| 1. |
- Bobjer, Johannes, et al.
(author)
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Serum chemerin levels are negatively associated with male fertility and reproductive hormones
- 2018
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 33:12, s. 2168-2174
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Journal article (peer-reviewed)abstract
- STUDY QUESTION: Are chemerin levels different in subfertile men compared to men from the general population, and how does chemerin relate to reproductive hormonal status? SUMMARY ANSWER: Chemerin is negatively associated to LH, SHBG and estradiol and lower levels of chemerin are detected among subfertile men compared to controls. WHAT IS KNOWN ALREADY: Adipokines have pleiotropic effects on tissue homeostasis and have been shown to affect both sex steroid production and action. Among adipokines the newly characterized chemokine chemerin is suggested to influence testosterone production in males, but whether serum levels associate with testosterone or male subfertility has not yet been reported. STUDY DESIGN, SIZE, DURATION: Case control study comprising a consecutive group of men from infertile couples referred to Reproductive Medicine Centre at Skane University Hospital from 2006 through 2012, and age-matched controls. Participants were enrolled in years 2011-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Males from infertile couples (n = 180) aged 18-50 years with sperm concentration <20 × 106/ml and age-matched controls (n = 139) from the general population were enrolled. Serum concentrations of total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and sex-hormone binding globuline (SHBG) as well as the adipokines chemerin, adiponectin and leptin were measured. Anthropometrics and biochemical parameters of glucose and lipid metabolism were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Chemerin levels were lower in subfertile men compared to controls (mean diff. 7.1 ng/ml; 95% CI, 3.7; 11 ng/ml; P < 0.001) even after adjustment for BMI. After adjustment for age, BMI, smoking, leptin and adiponectin, chemerin associated negatively with LH (ß = -4.2; P = 0.02), E2 (ß = -10; P = 0.004) and SHBG (ß = -7.4, P = 0.003). Men with elevated LH levels had lower chemerin levels compared to those with LH levels within the normal range (mean diff. 4.8 ng/ml; 95% CI, 0.16; 9.4 ng/ml; P = 0.04). LIMITATIONS, REASONS FOR CAUTION: Single sample blood test with immunoassays for determination of hormone levels. Heterogeneous group of subfertile subjects. WIDER IMPLICATIONS OF THE FINDINGS: Even though chemerin has been positively associated with BMI, inverse association with subfertility suggests that it is independently linked to reproductive function, a hypothesis that warrants further assessment. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from EU Interreg V (ReproUnion) program as well as Swedish Governmental Fund for Clinical Research. The authors have no conflicts of interest.
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| 2. |
- Faux, Noel G, et al.
(author)
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PBT2 Rapidly Improves Cognition in Alzheimer's Disease : Additional Phase II Analyses
- 2010
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:2, s. 509-516
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Journal article (peer-reviewed)abstract
- PBT2 is a copper/zinc ionophore that rapidly restores cognition in mouse models of Alzheimer's disease (AD). A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta_{42}, and significantly improved executive function on a Neuro-psychological Test Battery (NTB) within 12 weeks of treatment in patients with AD. In the post-hoc analysis reported here, the cognitive, blood marker, and CSF neurochemistry outcomes from the trial were subjected to further analysis. Ranking the responses to treatment after 12 weeks with placebo, PBT2 50 mg, and PBT2 250 mg revealed that the proportions of patients showing improvement on NTB Composite or Executive Factor z-scores were significantly greater in the PBT2 250 mg group than in the placebo group. Receiver-operator characteristic analyses revealed that the probability of an improver at any level coming from the PBT2 250 mg group was significantly greater, compared to placebo, for Composite z-scores (Area Under the Curve [AUC] =0.76, p=0.0007), Executive Factor z-scores (AUC =0.93, p=1.3 x 10;{-9}), and near-significant for the ADAS-cog (AUC =0.72, p=0.056). There were no correlations between changes in CSF amyloid-beta or tau species and cognitive changes. These findings further encourage larger-scale testing of PBT2 for AD.
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| 3. |
- Strozyk, Dorothea, et al.
(author)
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Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid.
- 2009
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:7, s. 1069-77
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Journal article (peer-reviewed)abstract
- Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Abeta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Abeta and biological metals in CSF. We assayed CSF copper, zinc, other metals and Abeta42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF Abeta42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Abeta42. In vitro, the degradation of synthetic Abeta substrate added to CSF was markedly accelerated by low levels (2microM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta degradation is normally promoted by physiological copper and zinc concentrations.
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| 4. |
- Tsatsanis, Christos, et al.
(author)
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Serum miR-155 as a potential biomarker of male fertility.
- 2015
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:4, s. 853-860
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Journal article (peer-reviewed)abstract
- Are serum levels of micro-RNAs miR-155 and miR-146a associated with male fertility, low-grade systemic inflammation (LGSI) and androgens?
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