Caulerpa lentillifera polysaccharides enhance the immunostimulatory activity in immunosuppressed mice in correlation with modulating gut microbiota.

In this study, the immunostimulatory activity of Caulerpa lentillifera polysaccharides (CLP) was elucidated in cytoxan (CTX)-induced immunosuppressed BALB/c mice. The results showed that CLP ameliorated the CTX-evoked damage to body weight, colon length and thymus/spleen indexes and enhanced the secretions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and superoxidase dismutase (SOD) in serum and thymic, splenic and colonic tissues of the immunosuppressed mice. Besides, CLP promoted the production of secretory immunoglobulin A (SIgA) and mucin2 in the colonic tissue of the immunosuppressed mice. Associated with the above immunostimulatory effects, CLP positively affected the production of short chain fatty acids (SCFAs) and microbiota diversity and composition, such as improvement in the growth of Lactobacillus, Coriobacteriaceae, Ruminococcaceae, Clostridium_XVIII and Helicobacter, whereas it suppressed the microbial populations of Bacteroides, Barnesiella and Lachnospiraceae. These findings suggested that CLP modulated SCFA production and gut microbiota in the immunosuppressed mice, evoking the colonic mucosal immunity, which might activate the systemic immunity in blood, thymus and spleen. The results could be helpful for understanding the functions of CLP, supporting their potential as novel prebiotics and immunostimulators.

A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values.

OBJECTIVE: Serum concentrations of estradiol (E2) and testosterone (testo) measured by mass spectrometry-based assays should remain below the 95th centile measured at 9.3 pg/mL for E2 and 0.26 ng/mL for testo in normal postmenopausal women in order to avoid the risk of non-physiological systemic exposure to elevated serum concentrations of these two sex steroids. METHODS: Serum E2 and testo, as well as dehydroepiandrosterone (DHEA) and nine of its other metabolites, were measured at 10 time intervals over 24 h on the first and seventh days of daily intravaginal administration of 0.50% (6.5 mg) DHEA by validated mass spectrometry-based assays. RESULTS: No biologically significant change in the individual serum concentrations of E2, testo or DHEA was observed. Most importantly, estrone sulfate (E1-S) and the glucuronidated androgen metabolites also remained within normal values, thus confirming the absence of biologically significant systemic exposure in line with intracrinology. Using data from the literature, comparison is made with serum E2 above normal postmenopausal values following administration of 10-µg E2 tablets. CONCLUSION: While the clinical program on vulvovaginal atrophy has shown the efficacy and safety of intravaginal 6.5 mg of DHEA (prasterone), the present data illustrate in detail the serum levels of the individual sex steroids and their metabolites derived from DHEA. The data obtained are in line with the physiology of intracrinology and confirm an action limited to the vagina as the serum concentrations of all sex steroids are maintained within the normal values of menopause, thus protecting the uterus and most likely other tissues.

p-sulfonated calix[8]arene functionalized graphene as a "turn on" fluorescent sensing platform for aconitine determination.

This work reports a novel method for the determination of aconitine through the competitive host-guest interaction between p-sulfonated calix[8]arene (SCX8) and signal probe/target molecules by using SCX8 functionalized reduced graphene oxide (SCX8-RGO) as a receptor. Three dyes (ST, RhB, BRB) and aconitine were selected as the probe and target molecules, respectively. The formation of SCX8-RGO·ST, SCX8-RGO·RhB, and SCX8-RGO·BRB complexes greatly decreases the fluorescence emission of ST, RhB, and BRB. The aconitine/SCX8 complex possesses a higher binding constant than ST/SCX8, RhB/SCX8, and BRB/SCX8 complexes, thus the dye in the SCX8 cavity can be replaced by aconitine to revert the fluorescence emission of SCX8-RGO·dye, leading to a "switch-on" fluorescence response. The fluorescence intensity of SCX8-RGO·ST, SCX8-RGO·RhB, and SCX8-RGO·BRB complexes increased linearly with increasing concentration of aconitine ranging from 1.0 to 14.0µM, 2.0-16.0µM, and 1.0-16.0µM, respectively. Based on the competitive host-guest interaction, the proposed detection method for aconitine showed detection limits of 0.28µM, 0.60µM, and 0.37µM, respectively, and was successfully applied for the determination of aconitine in human serum samples with good recoveries from 95.1% to 104.8%. The proposed method showed high selectivity for aconitine beyond competitive binding analytes. In addition, the inclusion complex of the SCX8/aconitine was studied by the molecular docking and molecular dynamics simulation, which indicated that the phenyl ester group of the aconitine molecule was included into the SCX8 cavity.

A first-generation physiologically based pharmacokinetic (PBPK) model of alpha-tocopherol in human influenza vaccine adjuvant.

Alpha (α)-tocopherol is a component of a new generation of squalene-containing oil-in-water (SQ/W) emulsion adjuvants that have been licensed for use in certain influenza vaccines. Since regulatory pharmacokinetic studies are not routinely required for influenza vaccines, the in vivo fate of this vaccine constituent is largely unknown. In this study, we constructed a physiologically based pharmacokinetic (PBPK) model for emulsified α-tocopherol in human adults and infants. An independent sheep PBPK model was also developed to inform the local preferential lymphatic transfer and for the purpose of model evaluation. The PBPK model predicts that α-tocopherol will be removed from the injection site within 24h and rapidly transfer predominantly into draining lymph nodes. A much lower concentration of α-tocopherol was estimated to peak in plasma within 8h. Any systemically absorbed α-tocopherol was predicted to accumulate slowly in adipose tissue, but not in other tissues. Model evaluation and uncertainty analyses indicated acceptable fit, with the fraction of dose taken up into the lymphatics as most influential on plasma concentration. In summary, this study estimates the in vivo fate of α-tocopherol in adjuvanted influenza vaccine, may be relevant in explaining its immunodynamics in humans, and informs current regulatory risk-benefit analyses.

The CpG ODNs enriched diets enhance the immuno-protection efficiency and growth rate of Chinese mitten crab, Eriocheir sinensis.

CpG oligodeoxynucleotides (ODNs), the well-known vaccine adjuvant in mammals, have been proved to mount innate immune responses in crustaceans. In the present study, CpG ODNs was employed as supplements in diets to fed crab Eriocheir sinensis, and the changes of immune parameters as well as weight gain were investigated to evaluate its possible application in crab farming. After the crabs were fed with 40 mg/kg and 100 mg/kg CpG ODNs containing diets (designated as C40 and C100 group) for four weeks, the lysozyme activities were significantly enhanced (p < 0.01) in both groups, while the catalase activity was only increased (p < 0.01) in the C40 group. When those crabs were subsequently challenged with Aeromonas hydrophila, the cumulative mortalities in C40 and C100 groups were declined by 10.4% and 10.8% (p < 0.05) compared with that of control group, respectively. Interestingly, the final weights of crabs were increased after four weeks' feeding of CpG ODNs, and the percentage of weight gain in C40 group reached 124.5 ± 14.2%, which was significantly higher (p < 0.05) than that of control group (78.1 ± 19.2%) and C100 group (107.3 ± 28.2%). The uptake of CpG ODNs by haemocytes and the possible mechanism of CpG ODNs to active the immune response were investigated by using the laser scanning confocal microscope. CpG ODNs (labeled with 5'-end-FAM) could be internalized by the haemocytes after incubation of 20 min, with strong signals detected at the cell membrane and in the cytoplasm. In the cytoplasm, most of the CpG ODNs were localized in lysosome, and some of them escaped from the lysosomal compartments and aggregated around the nuclear. The results clearly demonstrated that CpG ODNs could be internalized directly by crab haemocytes and mostly located in the late endosome. The enhancements of immuno-protection efficiency and growth rate from CpG ODNs as supplements in diets might depend on the uptaking and locating processes, and they could be used as a potential immunostimulant for the crab aquaculture.

Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial.

BACKGROUND: In north India, vitamin A deficiency (retinol <0·70 µmol/L) is common in pre-school children and 2-3% die at ages 1·0-6·0 years. We aimed to assess whether periodic vitamin A supplementation could reduce this mortality. METHODS: Participants in this cluster-randomised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks (clusters) were cluster-randomly allocated in Oxford, UK, between 6-monthly vitamin A (retinol capsule of 200,000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of retinol effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial vitamin A to sample blood (for retinol assay, technically reliable only after mid-study), examine eyes, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100,000 visits, 25,000 deaths at ages 1·0-6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. FINDINGS: Estimated compliance with 6-monthly retinol supplements was 86%. Among 2581 versus 2584 children surveyed during the second half of the study, mean plasma retinol was one-sixth higher (0·72 [SE 0·01] vs 0·62 [0·01] µmol/L, increase 0·10 [SE 0·01] µmol/L) and the prevalence of severe deficiency was halved (retinol <0·35 µmol/L 6%vs 13%, decrease 7% [SE 1%]), as was that of Bitot's spots (1·4%vs 3·5%, decrease 2·1% [SE 0·7%]). Comparing the 36 retinol-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0-6·0 years during the 5-year study were 3·01 retinol versus 3·15 control (absolute reduction 0·14 [SE 0·11], mortality ratio 0·96, 95% CI 0·89-1·03, p=0·22), suggesting absolute risks of death between ages 1·0 and 6·0 years of approximately 2·5% retinol versus 2·6% control. No specific cause of death was significantly affected. INTERPRETATION: DEVTA contradicts the expectation from other trials that vitamin A supplementation would reduce child mortality by 20-30%, but cannot rule out some more modest effect. Meta-analysis of DEVTA plus eight previous randomised trials of supplementation (in various different populations) yielded a weighted average mortality reduction of 11% (95% CI 5-16, p=0·00015), reliably contradicting the hypothesis of no effect. FUNDING: UK Medical Research Council, USAID, World Bank (vitamin A donated by Roche).

DHEA and cognition in HIV-positive patients with non-major depression.

BACKGROUND: Dihydroepiandrosterone (DHEA) has been investigated for its potential role in improving cognition in a number of patient populations. Treatment options are limited for HIV-associated neurocognitive disorders. OBJECTIVE: The authors tested the effect of DHEA administration on the cognitive functioning of HIV-positive subjects with non-major depression. METHOD: The neuropsychological testing data for 60 HIV-positive patients enrolled in a clinical trial for non-major depression were analyzed to determine if DHEA-treated patients demonstrated improved cognitive functioning versus placebo. RESULTS: At baseline, 80% of the sample met criteria for asymptomatic cognitive impairment. No benefit in cognitive performance was found on 16 of 17 neuropsychological measures evaluated. One measure showed a modest benefit for placebo-treated patients over DHEA. CONCLUSION: DHEA treatment was not associated with improved cognitive performance in HIV-positive patients with non-major depression.

Quantitative determination of pidotimod in human plasma by liquid chromatography tandem mass spectrometry: application to a bioequivalence study.

A highly sensitive and simple LC-MS/MS method after one-step protein precipitation was developed and validated for determination of pidotimod (CAS 121808-62-6) in human plasma using dextrophan (CAS 125-73-5) as internal standard (IS). Pidotimod and IS were separated on a YMC-ODS-AQ C18 column using 0.5% formic acid and methanol as a mobile phase at a flow rate of 0.3 mL/min. Detection was performed on positive ion mode of the transitions at 245.0→134.0 for pidotimod and 258.1→157.0 for IS by selected reaction monitoring (SRM). The assay exhibited a linear range of 0.05-10.0 µg/mL. The lower limit of quantification were 0.05 µg/mL. Validation results indicated that the accuracy as determined from quality control samples was in the range of - 4.00-6.48%. Intra-day and inter-day precision was ≤ 8.35% and ≤ 8.00%, respectively. The developed method was successfully applied to a bioequivalence study in 20 healthy Chinese volunteers following a single oral dose of 800 mg pidotimod. The simple, inexpensive protein precipitation and high-throughput method makes it a suitable and valuable tool in the investigation of the clinical pharmacokinetics and bioequivalence.

The sustained influence of short term exposure to a proprietary extract of North American ginseng on the hemopoietic cells of the bone marrow, spleen and blood of adult and juvenile mice.

This study assessed the influences of CVT-E002, a proprietary extract of North American ginseng, Panax quinquefolius (Afexa Life Sciences, Inc., Edmonton, AB, Canada), in vivo, on murine hemopoietic and immune cells when administered as a dietary additive. The extract was given daily to young, adult mice for a period of 4 weeks, immediately following which one group was euthanized and the hemopoietic and immune cells of their bone marrow, spleen and blood were assayed for CVT-E002-mediated alterations in any of five cell lineages (lymphocytes, nucleated erythroid cells, granulocytes, immature granuloid precursors and monocytes). Another group of these mice was left for a subsequent 8 weeks on control diet, following which the same organs and cell lineages were analysed. In another study, juvenile mice immediately upon weaning (age: 4 weeks), were subjected to the above protocol, and their organs/cell lineages assayed. The results revealed that CVT-E002 had a long-lasting, positive quantitative effect on the lymphocytes and monocytes, regardless of age at commencement of daily, dietary CVT-E002. CVT-E002 may therefore have a prophylactic disease defense, immunostimulatory role, or potentially, even a therapeutic role.

Dietary astaxanthin enhances immune response in dogs.

No information is available on the possible role of astaxanthin on immune response in domestic canine. Female Beagle dogs (9-10 mo old; 8.2 ± 0.2 kg body weight) were fed 0, 10, 20 or 40 mg astaxanthin daily and blood sampled on wk 0, 6, 12, and 16 for assessing the following: lymphoproliferation, leukocyte subpopulations, natural killer (NK) cell cytotoxicity, and concentrations of blood astaxanthin, IgG, IgM and acute phase proteins. Delayed-type hypersensitivity (DTH) response was assessed on wk 0, 12 and 16. Plasma astaxanthin increased dose-dependently and reached maximum concentrations on wk 6. Dietary astaxanthin enhanced DTH response to vaccine, concanavalin A-induced lymphocyte proliferation (with the 20mg dose at wk 12) and NK cell cytotoxic activity. In addition, dietary astaxanthin increased concentrations of IgG and IgM, and B cell population. Plasma concentrations of C reactive protein were lower in astaxanthin-fed dogs. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune response and reduced DNA damage and inflammation in dogs.

Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment.

AIM: There is little evidence that dehydroepiandrosterone (DHEA) has beneficial effects on physical and psychological functions in older women. We investigated the effect of DHEA supplementation on cognitive function and ADL in older women with cognitive impairment. METHODS: A total of 27 women aged 65-90 years (mean ± standard deviation, 83 ± 6) with mild to moderate cognitive impairment (Mini-Mental State Examination, MMSE; 10-28/30 points), receiving long-term care at a facility in Japan were enrolled. Twelve women were assigned to receive DHEA 25 mg/day p.o. for 6 months. The control group (n = 15) matched for age and cognitive function was followed without hormone replacement. Cognitive function was assessed by MMSE and Hasegawa Dementia Scale-Revised (HDS-R), and basic activities of daily living (ADL) by Barthel Index at baseline, 3 and 6 months. Plasma hormone levels including testosterone, DHEA, DHEA-sulfate and estradiol were also followed up. RESULTS: After 6 months, DHEA treatment significantly increased plasma testosterone, DHEA and DHEA-sulfate levels by 2-3-fold but not estradiol level compared to baseline. DHEA administration increased cognitive scores and maintained basic ADL score, while cognition and basic ADL deteriorated in the control group (6-month change in DHEA group vs control group; MMSE, +0.6 ± 3.2 vs -2.1 ± 2.2, P < 0.05; HDS-R, +2.8 ± 2.8 vs -0.3 ± 4.1, P < 0.05; Barthel Index, +3.7 ± 7.1 vs -2.7 ± 4.6, P = 0.05). Among the cognitive domains, DHEA treatment improved verbal fluency (P < 0.05). CONCLUSION: DHEA supplementation in older women with cognitive impairment may have beneficial effects on cognitive function and ADL.

A randomized trial of oral DHEA treatment for sexual function, well-being, and menopausal symptoms in postmenopausal women with low libido.

INTRODUCTION: Dehydroepiandrosterone (DHEA) and its sulfate DHEAS, which are the most abundant steroids in women, decline with age. We have shown association between low sexual function and low circulating DHEAS levels in women. AIM: The aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function. METHODS: Ninety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week randomized, double-blind, placebo controlled trial and received either DHEA 50 mg or placebo (PL) daily. MAIN OUTCOME MEASURES: Efficacy was assessed through 26 weeks. The main outcome measures were the change in total satisfying sexual events (SSE) and the change in the Sabbatsberg Sexual Self-Rating Scale (SSS) total score. Secondary measures were the Psychological General Well-Being Questionnaire (PGWB), and the Menopause-Specific Quality of Life Questionnaire (MENQOL). Hormonal levels, adverse events (AEs), serious adverse events (SAEs) and clinical labs were evaluated over 52 weeks. RESULTS: Eighty-five participants (91%) were included in the 26-week efficacy analysis. There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS, PGWB, and MENQOL change scores. Overall AE reports and number of withdrawals as a result of AEs were similar in both groups; however more women in the DHEA group experienced androgenic effects of acne and increased hair growth. CONCLUSIONS: In this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA resulted in no significant improvements in sexual function over PL therapy over 26 weeks.

Sphingosine 1-phosphate enhances Fc gamma receptor-mediated neutrophil activation and recruitment under flow conditions.

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that is released by platelets and endothelial cells and has been implicated in diverse biological functions. We hypothesized that S1P may influence immune complex-mediated polymorphonuclear neutrophil activation. Using flow cytometry and fluorescence spectrometry, we found that exogenous addition of S1P led to an enhanced polymorphonuclear neutrophil Fcgamma receptor-mediated rise in intracellular Ca(2+) and reactive oxygen species generation in a pertussis toxin-independent manner, while having only a small effect by itself. Thus, S1P amplifies a positive feedback loop where Fcgamma receptor-mediated rises in Ca(2+) and reactive oxygen species are interdependent, with reactive oxygen species acting to increase tyrosine phosphorylation and activity of upstream signaling intermediates. S1P augmentation of Fcgamma receptor signaling translates to downstream functional consequences, including shape change and recruitment to endothelial surfaces coated with suboptimal levels of immune complexes. Taken together, S1P from activated platelets or endothelial cells may serve to amplify leukocyte recruitment and tissue injury at sites of immune complex deposition in vasculitis.

Oxylipins from Dracontium loretense.

Four novel oxylipins (1-4) were isolated from the n-butanol extract of the corms of Dracontium loretense. Their structures were assigned by 1D and 2D NMR analyses and electrospray ionization multistage ion trap mass spectrometry (ESI-ITMS(n)) data. Relative configurations were assigned on the basis of combined analysis of homonuclear and heteronuclear (2,3)J couplings, along with ROE data. Oxylipin 2 exhibited an immunostimulatory effect on human PBMC proliferation.

Melatonin, as an adjuvant-like agent, enhances platelet responsiveness.

Melatonin exerts immunomodulatory actions that enhance the magnitude and quality of immune responses specific for certain antigens; this has raised the possibility of using melatonin to design novel vaccine adjuvant systems. The present study investigated the effect of subcutaneous slow-release melatonin implants and subcutaneous melatonin injections on the responsiveness of circulating platelets in sheep after vaccination against Dichelobacter nodosus (A1 and C serotypes), the bacterium that causes ovine footrot, a major cause of lameness in sheep. The experiments were carried out in sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by radioimmunoassay, sheep platelet aggregation was monitored using an aggregometer and Ca2+ mobilization was determined by spectrofluorimetry using fura-2. Administration of melatonin either by implants or subcutaneous injections increased plasma melatonin concentrations, an effect that was found to be greater and more sustained when melatonin was administered via implants. Vaccination per se, as well as melatonin, increased the percentage and rate of platelet aggregation and reduced the lag-time in response to the physiological agonist thrombin, an effect that was found to be significantly greater when melatonin was administered to vaccinated animals. Melatonin enhanced thrombin-evoked Ca2+ release and entry and further increased Ca2+ mobilization observed in platelets from vaccinated sheep. These observations suggest that the use of melatonin, as a novel adjuvant, induces beneficial effects on platelet function and haemostasis, and opens new perspectives for therapeutic manipulation of immune responses to vaccination.

Hormonal responses to marathon running in non-elite athletes.

BACKGROUND: Exercise is known to be a powerful stimulus for the endocrine system. The hormonal response to exercise is dependent on several factors including the intensity, duration, mode of exercise (endurance versus resistance), and training status of the subject. The aim of the present study was to determine the steroid hormonal response (immediately after a race and 1 week later) to endurance exercise under the real conditions of the classic Athens marathon in a group of well-trained, middle-aged, non-elite athletes. METHODS: Blood samples were drawn 1 week before the race, directly after completion of the race, and 1 week later. RESULTS: Serum cortisol and prolactin showed distinct rises 1 h after the race and returned to baseline 1 week later. Androstenedione and dehydroepiandrosterone sulphate did not show any changes. Total testosterone as well as free testosterone dropped significantly 1 h after the race but returned to baseline 1 week later. CONCLUSION: In this particular group of non-elite, middle-aged marathon runners, the race resulted in an acute increase in serum cortisol and prolactin levels and in a concomitant decline in testosterone level. The aforementioned changes returned to baseline 1 week later.

Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract.

The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.9 mg) was evaluated in a pharmacokinetic study in humans and the possible effects on the immunological system were measured. Alkamides were found to be rapidly absorbed and measurable in plasma 10 min after administration of 0.21 and 0.9 mg lozenges and remained detectable for 3h for the 0.21 mg lozenges and for more then 3h for the 0.9 mg lozenges; 0.07 mg lozenges were measurable 20 min after administration and remained detectable for only 2h after the administration. A significant dose-independent down-regulation of the pro-inflammatory cytokines IL-12p70, IL-8, IL-6, IL-10 and TNF was observed 24h after oral administration. The results of non-compartmental pharmacokinetic analysis revealed that a C(max) of (0.65+/-0.41 ng/ml) was reached at 32 min with the 0.07 mg lozenges, (1.00+/-0.21ng/ml) at 25 min with the 0.21 mg lozenges and (8.88+/-5.89 ng/ml) at 19 with the 0.9mg lozenges. As evidenced by the dose-exposure relationship, no significant departure from dose proportionality was observed, indicating linearity in pharmacokinetics. To get a further insight in pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides a compartmental population pharmacokinetic model was developed applying mixed effect modelling procedure. The results demonstrate that within the dose range studied pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides are linear and that absorption is very rapid (t(1/2)=6 min) with apparently no lag time, thus indicating the possibility that a fraction of the drug is absorbed through the oral mucosa.

Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi.

Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In a previous study, we reported that administration of DHEA significantly decreased the numbers of blood parasites in Trypanosoma cruzi experimental infection. The present study was undertaken to determine the effectiveness of DHEA in reducing the severity of acute phase T. cruzi infection of male and female Wistar rats. Animals were treated subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined in the sera of uninfected and infected animals. DHEA treatment augments NO production for both sexes after in vitro LPS treatment for uninfected animals. Infection triggered enhanced NO levels although not significant. IL-2 and IFN-gamma were detectable in higher concentrations in treated and infected rats of both genders when compared to untreated controls. These data suggest that DHEA may have a potent immunoregulatory function that can affect the course of T. cruzi infection.

Treatment with dehydroepiandrosterone in vivo and in vitro inhibits reproduction, growth and viability of Taenia crassiceps metacestodes.

The aim of this work was to explore the effect of dehydroepiandrosterone (DHEA) on the establishment, growth and reproduction of the metacestode stage of the tapeworm Taenia crassiceps, both in vivo and in vitro. Administration of DHEA prior to infection in mice of both sexes reduced the parasite load by 50% compared with untreated mice. This protective effect was not associated with the immune response, since there was no effect of DHEA treatment on mRNA levels of IL-2, IFN-gamma, IL-4 or IL-10. DHEA treatment of infected mice increased androgen receptor expression in splenocytes of both sexes. Moreover, in vitro treatment of T. crassiceps with DHEA reduced reproduction, motility and viability in a dose- and time-dependent fashion. Results indicate that DHEA has strong negative direct modulatory effects on murine cysticercosis. We suggest the use of hormonal-analogues for protective purposes as a therapeutic approach to prevent murine cysticercosis.