Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. Methods: A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. Results: 10 studies were included in the review. Intranasal administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration. Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. Conclusion: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow absorption and deposition in the skin. Oral transmucosal administration may potentially be a clinically relevant due to avoiding first-pass metabolism. Subcutaneous injection of melatonin did not document any advantages compared to other administration routes.

Dimethyl sulfoxide (DMSO) has been used for medical Background: treatment and as a pharmacological agent in humans since the 1960s. Today, DMSO is used mostly for cryopreservation of stem cells, treatment of interstitial cystitis, and as a penetrating vehicle for various drugs. Many adverse reactions have been described in relation to the use of DMSO, but to our knowledge, no overview of the existing literature has been made. Our aim was to conduct a systematic review describing the adverse reactions observed in humans in relation to the use of DMSO.This systematic review was reported according to the Methods: PRISMA-harms (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. The primary outcome was any adverse reactions occurring in humans in relation to the use of DMSO. We included all original studies that reported adverse events due to the administration of DMSO, and that had a population of five or more.We included a total of 109 studies. Gastrointestinal and skin Results: reactions were the commonest reported adverse reactions to DMSO. Most reactions were transient without need for intervention. A relationship between the dose of DMSO given and the occurrence of adverse reactions was seen.DMSO may cause a variety of adverse reactions that are Conclusions: mostly transient and mild. The dose of DMSO plays an important role in the occurrence of adverse reactions. DMSO seems to be safe to use in small doses.PROSPERO . Registration: CRD42018096117PubMed Abstract | Publisher Full Text 3. Swanson BN: Medical use of dimethyl sulfoxide (DMSO). Rev Clin Basic Pharm. 1985; 5(1-2): 1-33. PubMed Abstract 4. Paul MM: Interval therapy with dimethyl sulfoxide. Ann N Y Acad Sci. 1967; 141(1): 586-98. PubMed Abstract | Publisher Full Text 5. Kulah A, Akar M, Baykut L: Dimethyl sulfoxide in the management of patient with brain swelling and increased intracranial pressure after severe closed head injury. Neurochirurgia (Stuttg). 1990; 33(6): 177-80. PubMed Abstract | Publisher Full Text 6. Rosenbaum EE, Herschler RJ, Jacob SW: Dimethyl Sulfoxide in Musculoskeletal Disorders. JAMA. 1965; 192: 309-13. PubMed Abstract | Publisher Full Text 7. Morris C, de Wreede L, Scholten M, et al.: Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide. Transfusion. 2014; 54(10): 2514-22. PubMed Abstract | Publisher Full Text 8. Peeker R, Haghsheno MA, Holmäng S, et al.: Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. J Urol. 2000; 164(6): 1912-5, discussion 1915-6. PubMed Abstract | Publisher Full Text 9. Amemori S, Iwakiri R, Endo H, et al.: Oral dimethyl sulfoxide for systemic amyloid A amyloidosis complication in chronic inflammatory disease: a retrospective patient chart review. J Gastroenterol. 2006; 41(5): 444-9. PubMed Abstract | Publ...

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Purpose: To investigate the incidence of inguinal hernia following radical prostatectomy we compared the incidence after open retropubic radical prostatectomy with the incidence after the laparoscopic and robot-assisted radical prostatectomies, and using control groups. Materials and Methods: We included all original articles on studies providing data on inguinal hernia incidence in patients treated with radical prostatectomy for localized prostate cancer. PubMedÒ and EMBASEÒ were searched on February 28, 2018. A meta-analysis was done as a weighted and pooled estimate of the incidence of inguinal hernia. The bias risk was assessed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane Collaboration tool for randomized clinical trials. Results: We included 54 studies with a total of 101,687 patients. The estimated incidence of inguinal hernia was 13.7% (95% CI 12.0e15.4) after open retropubic radical prostatectomy, 7.5% (95% CI 5.2e9.8) after laparoscopic radical prostatectomy and 7.9% (95% CI 5.0e10.9) after robot-assisted laparoscopic radical prostatectomy. In studies comparing the incidence of inguinal hernia after open prostatectomy vs no treatment the incidence was significantly higher in the radical prostatectomy group (11.7%, 95% CI 9.2e14.2 vs 3.3%, 95% CI 2.0e4.6). Two of 3 studies showed a significantly higher incidence after laparoscopic and robot-assisted radical prostatectomies compared with a control group. Most studies of intraoperative inguinal hernia prevention techniques demonstrated a significantly lower inguinal hernia incidence in the experimental group. Inguinal hernias that developed after radical prostatectomy were primarily indirect (81.9%, 95% CI 75.3e88.4). Conclusions: We found a high incidence of inguinal hernia following radical prostatectomy and hernias were primarily of the indirect type. The highest incidence of inguinal hernia was noted after open radical prostatectomy, followed by laparoscopic and robot-assisted radical prostatectomies. There was no significant difference between the laparoscopic and robot-assisted groups. The incidence of inguinal hernia was significantly higher after open radical prostatectomy than in control groups with some evidence to support the same finding for the laparoscopic and robot-assisted approaches. Promising results have been reported in studies of intraoperative prophylactic surgical techniques to reduce the postoperative incidence of inguinal hernia.