remains a clinically significant endeavor as insufficient outcomes from oral, injectable and even surgical approaches to treatment remain less than ideal. In this report, we integrate evolving knowledge and provide an algorithmic approach for the clinician to fine-tune management. Methods: We performed a PubMed and Medline search of Erectile Dysfunction treatment optimization, enhanced patient efficacy for ED, and why men fail ED treatment. All relevant papers for the past two decades were reviewed. Results: Establishing the goals and objectives of the patient and partner while providing detailed instructions for treatment can minimize failures and create an environment that allows treatment optimization. A thorough work-up may identify reversible or contributing causes. We identified several areas where treatment of ED could be optimized. These include; management of associated medical conditions, lifestyle improvements, PDE5 inhibitor prescription strategies, management of hypogonadism and the initiation of intracavernosal injection therapy (ICI). Conclusions: In our view, once a man presents for help to the clinician, use of the simple strategies identified in this review to optimize the tolerability, safety and effectiveness of the selected treatment should result in enhanced patient and partner satisfaction, with improved outcomes. Full article
(This article belongs to the Special Issue Men's Sexual Health)
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12 pages, 1246 KiB  
Review
The Mechanism of Androgen Actions in PCOS Etiology
by Valentina Rodriguez Paris and Michael J. Bertoldo
Med. Sci. 2019, 7(9), 89; https://doi.org/10.3390/medsci7090089 - 28 Aug 2019
Cited by 81 | Viewed by 17668
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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6 pages, 949 KiB  
Article
Autologous Blood Patch for Persistent Ascites Leak from Non-Closing Paracentesis Tracts
by Nazia Khan and Kevin M. Dushay
Med. Sci. 2019, 7(9), 88; https://doi.org/10.3390/medsci7090088 - 22 Aug 2019
Cited by 2 | Viewed by 10155
Abstract
Ascites, the fluid accumulation in the peritoneal cavity, is most commonly seen in patients with end-stage liver disease (ESLD). Evaluating ascites or providing symptomatic relief for patients is accomplished by performing a paracentesis. Ascites leak from a paracentesis site can be a complication [...] Read more.
Ascites, the fluid accumulation in the peritoneal cavity, is most commonly seen in patients with end-stage liver disease (ESLD). Evaluating ascites or providing symptomatic relief for patients is accomplished by performing a paracentesis. Ascites leak from a paracentesis site can be a complication of the procedure and is associated with increased morbidity. Currently, the best options for these patients include medical management or surgical abdominal wall layer closure. Utilizing a blood patch provides an alternative approach to managing such patients. A two-center prospective case series was performed evaluating the efficacy of the blood patch in patients with significant persistent ascites leak following a paracentesis. About 30 mL of the patients’ peripheral blood was used for the blood patch. Subjects were recruited over a period of one year and followed for 30 days after the procedure. A total of six patients were recruited for this study. Subjects underwent placement of autologous blood patch at the site of the ascites leak and 100% had resolution of the leak within 24 h. None of the subjects developed any complications of the procedure. This study shows that an autologous blood patch is an effective, low-risk treatment method for ascites leaks following a paracentesis. It is a simple bedside procedure that can reduce morbidity in patients with end-stage liver disease. Full article
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