CagA-positive Helicobacter pylori infection and reduced sperm motility, vitality, and normal morphology.

Helicobacter pylori (HP) infection, particularly when caused by strains expressing CagA, may be considered a concomitant cause of male and female reduced fertility. This study explored, in 87 HP-infected males, the relationship between infection by CagA-positive HP strains and sperm parameters. HP infection and CagA status were determined by ELISA and Western blotting; semen analysis was performed following WHO guidelines. The amino acid sequence of human enzymes involved in glycolysis and oxidative metabolism were "blasted" with peptides expressed by HP J99. Thirty-seven patients (42.5%) were seropositive for CagA. Sperm motility (18% versus 32%; P < 0.01), sperm vitality (35% versus 48%; P < 0.01) and the percentage of sperm with normal forms (18% versus 22%; P < 0.05) in the CagA-positive group were significantly reduced versus those in the CagA-negative group. All the considered enzymes showed partial linear homology with HP peptides, but four enzymes aligned with four different segments of the same cag island protein. We hypothesize a relationship between infection by strains expressing CagA and decreased sperm quality. Potentially increased systemic levels of inflammatory cytokines that occur in infection by CagA-positive strains and autoimmune phenomena that involve molecular mimicry could explain the pathogenetic mechanism of alterations observed.

The association of body composition and sex hormones with quantitative ultrasound parameters at the calcaneus and phalanxes in elderly women.

We investigated the associations of body composition and sex hormones with quantitative ultrasound (QUS) parameters carried out at different skeletal sites. In 897 postmenopausal women (64.1 ± 6.6 years) we measured QUS at the calcaneus (stiffness) by Achilles-GE and at phalanxes (amplitude-dependent speed of sound [AD-SOS], bone transmission time [BTT], and ultrasound bone profile index [UBPI]) by Bone Profiler-IGEA. In all subjects we measured fat mass (FM), lean mass (LM), android fat, and gynoid fat by DXA. In all subjects we also assessed serum testosterone (T), estradiol (E(2)), sex-hormone binding globulin, free estrogen index (FEI), free androgen index, 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase (B-ALP), and type I collagen ß carboxy telopeptide. Both E(2) and FEI showed weak but significant correlations with stiffness and QUS parameters at phalanxes. No significant relationships were found between T and QUS. BMI and LM were positively correlated with stiffness (r = 0.14 and r = 0.17, respectively), whereas BMI and FM showed negative correlations with AD-SOS, BTT, and UBPI. 25OHD showed positive relationships with stiffness and QUS at phalanxes. In multivariate models LM and age were associated with stiffness whereas E(2) and age were significant predictors of BTT. AD-SOS was negatively associated with FM, B-ALP, and age but positively with E(2) and 25OHD. In postmenopausal women QUS parameters at the calcaneus and at phalanxes are significantly, but diversely, associated with body composition, sex hormones, 25OHD, and bone turnover markers.

The effects on lipid serum levels of a 2-year adjuvant treatment with exemestane after tamoxifen in postmenopausal women with early breast cancer.

BACKGROUND: The third-generation aromatase inhibitor exemestane represents a new development in the treatment of estrogen-positive breast cancer. The aim of this study was to evaluate the effects on lipid profile and body composition of the shift from tamoxifen to exemestane. METHODS: After 2-3 years of tamoxifen adjuvant treatment, 68 postmenopausal women were randomly assigned to either continue tamoxifen 20 mg/day (n = 35) or to switch to exemestane 25 mg/day (n = 33). RESULTS: No significant changes in lipid profile were found in patients continuing on tamoxifen. In the exemestane group, serum HDL-cholesterol (HDL-C) and triglycerides (TG) decreased significantly (p < 0.01) and serum LDL-cholesterol (LDL-C) increased significantly (p < 0.05) with respect to baseline. The difference between the two groups was significant. Moreover, in the exemestane group, fat mass (FM) and fat-free mass (FFM) showed an opposite trend, which determined a progressive and significant increase in the FFM/FM ratio. CONCLUSION: This study shows that the choice of first-line treatment or adjuvant therapy for breast cancer should also take the individual lipid and body composition profile into account.

Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis.

The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.

A new serum assay to measure N-terminal fragment of telopeptide of type I collagen in patients with renal osteodystrophy.

BACKGROUND: Up until now, there was little known about the use of bone resorption markers in the assessment of bone status in patients with chronic renal failure (CRF). The present study evaluated the ability of a new immunoassay for N-terminal telopeptide of type I collagen to assess bone turnover in a group of hemodialyzed patients. METHODS: The following parameters were measured in a fasting blood sample from 111 patients on maintenance hemodialysis for at least 2 years and in 120 healthy subjects: calcium, phosphorus, magnesium, BALP, PTH, and N-terminal telopeptide of type I collagen (NTx-ELISA, OSTEOMARK NTx Siero-Ostex International). RESULTS: Serum PTH, BALP, and NTx were significantly higher (P<0.001) in hemodialyzed (HD) patients than in healthy subjects. In HD patients, PTH was correlated to BALP and NTx (r=0.40 and 0.55, respectively). When combining PTH and BALP serum levels, 17 patients showed high turnover (HT) and 65 were found to have a normal to low turnover (N-LT). In HT patients, serum NTx and dialytic age were significantly (P<0.01) higher than in N-LT patients. Moreover, even after adjusting for age, body mass index, dialytic age, and calcium-vitamin D treatment, serum NTx discriminated between HT and N-LT with a sensitivity of 97.6% and a specificity of 90.9%. CONCLUSION: Although bone biopsy remains the reference method for the diagnosis of renal osteodystrophy, the combined use of markers of bone resorption and bone formation could improve the clinical management of renal bone diseases.

Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study.

Although several studies have reported a lower risk of osteoporotic fracture in hypercholesterolemic patients treated with statins, so far longitudinal studies on the effects of statins on bone are lacking. The aim of the present study was to evaluate bone mineral density (BMD) and bone turnover changes induced by 1-year simvastatin treatment on postmenopausal women. Thirty consecutive postmenopausal hypercholesterolemic women (61.2 +/- 4.9 years) were treated for 12 months with 40 mg/day simvastatin and 30 normocholesterolemic age-matched postmenopausal women provided control data. In all subjects, at baseline and at 3-month intervals, serum lipids, calcium, phosphate, total and bone alkaline phosphatase (Bone-ALP), and carboxy-terminal fragment of type I collagen (CTx) were measured in a fasting blood sample. At baseline and after 6 and 12 months BMD was measured at lumbar spine (BMD-LS) and at femur (BMD-Ftot) and at femoral neck (BMD-Fn) by DXA. In the simvastatin-treated group Bone-ALP showed a significant increase (P < 0.05) with respect to baseline from the sixth month, whereas serum CTx showed a weak and nonsignificant increase over the study period. In treated women BMD-LS, BMD-Fn, and BMD-Ftot increased respectively by 1.1, 0.9, and 0.4% at Month 6; and by 2.8, 1.0, and 0.8% at Month 12. In controls BMD-LS, BMD-Fn, and BMD-Ftot at the end of the study period decreased by 1.6, 1.4, and 1.2%, respectively. The difference between controls and simvastatin-treated patients was significant (P < 0.05) for both BMD-LS and BMD-Fn only at Month 12. In conclusion our results, although obtained from a small sample of postmenopausal hypercholesterolemic women, suggest a probable positive effect of simvastatin on bone formation and BMD.

Changes in serum HDL and LDL cholesterol in patients with Paget's bone disease treated with pamidronate.

Amino bisphosphonates represent one of the most important advances in the management of Paget's and other metabolic bone diseases. Although their mechanism of action has not yet been completely clarified, they seem to inhibit the mevalonate pathway and so they could interfere with cholesterol synthesis. The present study aimed to evaluate cholesterol and lipoprotein serum levels in patients with Paget's bone disease treated with intravenous pamidronate. The study included 20 consecutive patients (mean age, 67.6 +/- 11.0 years) with Paget's bone disease for at least 1 year, who needed intravenous amino bisphosphonate treatment; 12 patients with inactive Paget's bone disease served as controls. The patients with active Paget's bone disease underwent three cycles (every 3 months) of treatment with 60 mg of intravenous pamidronate. Controls were given a saline infusion following the same administration schedule. In all subjects total alkaline phosphatase (total ALP), bone alkaline phosphatase (bone ALP), total cholesterol (TC), tryglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively) were measured before infusions (pamidronate or saline) at baseline and at 3-month intervals up to 9 months. In the control group no significant changes were observed through the study period for any of the biochemical parameters. In the pamidronate-treated patients, both bone ALP and total ALP significantly fell at the end of the study. In patients with active treatment, at the end of the study period HDL-C significantly (P < 0.05) increased by 10.3%, whereas LDL-C significantly (P < 0.05) decreased by 5.5%. In these patients TC showed a negative trend without reaching statistical significance, whereas the HDL-C/LDL-C ratio rose 16.2% above the basal value and TC/HDL-C decreased by 12.5%. In conclusion, pamidronate given intravenously seems to be able to induce a prolonged shifting in circulating cholesterol from the LDL-C to the HDL-C from associated with a weak decrease in total cholesterol, thus producing a possible improvement in the atherosclerotic risk index.

Bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases.

We have investigated the clinical utility of a new quantitative two-site radioimmunometric assay specific for bone alkaline phosphatase (B-ALP) in 219 healthy control subjects and in 264 patients with various metabolic bone diseases. B-ALP was compared with total alkaline phosphatase (T-ALP) and with osteocalcin (BGP). B-ALP increased linearly with age in both sexes. In postmenopausal normal women B-ALP increased by 82% compared with premenopausal normal women, whereas the differences between pre- and postmenopausal women for T-ALP and BGP were 18% and 30% respectively. As assessed by Z-score, the highest values of B-ALP were found in patients with Paget's disease of bone, bone metastases or hyperparathyroidism and in patients on maintenance haemodialysis. In osteoporotic patients, B-ALP< but not T-ALP, showed a slight but significant (P < 0.05) difference compared with normal women. On the basis of bone turnover, osteoporotic patients were divided into two groups: high turnover and low turnover; B-ALP, like BGP, was significantly (P < 0.01) higher in patients with high turnover. In conclusion, B-ALP, measured by this new method, can be considered a sensitive marker of bone turnover and could be especially useful in identifying women at risk of developing osteoporosis.

[The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis]. / Efficacia e tollerabilità della glucosamina solfato nel trattamento della gonartrosi.

This study was performed to evaluate the therapeutic efficacy and tolerability of glucosamine sulfate in patients with gonarthritis. During the 12-month study period, the signs and symptoms of the disease were evaluated, as well as the dosage of the urinary pyridinoline. In this trial, we demonstrated that glucosamine sulfate has a chondroprotective activity, which was significant after the first 3 months of therapy. Moreover, this study showed that the side effects due to glucosamine sulfate were mild to moderate and did not require discontinuation of the drug.

Tolerability of nabumetone: a pilot in vitro study showing absence of injury to articular cartilage.

Nabumetone, a compound of the naphthylalkanone class, has shown considerable anti-inflammatory, analgesic and antipyretic effects, together with high systemic and organ-specific tolerability. Its reputation for tolerability has been increased by an in-vitro study evaluating the mature collagen metabolism's markers under nabumetone treatment, which shows that, nabumetone does not interfere with collagen synthesis. Therefore, unlike some nonsteroidal anti-inflammatory drugs, nabumetone might not be injurious to articular cartilage. This feature makes nabumetone even safer for long-term treatment of rheumatic and orthopaedic conditions.

[Behavior of plasma and urinary cAMP after intravenous fructose load]. / Comportamento dell'AMPc plasmatico e urinario dopo carico endovenoso di fruttoso.

Increased excretion of uric acid and cAMP has been observed in many pathological conditions in man, but interrelation between behaviour of uric acid and cAMP is not well known. To investigate these aspects of purine metabolism the authors have studied behaviour of plasma and urinary cAMP in 8 subjects after intravenous rapid load of fructose (0.5 g/Kg b.w.) compared with the uric acid one. The results have shown that urinary excretion of cAMP after load of fructose is increased, but levels of plasma cAMP remain unchanged. These data confirm consensual relation between urinary uric acid and cAMP excretion, but the exact mechanism of this relation remains unexplained.

[Behavior of urinary excretion of cyclic AMP in post-menopausal osteoporosis during therapy with salmon calcitonin]. / Comportamento dell'escrezione urinaria di AMP ciclico nella osteoporosi post-menopausale in corso di terapia con calcitonina di salmone.

Salmon calcitonin has been administered at a dose of 100 U.M.R.C. for 6 months in 10 patients suffering from post-menopausal osteoporosis. During treatment, calcium plasma levels fluctuated but tended to fall, while urinary excretion of cyclic AMP rose, this pointing to an enhancement of parathyroid function. After 6 months an increase in intestinal calcium absorption and a decrease in bone turnover were also observed, the bone mineral content evaluated by bone densitometry showed a slight quantitative increase but proved to be substantially unchanged. Salmon calcitonin thus proved capable of interfering with bone turnover by reducing the bone resorption. By fostering an increase in parathyroid hormone production, it also made it possible to exploit that anabolic effect which, in low doses, the parathormone exerts on the bone tissue.

[Metabolic changes induced with salmon calcitonin in post-menopausal osteoporosis]. / Modificazioni metaboliche indotte dalla calcitonina di salmone nella osteoporosi post-menopausale.

10 patients suffering from post-menopausal osteoporosis were subjected to venous infusion of salmon calcitonine at a dose of 100 U.M.R.C. Essential inital biochemical data were hypocalcaemia associated with plasma increase in AMPc and, in the late phase, an increase in urinary excretion of phosphate and AMPc. In addition to conserving its physiological properties in osteoporotic disease also, the hormone is thus able to provoke a secondary secretion of parathormone. The use of CT in the treatment of post-menopausal osteoporosis is therefore recommended not only because of its evident action on bone reabsorption processes, which usually predominate in this dysmetabolic disease of the skeleton, but also in the indirect secretion of parathyroid hormone which is capable of positively affecting synthesis of 1-25 (OH)2 D3 and intestinal calcic absorption.