Interstitial cystitis/bladder pain syndrome is an uncommon but potentially devastating pelvic pain disorder affecting both women and men. This condition is often confusable and comorbid with other pelvic pain disorders. Although our understanding of the underlying pathophysiology is growing, the exact longitudinal course by which peripheral and central aberrations involving the bladder mucosa, peripheral inflammation, and central dysregulation of bladder sensitivity create painful bladder symptoms remains an area in need of further study. Only a limited number of drugs have been approved for treatment by the Food and Drug Administration, and overall durable efficacy of the many treatments reviewed in recent American Urological Association guidelines remains suboptimal, making awareness, early diagnosis, and use of effective treatments early in the disease course, where neural changes may still be reversible, imperative.
Introduction Scientific research on the effects of marijuana on sexual functioning in women, including libido, arousal, orgasm, and satisfaction, is limited. Aim To evaluate women’s perceptions of the effect of marijuana use before sexual activity. Methods A cross-sectional design, from March 2016–February 2017, within a single, academic, obstetrics and gynecology practice, was performed. Patients were given a questionnaire at their visit and asked to complete it anonymously and place it in a locked box after their visit. Main Outcome Measures The primary outcome was satisfaction in the sexual domains of drive, orgasm, lubrication, dyspareunia, and overall sexual experience. The secondary outcome was the effect of the frequency of marijuana use on satisfaction. Results Of the 373 participants, 34.0% (n = 127) reported having used marijuana before sexual activity. Most women reported increases in sex drive, improvement in orgasm, decrease in pain, but no change in lubrication. After adjusting for race, women who reported marijuana use before sexual activity had 2.13 higher odds of reporting satisfactory orgasms (adjusted odds ratio = 2.13; 95% CI = 1.05, 4.35) than women who reported no marijuana use. After adjusting for race and age, women with frequent marijuana use, regardless of use before sex or not, had 2.10 times higher odds of reporting satisfactory orgasms than those with infrequent marijuana use (adjusted odds ratio = 2.10; 95% CI = 1.01–4.44). Conclusion Marijuana appears to improve satisfaction with orgasm. A better understanding of the role of the endocannabinoid system in women is important, because there is a paucity of literature, and it could help lead to development of treatments for female sexual dysfunction. Lynn BK, López JD, Miller C, et al. The Relationship between Marijuana Use Prior to Sex and Sexual Function in Women. Sex Med 2019;7:192–197.
Cigarette smoking is an environmental risk factor associated with a variety of pathologies including cardiovascular disease, inflammation, and cancer development. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease with multiple etiological contributors and risk factors associated with its development, including cigarette smoking. Previously, we determined that cigarette smoking was associated with bladder wall accumulation of platelet activating factor (PAF), a potent inflammatory mediator that facilitates transendothelial cell migration of inflammatory cells from the circulation. PAF has been shown to reduce expression of tight junctional proteins which could ultimately lead to increased urothelial cell permeability. In this study, we observed that cigarette smoke extract (CSE) treatment of human urothelial cells increases PAF production and PAF receptor expression and reduces wound healing ability. After exposure to cigarette smoke for 6 months, wild‐type C57BL/6 mice displayed urothelial thinning and destruction which was not detected in iPLA 2 β −/− (enzyme responsible for PAF production) animals. We also detected increased urinary PAF concentration in IC/BPS patients when compared to controls, with an even greater increase in urinary PAF concentration in smokers with IC/BPS. These data indicate that cigarette smoking is associated with urothelial cell damage that may be a result of increased PAF‐PAF receptor interaction. Inhibition of iPLA 2 β activity or blocking of the PAF‐PAF receptor interaction could serve as a potential therapeutic target for managing cigarette smoke‐induced bladder damage.
Several methods were developed for the solid-phase synthesis (SPPS) of coloured peptides and peptide libraries. At first a bifunctional red compound, 4-(4-(N-ethyl-N-(3-(tert-butyloxycarbonyl)aminopropyl)amino)phenylazo)be nzoic acid (Boc-EPAB), was coupled with chloromethyl resin to obtain a new solid support suitable for SPPS using Boc chemistry. Peptides synthesized on this coloured resin had the chromophore at their C-termini. N-terminally coloured peptides were synthesized on a traditional solid support, coupled with chromophoric carboxylic acid before cleavage. A model pentapeptide, Phe-Ala-Val-Leu-Gly, and its ten derivatives were synthesized and their properties studied. It was found that the presence of chromophores decreases the water solubility of peptides. However, insertion of solubilizing tags (penta-lysine sequences or polyoxyethyl chains) into the molecule of any coloured derivative resulted in enhancement of the solubility. The RP-HPLC hydrophobicity indexes (phi0) of the coloured peptides were also determined because phi0 values are closely related to their water solubility. A coloured pentapeptide library was synthesized using the portioning-mixing method. Each component of this library contained the red azo dye (EPAB) and the penta-lysine tag. Before the last coupling step the samples were not mixed. All of the 19 sub-libraries obtained after cleavage were readily soluble in water, giving intense red solutions. The effect of chromophore (EPAB) and/or penta-lysine solubilizing tag on the biological activity was also studied. Potencies of the bovine neurotensin 8-13 fragment and its different coloured and penta-lysine derivatives were compared in isolated longitudinal muscle strips of guinea pig ileum. It was shown that the hexapeptide with penta-lysine tag had almost the same activity as the 8-13 fragment itself. The activity of the EPAB-derivative was found to be rather low. However, the presence of the solubilizing tag in the coloured hexapeptide compensated the negative effect of the chromophore.
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