The effects in vitro of TNF-α and its antagonist 'etanercept' on ejaculated human sperm.

Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500ng mL-1) and etanercept (from 800µg mL-1 to 2000µg mL-1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200µg mL-1, etanercept can block, in a significant way, the toxic effects of TNF-α (500ng mL-1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.

Effect of Mud-Bath Therapy on Serum Biomarkers in Patients with Knee Osteoarthritis: Results from a Randomized Controlled Trial.

BACKGROUND: Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response. OBJECTIVES: To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. METHODS: The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA. RESULTS: At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in either group, while a significant increase (P < 0.001) in CTX-II serum levels was observed in the mud-bath group after the treatment. CONCLUSIONS: A cycle of mud-bath therapy added to the usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed a significant increase of CTX-II only, perhaps due to an increase of cartilage turnover induced by thermal stress.

Raloxifene protects cultured human chondrocytes from IL-1ß induced damage: a biochemical and morphological study.

It is well known that estrogens are implicated in the pathogenesis of osteoarthritis. Raloxifene is a selective estrogen receptor modulator used in the treatment of osteoporosis, though little is known about the possible effects of raloxifene on cartilage metabolism. The aim of our study was to evaluate the possible in vitro effects of raloxifene in human osteoarthritis chondrocytes cultivated in the presence or absence of Interleukin-1 beta (IL-1ß) (5 ng/ml). The effects of 0.1 µM and 1 µM of raloxifene in the culture medium were assessed using an immuno-enzymatic method for proteoglycans and metalloproteinase-3 (MMP-3), and the Griess method for nitrite. Gene expression of inducible Nitric Oxide Synthase (iNOS) was detected by real-time PCR. A morphological analysis was performed by transmission electron microscopy (TEM). Cell viability was significantly (P<0.01) reduced by the IL-1ß, and restored to basal levels by raloxifene at both of the concentrations used. The presence of IL-1 ß led to a significant decrease (P<0.01) in proteoglycan levels as well as a significant increase of MMP-3 and NO (P<0.01). When the cells were co-incubated with IL-1ß and raloxifene, a significant and dose-dependent increase in proteoglycans and a reduction of MMP-3 and nitric oxide (NO) were detected. iNOS was noticeably expressed in IL-1ß stimulated chondrocytes, while raloxifene decreased in a very significant manner the gene expression of iNOS at both of the concentrations used. The results of the biochemical evaluation were confirmed by TEM. Our data suggest that raloxifene may have a potential chondroprotective role in osteoarthritis.