Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

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Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Infertility affects an estimated 15% of couples globally, amounting to 485 million couples Males are found to be solely responsible for 20-30% of infertility cases and contribute to 50% of cases overall However, this number does not accurately represent all regions of the world Indeed, on a global level, there is a lack of accurate statistics on rates of male infertility Our report examines major regions of the world and reports rates of male infertility based on data on female infertility Our search consisted of systematic reviews, meta-analyses, and population-based studies by searching the terms “epidemiology, male infertility, and prevalence” We identified 16 articles for detailed study We typically used the assumption that 50% of all cases of infertility are due to female factors alone, 20-30% are due to male factors alone, and the remaining 20-30% are due to a combination of male and female factors Therefore, in regions of the world where male factor or rates of male infertility were not reported, we used this assumption to calculate general rates of male factor infertility Our calculated data showed that the distribution of infertility due to male factor ranged from 20% to 70% and that the percentage of infertile men ranged from 2·5% to 12% Infertility rates were highest in Africa and Central/Eastern Europe Additionally, according to a variety of sources, rates of male infertility in North America, Australia, and Central and Eastern Europe varied from 4 5-6%, 9%, and 8-12%, respectively This study demonstrates a novel and unique way to calculate the distribution of male infertility around the world According to our results, at least 30 million men worldwide are infertile with the highest rates in Africa and Eastern Europe Results indicate further research is needed regarding etiology and treatment, reduce stigma & cultural barriers, and establish a more precise calculation

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A unique view on male infertility around the globe

Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.

/pdf/oxidative-stress-and-male-infertility-a-clinical-perspective-2nu3kdi0jn.pdf

Oxidative stress and male infertility—a clinical perspective

Fertility and infertility: Definition and epidemiology.

Introduction Infections of the urinary tract (UTIs) pose a serious health problem for patients at high cost for society. UTIs are also the most frequent healthcare associated infections. E. coli is the predominating pathogen in uncomplicated UTIs while other Enterobacteriaceae and Enterococcus spp are isolated in higher frequency in patients with urological diseases. The present state of microbial resistance development is alarming and the rates of resistance are related to the amount of antibiotics used in the different countries. Particularly worrisome is the increasing resistance to broad spectrum antibiotics. It is thus essential to limit the use of antibiotics in general and fluoroquinolones and cephalosporins in particular, especially in uncomplicated infections and asymptomatic bacteriuria.

/pdf/guidelines-on-urological-infections-23ooqjk2xp.pdf

Guidelines on Urological Infections

https://uroweb.org/wp-content/uploads/Jungwirth-A-et-al-Eur-Urol-2012-622342-EAU-Guidelines-on-Male-Infertility-the-2012-update.pdf

European Association of Urology Guidelines on Male Infertility: The 2012 Update

Reactive oxygen species (ROS) are involved in a variety of pathophysiological conditions of the testis, and oxidative stress is known to inhibit ovarian and testicular steroidogenesis The site of ROS-mediated inhibition of steroidogenesis in the corpus luteum and MA-10 tumor Leydig cells was shown to be the hormone-sensitive mitochondrial cholesterol transfer step The purpose of this study was to examine the effects of ROS on steroidogenic acute regulatory (StAR) protein in MA-10 cells and determine the extent to which MA-10 cell mitochondria are sensitive to oxidative stress cAMP-stimulated progesterone production was inhibited in a dose-dependent manner in MA-10 cells exposed to H(2)O(2) StAR protein, but not mRNA levels, was decreased in parallel to changes in progesterone production Even at the highest concentrations of H(2)O(2) tested, there was no effect on P450 side-chain cleavage enzyme protein levels Oxidative stress from exposure to exogenous xanthine oxidase and xanthine resulted in the inhibition of both progesterone production and StAR protein expression The mature 30- and 32-kDa intramitochondrial forms of StAR were decreased relative to the 37-kDa extramitochondrial precursor form of StAR, indicating that the ROS-mediated inhibition of StAR protein was due, in part, to the inhibition of mitochondrial import and processing Vital staining with the fluorescent dye tetramethylrhodamine ethyl ester was used to visualize changes in the mitochondrial electrochemical gradient-dependent membrane potential (Deltapsim) ROS caused a significant dissipation of Deltapsi(m) and time-dependent loss of tetramethylrhodamine ethyl ester fluorescence The inhibitory effects of H(2)O(2) were transient There was no evidence for ROS-induced cell death, and following H(2)O(2) removal in the presence of continuous treatment with 8-bromo-cAMP, StAR protein levels and progesterone production were restored In addition, there was no loss of cell viability following treatment with H(2)O(2) or xanthine/xanthine oxidase as determined by trypan blue exclusion H(2)O(2) did not cause a significant decrease in total cellular ATP levels These data indicate that oxidative stress-mediated perturbation of the mitochondria and dissipation of Deltapsi(m) results in the inhibition of StAR protein expression and its import, processing, and cholesterol transfer activity These findings confirm earlier studies demonstrating the requirement for maintenance of an intact Deltapsi(m) for StAR protein function in cholesterol transport The significant reduction in the 32- to 30-kDa mature forms of StAR, cessation of cholesterol transport, and loss of Deltapsi(m) are consistent with mitochondrial perturbation because of oxidative stress This mechanism likely contributes to a host of pathophysiological events evident in testicular disorders such as infection, reperfusion injury, aging, cryptorchidism, and varicocele

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Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis.

52. Berger RE. Epididymitis. In: Holmes KK, Mardh PA, Sparling PF et al. (eds). Sexually Transmitted Diseases. New York: McGraw-Hill, 1984, pp. 650-662. 53. Weidner W, Schiefer HG, Garbe C. Acute nongonococcal epididymitis. Aetiological and therapeutic aspects. Drugs 1987;34 (Suppl 1):111-117. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3481311&do

/pdf/guidelines-on-male-infertility-36fa8yqqv3.pdf

Guidelines on Male Infertility

Inflammatory disease has been established to affect male reproductive function and fertility. Relevant inflammatory diseases include general and chronic infectious diseases as well as localized acute or chronic infections of the male genitourinary tract. Male accessory gland infections account for almost 15% of all cases of male infertility seen in infertility clinics while fertility usually is not a clinical objective among patients with acute systemic infections such as Gram-negative sepsis. Infections of the male accessory glands frequently are associated with increased counts of white blood cells in semen and elevated levels of proinflammatory cytokines in semen and the testis. There is a mounting body of evidence that demonstrates the importance of cytokines and chemokines in the regulation of testicular and glandular function during pathophysiological states as well as under normal physiological conditions when cytokines act as growth and differentiation factors. The purpose of this review is to examine the role of cytokines in the regulation of steroidogenesis and spermatogenesis in the testis under physiological and pathophysiological conditions and considers clinical investigations that help to improve the evaluation and treatment of male infertility.

Role of cytokines in testicular function.

The influence of E. coli on human sperm motility was studied in vitro. Semen samples were prepared by a swim-up technique and adjusted to 22 x 10(6) spermatozoa/ml. Samples were then inoculated with different concentrations of a uropathogenic strain of E. coli, serotype 06, with initial sperm/bacteria ratios varying between 10:1 and 10000:1. Motion parameters were analysed by computer-aided motility analysis directly, and 2, 4 and 6 h after inoculation. In a second series of experiments, bacterial replication was inhibited by addition of chloramphenicol. In a third series, the effect of E. coli culture filtrates on sperm motility was investigated. The direct inhibitory effect of E. coli on progressive motility of spermatozoa was found to depend upon the bacterial concentration. A distinct inhibitory effect was observed only at a sperm/bacteria ratio of approximately 1, achieved by growth of E. coli during the experiments. For modality of motion, no distinct changes were observed. When growth of bacteria was prevented by chloramphenicol, no inhibitory effect on sperm motility was detected. Sperm motility was not inhibited by E. coli culture filtrates. Analysis by electron microscopy revealed multiple adhesions of E. coli to spermatozoa, causing variable ultrastructural damage as probable morphological correlates of immobilization.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2605.1996.tb00475.x

Thorsten Diemer

Papers

European Association of Urology Guidelines on Male Infertility: The 2012 Update

Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis.

Guidelines on Male Infertility

Role of cytokines in testicular function.

Influence of Escherichia coli on motility parameters of human spermatozoa in vitro