Effects of Fruit and Vegetable Polyphenols on the Glycemic Control and Metabolic Parameters in Type 2 Diabetes Mellitus: A Review.

The high prevalence of diabetes in recent decades has been associated with lifestyle changes and dietary habits correlated with economic development. Fruits and vegetables are a vital source of nutraceuticals and components of the healthy diet recommended in the medical nutrition therapy for type 2 diabetes mellitus (T2DM) to prevent hyperglycemia and related complications. They are low in calories and rich in dietary fiber, consist of many polyphenols, and are an essential component of a healthy lifestyle. Recently, researchers have developed a significant interest in understanding the effects of polyphenols (flavonoids and non-flavonoids) on blood glucose levels. In this review, the authors summarize the effects of polyphenols commonly found in the fruits and vegetables, such as resveratrol and anthocyanins, on the glycemic control and metabolic parameters, based on human clinical trials. Significant reductions in fasting blood glucose, glycated hemoglobin, and low-density lipoprotein cholesterol levels were reported after resveratrol, anthocyanin, and naringin were administered to patients with prediabetes and diabetes. Decreased insulin levels were observed after resveratrol intervention but not with the other types of polyphenols. These effects of polyphenolic compounds on the glycemic and metabolic parameters might be mediated by multiple pathophysiological mechanisms, such as activating regulator proteins to increase insulin signaling and eventually suppress insulin resistance. The benefits of certain polyphenols on T2DM remain ambiguous; therefore, further studies, especially clinical trials, are required to substantiate the available evidence.

Moringa oleifera Lam. leaf extracts reverse metabolic syndrome in Sprague Dawley rats fed high-fructose high fat diet for 60-days.

Background: Moringa oleifera Lam. has been used traditionally for the treatment of different cardio-metabolic disorders. So, the aim was to assess its leaf extracts in metabolic syndrome rat model.Methods: Out of the total 36-rats, 6 rats were given normal matched diet (NMD) while the rest were provided high-fat diet and 20% fructose (HFD-20%F). Moringa oleifera leaf extracts were administered orally for 30 days. Body weight, blood glucose, BMI, blood pressure, lipids, insulin, insulin resistance, MCP-1, visceral fat and liver weight were evaluated.Results: Sixty-days feeding with HFD-20%F produced the metabolic syndrome features like hyperinsulinemia, insulin resistance, and increase in low-density lipoprotein (LDL), visceral fat, and liver weight significantly (p<.05) than the rats receiving (NMD). Moringa oleifera treatment for 30 days significantly provided the mitigation against metabolic syndrome features.Conclusion: Moringa oleifera Lam. leaf extract might be a good alternative herbal choice in the treatment of metabolic syndrome disease.

Formulation and In Vivo Evaluation of a Solid Self-Emulsifying Drug Delivery System Using Oily Liquid Tocotrienols as Model Active Substance.

Self-emulsifying drug delivery systems (SEDDS) can improve the oral bioavailability of poorly water-soluble drugs. Solid self-emulsifying drug delivery systems (s-SEDDS) offer several advantages including improved drug stability, ease of administration, and production. Most compounds employed in developing s-SEDDS are solid in nature, with a high amount of surfactants added. The aim of this study was to develop an s-SEDDS using a tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The solid formulation was developed using magnesium aluminosilicate as the carrier with 70% TRF and 30% surfactants (poloxamer and Labrasol®). The formulation showed good self-emulsification efficiency with stable emulsion formed, excellent powder flowability, and small emulsion droplet size of 210-277 nm. The s-SEDDS with combined surfactants (poloxamer and Labrasol®) showed a faster absorption rate compared to preparations with only a single surfactant and enhanced oral bioavailability (3.4-3.8 times higher) compared to the non-self-emulsifying oily preparation when administered at a fasted state in rats. In conclusion, an s-SEDDS containing a high amount of TRF was successfully developed. It may serve as a useful alternative to a liquid product with enhanced oral bioavailability and the added advantage of being a solid dosage form.

Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis.

There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92-1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77-1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88-1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85-0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98-1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.

Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats.

Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.

Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation.

INTRODUCTION: Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers. METHODS: Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats' back skin. RESULTS: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel. CONCLUSION: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.

In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

BACKGROUND: The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. METHODS: Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. RESULTS: The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. CONCLUSION: Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial.

Importance: Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities. Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy. Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited. Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 µg thrice daily, in both groups. Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result. Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses. Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration. Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.

Effect of pulsed magnetic stimulation on quality of life of female patients with stress urinary incontinence: an IDEAL-D stage 2b study.

INTRODUCTION AND HYPOTHESIS: We evaluated the effects of pulsed magnetic stimulation (PMS) on overall and different aspects of quality of life (QoL) in female patients with stress urinary incontinence (SUI). METHODS: This study involved 120 female SUI subjects aged ≥21 years old randomized to either active or sham PMS. Treatment involved two PMS sessions per week for 2 months (16 sessions). After 2 months, subjects could opt for 16 additional sessions regardless of initial randomization. The primary response criterion was a 7-point reduction in the total score of the International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol) questionnaire. Follow-ups were conducted at months 1, 2, 5, 8, and 14. RESULTS: At 2 months, 35 out of 60 (58%) subjects in the active arm and 21 out of 60 (21%) in the sham arm were treatment responders (≥7-point reduction) (p = 0.006). There was a significant difference in changes in the mean ± SE ICIQ-LUTSqol total score between the active and sham arms (Mdiff = -8.74 ± 1.25 vs -4.10 ± 1.08, p = 0.006). At 1-year post-treatment, regardless of number of PMS sessions (16 or 32 sessions), subjects who received active PMS (63 out of 94, 67%) were more likely to be treatment responders compared with subjects who did not receive any active PMS (3 out of 12, 25%; p < 0.001). The impact of PMS treatment was the greatest on the "physical activities" domain. CONCLUSIONS: PMS resulted in significant short- and long-term improvements in overall and various physical, social, and psychological aspects of QoL.

Sexual Function in Couples With or Without Female Incontinent Partners: Correlates and Predictors.

OBJECTIVE: To evaluate the correlation between sexual function of couples with and without stress urinary incontinence (SUI) partners, and to identify predictors of poor sexual function. MATERIALS AND METHODS: A cross-sectional survey was conducted involving sexually active women with or without SUI aged at least 21 years old, and their respective partners. Both partners completed the Golombok Rust Inventory of Sexual Satisfaction (GRISS), a 28-item multidimensional measure with separate forms for male and female designed to assess sexual satisfaction of both partners. Spearman rank correlation coefficient was used to analyze bivariate association, whereas multiple regression analysis was used to identify predictors for overall sexual function as measured using GRISS score. RESULTS: Sixty-six couples with SUI partners and 95 couples with continent partners were recruited. Overall GRISS scores and thus sexual function of men and women were strongly correlated. The correlation coefficient was higher in couples with SUI partners (r = 0.702, P <.001) compared with couples with continent partners (r = 0.629, P <.001), indicating a stronger correlation in the sexual function of couples with SUI partners. In multivariate analysis, poorer sexual function (lower GRISS score) in women, increasing age, and less frequency of sexual intercourse were significant predictors of poorer overall GRISS score in couples (P <.001). CONCLUSION: Female sexual function is strongly correlated with male partners' sexual function, with a stronger correlation observed in couples with SUI partners. Poorer sexual function in women, increasing age, and less frequency of sexual intercourse are predictive of poorer sexual function in a couple.

The Impact of Stress Urinary Incontinence on Individual Components of Quality of Life in Malaysian Women.

OBJECTIVE: To assess the impact of stress urinary incontinence (SUI) on individual components of quality of life (QoL) using both condition-specific and generic questionnaires, and to compare the results of the 2 instruments with a control group. METHODS: Women with or without SUI aged ≥21 years old were recruited. Subjects completed the International Consultation of Incontinence-Urinary Incontinence Short Form (ICIQ-UI-SF), International Consultation of Incontinence-Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and EQ-5D questionnaires. RESULTS: A total of 120 women with SUI and 145 controls participated. The ICIQ-LUTSqol total score (mean ± standard deviation) was significantly higher in the SUI group (38.96 ± 10.28) compared with the control group (20.78 ± 2.73) (P <.001). When adjusted for significant confounders, the SUI group continued to have significantly poorer QoL compared with the control group (P <.001). The negative effect of SUI on "physical activities" and "jobs" were the 2 most frequently reported and burdensome components of the ICIQ-LUTSqol, with approximately 50% of women with SUI affected "moderately" or "a lot." When measured using the EQ-5D questionnaire, there were significantly higher percentages of patients with SUI who had problems with usual activities, pain or discomfort, and anxiety or depression (P <.05). CONCLUSION: Women suffering from SUI have significantly poorer QoL compared with continent women when measured using both condition-specific and generic QoL measures. Clinicians should pay closer attention to the impact of SUI on individual components of QoL, particularly limitations on physical activities and jobs, which were the 2 most impairing and frequently reported components of QoL.

Patients' perception and satisfaction with pulsed magnetic stimulation for treatment of female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: We evaluated patients' perception and satisfaction with nonsurgical pulsed magnetic stimulation (PMS) for treatment of female stress urinary incontinence (SUI) in a randomized, double-blind, sham-controlled trial. METHODS: Women with SUI (n = 120) were randomized to either active or sham PMS for 8 weeks (twice/week). Patients answered seven questions on their perception and acceptability, each measured on a 5-point Likert scale. Treatment satisfaction was assessed using two parameters: (i) the single-item question "Overall, please rate how satisfied you are with the treatment" and (ii) Patient Global Impression of Improvement (PGI-I). All adverse events were documented. RESULTS: A total of 115 patients completed treatments (active: n = 57, sham: n = 58). There were no significant differences between groups in all parameters regarding perception and acceptability (p > 0.05). In terms of treatment satisfaction, a significantly higher proportion of patients in the active group (n = 47/57, 82.4%) were either mostly or completely satisfied compared with those in the sham group (n = 27/58, 46.6%) ((p = 0.001). Similarly, a statistically significantly higher percentage of patients in the active group (n = 39/57, 68.4%) felt much or very much better compared with patients in the sham group (n = 11/58, 19.0%) as measured using the PGI-I (p < 0.001). Three (5.3%) patients in the active group and five (8.6%) in the sham group experienced adverse events (p = 0.72). Regardless of treatment arms, 109 (94.8%) patients would not consider surgical options even if they required further treatment for their condition. CONCLUSION: PMS was well accepted, well tolerated, and resulted in a high treatment satisfaction among women with SUI.

Effect of Pulsed Magnetic Stimulation on Sexual Function in Couples With Female Stress Urinary Incontinence Partners.

We prospectively evaluated the effects of pulsed magnetic stimulation (PMS) on sexual function of couples with stress urinary incontinence (SUI) partners. Female SUI subjects received 16 or 32 biweekly PMS sessions, depending on treatment response. Prior to, immediately after, and at 6-months posttreatment, couples completed the Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire. Fifty-three (80.3%) of 66 couples completed reassessments. Based on the overall GRISS score, there were significant improvements in sexual function in both female subjects (Mdiff -5.05, SE 1.34, p = 0.001) and their partners (Mdiff -3.42, SE 1.24, p = 0.026). Our findings suggest that PMS improved sexual function of SUI patients and their partners.

Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid-Based Solid Dispersion to Improve Rat Sperm Count.

Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p < 0.001) and fourfold (p < 0.001) higher sperm count than did TAF2-treated and vehicle-treated (control) rats, respectively. The study also demonstrated no significant in vitro ileal absorption changes of the quassinoids by P-gp efflux inhibitors and concentration change or secondary metabolite formation upon in vitro incubation with rat liver homogenates, suggesting that P-gp-mediated efflux and presystemic metabolism were not limiting their bioavailability. Further study on orally TAF2-treated rats confirmed that the area under the curve and bioavailability curve of each quassinoid in the absence and presence of ketoconazole were unchanged. Copyright © 2017 John Wiley & Sons, Ltd.

Validity and Reliability of the Golombok Rust Inventory of Sexual Satisfaction in Couples with Incontinent Partners.

There is currently no published information on the validity and reliability of the Golombok Rust Inventory of Sexual Satisfaction in the Asian population, specifically in patients with stress urinary incontinence, which limits its use in this region. Our study aimed to evaluate the psychometric properties of this questionnaire in the Malaysian population. Ten couples were recruited for the pilot testing. The agreement between the English and Chinese or Malay versions were tested using the intraclass correlation coefficients, with results of more than 0.80 for all subscales and overall scores indicating good agreement. Sixty-six couples were included in the subsequent phase. The following data are presented in the order of English, Chinese, and Malay. Cronbach's alphas for the male total score were 0.82, 0.88, and 0.95. For the female total score, Cronbach's alphas were 0.76, 0.78, and 0.88. Intraclass correlation coefficients for the male total score were 0.93, 0.94, and 0.99, while intraclass correlation coefficients for the female total score were 0.89, 0.86, and 0.88. In conclusion, the English, Chinese, and Malay versions each proved to be valid and reliable in our Malaysian population.

Pulsed Magnetic Stimulation for Stress Urinary Incontinence: 1-Year Followup Results.

PURPOSE: Despite significant differences in success rates between surgical and nonsurgical treatments for female stress urinary incontinence, a few cross-sectional surveys showed that most patients still prefer the latter. We evaluated the efficacy of the under studied nonsurgical treatment using pulsed magnetic stimulation for female stress urinary incontinence. MATERIALS AND METHODS: This randomized, double-blind, sham controlled study was performed in 120 female subjects at least 21 years old with stress urinary incontinence. Treatment involved pulsed magnetic stimulation for 2 sessions per week for 2 months (16 sessions). After 2 months, subjects could opt for 16 additional sessions regardless of initial randomization. The primary response criterion was a 5-point reduction in the ICIQ-UI SF (International Consultation on Incontinence Questionnaire for Urinary Incontinence-Short Form) score. Key secondary response criteria included objective and subjective cure, supplemented by other secondary criteria. Followups were performed at months 1, 2, 5, 8 and 14. RESULTS: At 2 months 45 of 60 subjects (75%) in the active arm vs 13 of 60 (21.7%) in the sham arm were treatment responders (p <0.001). After 2 months 24 subjects (40%) in the active arm and 41 (68%) in the sham arm elected additional active pulsed magnetic stimulation. At 14 months, subjects who received 32 sessions of active pulsed magnetic stimulation had the highest percentage of treatment responders (18 of 24 or 75.0%), followed by those who received 16 sessions (26 of 36 or 72.2% and 28 of 41 or 68.3%) and those who did not receive any active pulsed magnetic stimulation (4 of 19 or 21.1%) (p <0.001). CONCLUSIONS: The encouraging long-term response rates show that pulsed magnetic stimulation is an attractive nonsurgical alternative for patients who do not want to undergo surgery.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials.

Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.

Effect of Stress Urinary Incontinence on the Sexual Function of Couples and the Quality of Life of Patients.

PURPOSE: Studies of the effects of stress urinary incontinence on the sexual function of couples are scarce. We prospectively evaluated couple sexual function and the relationship between sexual function and quality of life. We also compared quality of life in females with vs without stress urinary incontinence. MATERIALS AND METHODS: Sexually active females at least 21 years old with or without stress urinary incontinence and their partners were recruited for study. To assess sexual function the couples completed GRISS (Golombok Rust Inventory of Sexual Satisfaction) and a 1-item question on overall sexual experience, "Over the past 4 weeks, how satisfied have you been with your overall sexual life?" Additionally, females completed ICIQ-LUTSqol (International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life) to assess quality of life. RESULTS: For sexual function assessment 66 of 134 couples with (49.3%) and 95 of 176 without (54.0%) stress urinary incontinence were recruited. Females with stress urinary incontinence had lower overall sexual function, lower frequency of sexual intercourse, less satisfaction (each p <0.001) and higher avoidance behavior (p = 0.026). Partners of females with stress urinary incontinence had more problems with erectile dysfunction (p = 0.027), less satisfaction (p = 0.006) and lower frequency of sexual intercourse (p = 0.001) but no difference in overall GRISS score (p = 0.093). Couples with stress urinary incontinence had poorer overall sexual experience (p <0.05). Females with stress urinary incontinence had poorer quality of life than those without stress urinary incontinence (120 of 134, response rate 89.6% vs 145 of 176, response rate 82.4%, p <0.001). Sexual function and quality of life did not significantly correlate (r = 0.001, p = 0.997). CONCLUSIONS: Stress urinary incontinence in females is negatively associated not only with female quality of life and sexual function but also with partner sexual function.

Solid Lipid Nanoparticles of Atovaquone Based on 2(4) Full-Factorial Design.

Solid lipid nanoparticles of atovaquone (ATQ-SLN) were prepared by high shear homogenization method using tripalmitin, trilaurin, and Compritol 888 ATO as the lipid matrices and Phospholipon 90H, Tween 80, and poloxamer 188 as the surfactants. Optimization of the formulations was conducted using 6 sets of 2(4) full-factorial design based on four independent variables that were the number of homogenizing cycles, concentration of the lipid, concentration of the co-surfactant, and concentration of the main surfactant. The dependent variables were particle size and polydispersity index (PdI). The homogenizing cycles showed a negative influence on the dependent variables which reduced both the particle size and the PdI value. Moreover, a combination of certain percentages of the main surfactant and co-surfactant also showed a negative influence that reduced both the particle size and PdI value. Selected formulations from each design were further characterized for the entrapment efficiency and yield. The optimised formulation of ATQ-SLN consisted of trilaurin, Phospholipon 90H and Tween 80 with a particle size of 89.4 ± 0.2 nm and entrapment efficiency of 83.0 ± 1.7%. The in-vitro release evaluation of the formulation showed a complete and immediate release of ATQ from the SLN that could be a solution to improve the poor aqueous solubility and hence poor bioavailability of the drug.

Magnetic stimulation for stress urinary incontinence: study protocol for a randomized controlled trial.

BACKGROUND: There is currently a lack of randomized, sham-controlled trials that are adequately powered, using validated outcomes, to allow for firm recommendations on the use of magnetic stimulation for stress urinary incontinence. We report a protocol of a multicenter, randomized, double-blind, sham-controlled parallel-group trial to evaluate the efficacy of magnetic stimulation for stress urinary incontinence. METHODS/DESIGN: One hundred twenty subjects with stress urinary incontinence will be randomized in a 1:1 allocation to either active or sham magnetic stimulation using computer-generated, permuted blocks of variable sizes. Subjects will receive 2 sessions of magnetic stimulation per week for 8 weeks (16 sessions total). The primary outcome is the improvement in severity of involuntary urine loss based on the International Consultation on Incontinence Questionnaire for Urinary Incontinence Short Form at the end of treatment sessions compared with baseline. Secondary outcomes include cure, stress urinary incontinence-related symptoms (incontinence episode frequency, urine loss in 1-hour pad test, pelvic floor muscle strength) and health-related quality of life (Patient Global Impression of Improvement, International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life and EQ-5D). The safety of magnetic stimulation will also be assessed. Besides evaluation of clinical treatment effectiveness, cost-effectiveness analysis using patient-reported outcomes will be performed. DISCUSSION: This trial is designed to provide pending outcome information on this non-invasive treatment option. We intend to acknowledge the existing flaws in previous clinical trials and determine conclusively whether magnetic stimulation is effective for stress urinary incontinence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01924728. Date of Registration: 14 August 2013.