12-week Serum Research Articles

Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration

The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values.The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause.

Effect of 5/6 Nephrectomized Rat Serum on Epithelial-to-Mesenchymal Transition In Vitro

Objective: To investigate whether the 5/6 nephrectomized (5/6Nx) rats’ 12-week serum could lead to tubular epithelial-to-mesenchymal transition (EMT) and its molecular mechanism, so as to probe the potential stimulation from circulation in chronic progressive kidney disease. Methods: A total of 24 Sprague Dawley (SD) rats were randomly divided into two groups: sham operation group (sham group) and 5/6Nx group. Rats were killed 12 weeks after surgery to obtain 5/6Nx rats’ 12-week serum. Then we detected the expression of E-cadherin in renal tubular epithelial cells of the remaining kidney and we investigated whether the 12th week serum of 5/6Nx rats could cause HK-2 (human kidney proximal tubular cell line) cells to transdifferentiate into fibroblasts. Results: Our data confirmed that E-cadherin expression decreased significantly in the remaining kidney at 12 weeks, and the 5/6Nx rats’ 12-week serum could suppress E-cadherin protein and mRNA expression (p < 0.05). We also found that the 5/6Nx rats’ 12-week serum could upregulate ZEB1, β-catenin, and wnt3 protein expression (p < 0.05). Conclusions: Our results demonstrated that the 5/6Nx rats’ 12-week serum could suppress the expression of E-cadherin in HK-2 cells. It was partially through modulating the increase of ZEB1. The loss of E-cadherin could lead β-catenin to localize to the cytoplasm and nucleus, and feed into the Wnt signaling pathway. It means that the pathogenic serum in chronic kidney disease (CKD) plays an important role in the loss of renal function and turns to be a new avenue of research with potential clinical implications.

Predictive Factors for Response to Peginterferon-Alpha and Ribavirin Treatment of Chronic HCV Infection in Patients Aged 65 Years and More

Elderly patients with chronic hepatitis C virus (HCV) infection represent an understudied population, and little is known regarding the predictive factors for sustained virological response (SVR) to antiviral therapy in these patients. To evaluate the efficacy of pegylated interferon (PEG-IFN) and ribavirin therapy in chronic HCV patients aged 65years, and identify pre- and on-treatment predictors of SVR. We studied 57 patients aged ≥65years who underwent PEG-IFN and ribavirin treatment, evaluating the SVR rate and its association with pre-treatment demographic, clinical, biochemical, and virological parameters. Furthermore, we assessed whether 12-week serum HCV-RNA assessment might predict SVR. A SVR was obtained in 25 patients (45%). The only pre-treatment predictor of SVR was HCV genotype 2 and 3 (P=0.02). A positive serum HCV-RNA or a decline in viral load ≤2log(10) at week 12 had 100% negative predictive value for SVR. No major liver-related events or deaths occurred during therapy. Treatment was discontinued due to side effects-mainly cardiovascular-in 10 patients (17%). Pre- and on-treatment virological parameters can be used to identify elderly patients who are more likely to obtain a SVR to standard-of-care antiviral therapy for chronic HCV infection.

GUEST EDITORIAL: Female Sexual Dysfunction and the Central Nervous System

The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values.The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause.

The effect of multiple transfers of immune serum on maturingSchistosoma bovis infections in calves

To investigate the role of humoral factors in immunity, serum from cattle with naturally acquired immunity to Schistosoma bovis was injected intraperitoneally into calves that had been infected 4 weeks earlier with 10,000 S. bovis cercariae. Serum was injected weekly until 12 weeks post-infection to a total of 4,500 ml per calf and controls received normal serum or saline. No significant difference in worm or in faecal or tissue egg counts were seen in the three groups of recipients in spite of the observation that the serum donors had proved highly resistant to experimental challenge. In a second experiment, pre-infection or 4-, 8- or 12-week post-infection serum from donors given a single experimental infection with 10,000 S. bovis cercariae was injected intraperitoneally into groups of calves that had been infected 4 weeks earlier with 20,000 S. bovis cercariae. Injections were given weekly up to week 10 post-infection to a total of 2000-3500 ml serum per calf. In calves injected with immune serum there was a reduction in faecal and tissue egg counts and in the numbers of worms recovered as compared with the controls. In recipients of 8- and 12-week serum the reductions in faecal and tissue egg counts were higher than those in worm recovery, suggesting that 8- and 12-week post-infection sera contained factors capable of causing, in addition to worm death, suppression of worm fecundity. This provides further evidence of the importance of fecundity suppression in immunity to schistosomiasis.