In-silico and in-vivo evaluation of sesamol and its derivatives for benign prostatic hypertrophy.
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ABSTRACT: Supplementary information
The online version contains supplementary material available at 10.1007/s13205-021-02952-z.
SUBMITTER: Shah A
PROVIDER: S-EPMC8364611 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Benign prostatic hyperplasia (BPH)is the most common condition in aging men, associated with lower urinary tract symptoms. It is caused due to the augmented levels of the androgen dihydrotestosterone. Dutasteride, a 5?-Reductase inhibitor has been recommended for the treatment of BPH upon oral administration. However, long term oral administration of dutasteride may cause sexual problem in man. Therefore the main objective of this study was to develop transdermal patch having nanoemulsion gel of dutasteride in order to enhance physical and chemical stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was prepared by aqueous phase-titration method and characterized by droplet size, viscosity and refractive index. In-vitro skin permeation of dutasteride through rat abdominal skin was determined by the Franz diffusion cell.Significant increase in the steady state flux (J ss), permeability coefficient (K p) and enhancement ratio (E r) was observed in optimized nanoemulsion formulation A1 (p < 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with respect to control which indicates transdermal delivery may be better approach for BPH. Stability studies were performed for the period of 3 months. It was found that droplet size, viscosity and refractive index were slightly increased at refrigerator and room temperature in 3 months period. However, the changes in these parameters were not statistically significant (p ? 0.05). The shelf-life of optimized nanoemulsion A1 was found to be 2.18 years at room temperature. These results indicated that both physical as well as chemical stability of dutasteride in nanoemulsion formulation.
| S-EPMC4232777 | biostudies-literature
Project description:PurposeThis study aimed to assess the clinical outcomes of prostatic urethral lift in Korean patients with bothersome lower urinary tract symptoms due to benign prostatic hyperplasia (BPH).Materials and methodsThirty-two men with symptomatic BPH were consecutively treated in a tertiary care center in Korea. To be included in the present analysis, patients had to meet the following criteria: age ≥50 years, International Prostatic Symptom Score (IPSS) >12, and prostate volume between 30 mL and 80 mL. Patients were evaluated up to a median follow-up period of 1 year post-procedure. The primary outcomes included symptom relief, improvement of quality of life (QOL), and preservation of sexual function.ResultsAll procedures were finished with a mean of 2.2 implants without any serious complication. The numbers of patients diagnosed with diabetes mellitus, hypertension, and ischemic heart disease were 16 (50.0%), 24 (75.0%), and 9 (28.1%), respectively. Patients experienced symptom relief by 1 week that was sustained for 12 months. The mean IPSS, QOL, and maximum flow rate improved to 43%, 70%, and 25% by 1 week, and to 41%, 60%, and 32% by 12 months (p<0.001), respectively. There were no occurrences of early urge incontinence, retrograde ejaculation, or erectile dysfunction. Patient-reported adverse events were mild and transient.ConclusionsProstatic urethral lift is a safe and effective treatment for BPH in the Asian population. This treatment is minimally invasive, can be performed under local anesthesia, and may be an appropriate method for fragile patients.
| S-EPMC7308227 | biostudies-literature
Project description:The prevalence of benign prostatic hypertrophy (BPH) causing bothersome lower urinary tract symptoms increases with our ageing population. Treatment of BPH traditionally begins with medical therapy and surgical intervention is then considered for those whose symptoms progress despite treatment. Minimally invasive surgical therapies have been developed as an intermediary in the treatment of BPH with the aim of decreasing the invasiveness of interventions. These therapies also aim to reduce morbidity and dysfunction related to invasive surgical procedures. Multiple treatment options exist in this group including mechanical and thermo-ablative strategies. Emerging therapies utilizing differing technologies range from the established to the experimental. We review the current literature related to these minimally invasive therapies and the evidence of their effectiveness in treating BPH. The role of minimally invasive surgical therapies in the treatment of BPH is still yet to be strongly defined. Given the experimental nature of many of the modalities, further study is required prior to their recommendation as alternatives to invasive surgical therapy. More mature evidence is required for the analysis of durability of effect of these therapies to make robust conclusions of their effectiveness.
| S-EPMC5448728 | biostudies-other
Project description:Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson's and Alzheimer's disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives. They were constructed by adding four functional groups (-OH, -NH2, -COOH, and -SH) in three different positions of the sesamol molecular framework. A total of 50 derivatives between mono-, di-, and trisubstituted compounds were obtained. All the derivatives were evaluated and compared with a reference set of commercial neuroprotective drugs. The estimated properties are absorption, distribution, metabolism, excretion, toxicity, and synthetic accessibility. Selection and elimination scores were used to choose a first set of promising candidates. Acid-based properties and reactivity indexes were then estimated using the density functional theory. Four sesamol derivatives were finally selected, which are hypothesized to be potent antioxidants, even better than sesamol and Trolox for that purpose.
| S-EPMC7191856 | biostudies-literature
Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.
| S-EPMC7485377 | biostudies-literature
Project description:BackgroundBenign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and significant morbidity in the majority of older men. Plasma markers of oxidative stress are increased in men with BPH but it is unclear whether oxidative stress and/or oxidative DNA damage are causal in the pathogenesis of BPH.MethodsLevels of 8-OH deoxyguanosine (8-OH dG), a marker of oxidative stress, were measured in prostate tissues from normal transition zone and BPH by ELISA. 8-OH dG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis. Nox4 promotes the formation of reactive oxygen species. We therefore created and characterized transgenic mice with prostate specific expression of Nox4 under the control of the prostate specific ARR2PB promoter.ResultsHuman BPH tissues contained significantly higher levels of 8-OH dG than control transition zone tissues and the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG staining were predominantly in the epithelium and were present in a patchy distribution. The total fraction of epithelial staining with 8-OH dG was significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice had increased oxidative DNA damage in the prostate, increased prostate weight, increased epithelial proliferation, and histological changes including epithelial proliferation, stromal thickening, and fibrosis when compared to wild type controls.ConclusionsOxidative stress and oxidative DNA damage are important in the pathogenesis of BPH.
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Project description:To investigate the degree to which expenditures on symptom evaluations vary among urologists and the factors associated with such variation. As the medical and surgical specialists for men with lower urinary tract symptoms (LUTS), urologists provide testing to evaluate symptoms and determine therapy.We developed a cohort of men with an initial urologist visit for benign prostatic hyperplasia (BPH) from a 5% sample of Medicare patients (1999-2007) and established a physician level factor, practice style, as a function of average per patient expenditures. We then determined which AUA BPH guideline elements explained variation in quantity and expenditures for BPH testing, and also examined the impact of patient and physician factors on practice style.A nearly 15-fold variation in urologists' average per-patient expenditures existed ($35 to $527 per month; Median $92). Practice styles were associated with physician (P < .01 all examined variables) and patient (P < .01 for comorbidity, race/ethnicity, and socioeconomic status) factors. Guideline recommended care was provided at lower rates by the lowest expenditure urologists compared with middle- to highest-intensity urologists (P < .01). Practice style variations were attributable mainly to differences in tests characterized by the guidelines as optional and not-recommended (P < .01).Expenditures for BPH evaluations vary substantially by geography, practice setting, and experience and are accounted for largely by differences in the use of optional and not-routinely recommended tests. Greater standardization could enhance patient care and reduce health care costs.
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Project description:In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT1A receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2H-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT1A receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0.
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