Clusterin silencing restores myoblasts viability and down modulates the inflammatory process in osteoporotic disease.

BACKGROUND: Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. METHODS: Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. RESULTS: We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p < 0.001). CLU treatment of isolated OP and OA myoblasts showed: modulation of proliferation, morphological changes, increase of histone H4 acetylation and induction of myogenin (MYOG) activation in OP myoblast only. In OP condition, functional knockdown of CLU by siRNA restores proliferative myoblasts capability and tissue damage repair, carried out by an evident upregulation of Transglutaminase 2 (TGM2). We also observed downmodulation of CX3CR1 expression with consequent impairing of the inflammatory infiltrate recruitment. CONCLUSIONS: Results obtained suggest a potential role of CLU in OP by influencing myoblasts terminal differentiation, epigenetic regulation of muscle cell differentiation and senescence. Moreover, CLU silencing points out its role in the modulation of tissue damage repair and inflammation, proposing it as a new diagnostic marker for muscle degeneration and a potential target for specific therapeutic intervention in OP related sarcopenia.

Irisin levels correlate with bone mineral density in soccer players.

Irisin, a novel myokine produced in response to physical exercise by skeletal muscle, displays anabolic effect on bone and can improve the bone-loss-induced osteoporosis in hind limb suspended mice. It is well known that muscles positively impact the skeleton and in different sports, including soccer, total body bone mineral density (TB-BMD) is elevated. Therefore, we have investigated the correlation between irisin serum levels and total and bone sub-regional BMD in soccer players never studied before. In this study, Caucasian football players of Bari team have been enrolled. Their sera were collected to measure by ELISA kit irisin levels and by dual-energy X-ray absorptiometry (DEXA) analysis measurements of BMD (g • cm−2) in the whole body and different bone sub-regions (head, arms, legs, ribs, dorsal vertebrae, lumbar vertebrae, pelvis) were performed. The BMC (g) was measured in the whole body. By means of Pearson's (R) and Cohen's (d) coefficient we investigated the linear association between the irisin serum levels and BMD. In soccer players, we have found a positive correlation between irisin and TB-BMD as demonstrated by the values of Pearson and Cohen's (d) coefficient. Furthermore, linear association was detected between irisin and BMD of different bone-site such as right arm, lumbar vertebrae and head. A positive trend was also observed analyzing circulating levels of irisin and bone mineral content as well as total Z-score. In conclusion, we have demonstrated the correlation between irisin and total or bone sub-regional BMD in soccer players for the first time, an additional systemic effect of the "sport-hormone" defined myokine.

Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis.

UNLABELLED: We demonstrated that osteoporosis is associated with a preferential type II muscle fiber atrophy, which correlates with bone mineral density and reduced levels of Akt, a major regulator of muscle mass. In osteoarthritis, muscle atrophy is of lower extent and related to disease duration and severity. INTRODUCTION: Osteoarthritis (OA) and osteoporosis (OP) are associated with loss of muscle bulk and power. In these diseases, morphological studies on muscle tissue are lacking, and the underlying mechanisms of muscle atrophy are not known. The aim of our study was to evaluate the OP- or OA-related muscle atrophy and its correlation with severity of disease. Muscle levels of Akt protein, a component of IGF-1/PI3K/Akt pathway, the main regulator of muscle mass, have been determined. METHODS: We performed muscle biopsy in 15 women with OP and in 15 women with OA (age range, 60-85 years). Muscle fibers were counted, measured, and classified by ATPase reaction. By statistical analysis, fiber-type atrophy was correlated with bone mineral density (BMD) in the OP group and with Harris Hip Score (HHS) and disease duration in the OA group. Akt protein levels were evaluated by Western blot analysis. RESULTS: Our findings revealed in OP a preferential type II fiber atrophy that inversely correlated with patients' BMD. In OA, muscle atrophy was of lower extent, homogeneous among fiber types and related to disease duration and HHS. Moreover, in OP muscle, the Akt level was significantly reduced as compared to OA muscles. CONCLUSIONS: This study shows that in OP, there is a preferential and diffuse type II fiber atrophy, proportional to the degree of bone loss, whereas in OA, muscle atrophy is connected to the functional impairment caused by the disease. A reduction of Akt seems to be one of the mechanisms involved in OP-related muscle atrophy.

The bone anabolic therapy.

Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide [PTH (1­34)], is a drug with a proven anabolic action on the bone, effective in preventing vertebral and non-vertebral fragility fractures. Recent publications have investigated in great detail the TPTD action on the cortical bone, highlighting the increased strength in the critical zone of the hip with high risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In November 2002, TPTD was approved by the FDA for use in post-menopausal women and men with osteoporosis at high risk of fracture and in patients with glucocorticoid-induced osteoporosis and, since then, has been used to treat more than 1 million patients worldwide (J Bone Miner Res 27(12):2429-2437, 2012). The unchanged safety profile and the well-known mechanism of action of this drug have led doctors to explore the use of TPTD in other conditions such as delayed fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports that have resulted from these studies are helping to hypothesize a new perspective on the wider use of this drug, but warrant further clinical investigation to consolidate these results.

Analysis of prognostic factors in COVID-19 hospitalized patients: an Italian single-center case-control study.

OBJECTIVE: COVID-19 clinical presentation ranges from asymptomatic infection to an inflammatory cytokine storm with multi-organ failure and fatal outcomes. The identification of high-risk patients for severe disease is crucial to plan an early treatment and intensive follow-up. We aimed to investigate negative prognostic factors in a group of patients hospitalized for COVID-19. PATIENTS AND METHODS: 181 patients (90 men and 91 women, mean age 66.56 ± 13.53 years) were enrolled. Each patient received a work-up including medical history, clinical examination, arterial blood gas analysis, laboratory blood tests, feasible ventilatory support required during hospital stay, intensive care setting required, duration of illness and length of hospital stay (>or<25 days). For the assessment of the severity of COVID-19, three main indicators were considered: 1) the intensive care unit (ICU) admission 2) the hospitalization length >25 days; 3) the need of non-invasive ventilation (NIV). RESULTS: The independent risk factor associated with the ICU admission were lactic dehydrogenase elevation (p=0.046), C reactive protein elevation (p=0.014) at hospital admission and direct oral anticoagulant home therapy (p=0.048); for hospital length >25 days: early corticosteroid therapy (p=0.035); for NIV treatment: ferritin elevation at hospital admission (p=0.006). CONCLUSIONS: The presence of the above factors may be useful to identify patients at high risk of developing a severe COVID-19 that need an early treatment and intensive follow-up.

Changes in serum levels of TNF-alpha, IL-6, OPG, RANKL and their correlation with radiographic and clinical assessment in fragility fractures and high energy fractures.

Stages of bone turnover during fracture repair can be assessed employing serum markers of osteoblastic and osteoclastic activity, inflammatory cytokines, clinical evaluation and imaging instruments. Our study compare the fracture healing process in fragility fractures and high energy fractures by evaluating serum changes of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), osteoprotegerin (OPG) and receptor activator of the nuclear factor-kB ligand (RANKL) in combination with radiographic (Radiographic Union Scale for Tibial fractures, RUST) and clinical (Lower extremity measure, LEM) assessments. We enrolled 56 patients divided into four corresponding groups: group A with high energy trauma fracture (tibial/femoral shaft); group B with low energy trauma fracture (femoral fractures); healthy (control A) and osteoporotic subjects (control B). Blood samples were collected before surgery (T0) and after 10 weeks (T10). Serum concentrations of IL-6, TNF-alpha, RANKL and OPG were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. Our results show that RANKL values are significantly higher at T10 than at T0 in low energy trauma fractures (group B). OPG is significantly lower in each control group than that of the respective fractured group and its concentration at T0 and at T10 is significantly lower in high than in low energy fractures. RANKL/OPG ratio is significantly higher in both controls than in fractured groups, and significantly increases after 10 weeks. IL-6 and TNF-alpha concentrations significantly decrease during fracture healing and are higher in high (group A) than in low energy fractures (group B). Significant differences were also found in both RUST score and LEM between groups A and B. Changes in TNF-alpha and IL-6 levels correlate with RUST and LEM in fragility and high energy fractures, while RANKL/OPG ratio is associated with these clinical parameters only in fragility fractures. These findings suggest that serum levels of IL-6, TNF-alpha, RANKL and OPG might be used to monitor the stages of fracture repair. Further studies will be needed to confirm the role of these cytokines in fracture repair.

Relationship between body composition, body mass index and bone mineral density in a large population of normal, osteopenic and osteoporotic women.

PURPOSE: The knowledge of factors modulating the behaviour of bone mass is crucial for preventing and treating osteoporotic disease; among these factors, body weight (BW) has been shown to be of primary importance in postmenopausal women. Nevertheless, the relative effects of body composition indices are still being debated. Our aim was to analyze the relationship between body mass index (BMI), fat and lean mass and bone mineral density (BMD) in a large population of women. Moreover, this study represents a first important report on reference standard values for body composition in Italian women. MATERIALS AND METHODS: Between 2005 and 2008, weight and height of 6,249 Italian women (aged 30-80 years) were measured and BMI was calculated; furthermore BMD, bone mineral content, fat and lean mass were measured by dual-energy X-ray absorptiometry. Individuals were divided into five groups by decades (group 1, 30.0-39.9; group 2, 40.0-49.9; group 3, 50.0-59.9; group 4, 60.0-69.9; group 5, 70.0-79.9). Differences among decades for all variables were calculated using a one-way analysis of variance (ANOVA) and Bonferroni test by the SPSS programme. RESULTS: Mean BW was 66.8±12.1 kg, mean height 159.1±6.3 cm and mean BMI 26.4±4.7 kg/m(2). According to BW and BMI, there was an increase of obesity with age, especially in women older than 50 years (p<0.001). Lean mass increased until 50 years of age but significantly decreased after this age (p<0.001). The percentage of osteopenia and osteoporosis in the examined population was 43.0% and 16.7%, respectively. CONCLUSIONS: Our data show that obesity significantly decreased the risk for osteoporosis but did not decrease the risk for osteopenia. It is strongly recommended that a strong policy regarding prevention of osteopenia and osteoporosis be commenced. An overall examination of our results suggests that both fat and lean body mass can influence bone mass and that their relative effect on bone could be modulated by their absolute amount and ratio to total BW.

Effect of a moderately hypoenergetic Mediterranean diet and exercise program on body cell mass and cardiovascular risk factors in obese women.

OBJECTIVE: To assess the effects of a moderately hypoenergetic Mediterranean diet (MHMD) and exercise program on body cell mass (BCM) and cardiovascular disease risk factors in obese women. SUBJECTS/METHODS: Forty-seven obese women, 39.7+/-13.2 years of age, with a body mass index (BMI)=30.7+/-6.0 kg/m(2), completed the study. The following were measured at baseline, 2 and 4 months: BCM, BCM index (BCMI), body weight, BMI, fat-free mass (FFM), fat mass (FM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) using bioelectrical impedance analysis; fasting blood glucose (FBG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations; systolic (SBP) and diastolic (DBP) blood pressure. RESULTS: Body weight, BMI, FM, TC and TG significantly decreased (P<0.001; P<0.002 (TG)) at 2 and 4 months. FFM, TBW, ECW, FBG and DBP significantly decreased at 2 months (P<0.05 (FFM); P<0.001). LDL-C significantly decreased (P<0.001), while HDL-C significantly increased (P<0.002) at 4 months. BCM, BCMI, ICW and SBP remained stable over time. CONCLUSION: BCM was preserved and cardiovascular disease risk factors improved in obese women placed on a MHMD and exercise program for 4 months.

Expression of a glucocorticoid receptor (DlGR1) in several tissues of the teleost fish Dicentrarchus labrax.

Since glucocorticoids have a role in maintaining the homeostatic status in fish, in the present paper mRNA expression (in situ hybridization) and tissue immunohistochemical localization of a glucocorticoid receptor (DlGR1) in several Dicentrarchus labrax organs are reported. Riboprobe and specific antibodies were prepared by using the DlGR1 that has been previously cloned and sequenced from peritoneal cavity leukocytes. Both mRNA and receptor were identified in head kidney, spleen, gills, intestine, heart and liver tissues. The functional roles of DlGR1 localization are discussed.

Monitoring chemical and physical stress using sea urchin immune cells.

Coelomocytes are the cells freely circulating in the body fluid contained in echinoderm coelom and constitute the defence system, which, in response to injuries, host invasion, and adverse conditions, is capable of chemotaxis, phagocytosis, and production of cytotoxic metabolites. Red and colourless amoebocytes, petaloid and philopodial phagocytes, and vibratile cells are the cell types that, in different proportions, constitute the mixed coelomocyte cell population found in sea urchins. Advances in cellular and molecular biology have made it possible to identify a number of specific proteins expressed in coelomocytes under resting conditions or when activated by experimentally induced stress. Only recently, coelomocytes have been used for pollution studies with the aim of introducing a new biosensor for detection of stress at both cellular and molecular levels, as sentinel of sea health. In this chapter, we briefly review the important features of these valuable cells and describe studies on their use in the laboratory and in the field for the assessment of chemical and physical pollution of the sea.

Ambulatory monitoring of blood pressure (AMBP) in patients with primary hyperparathyroidism.

The purpose of our study was to evaluate the behaviour of blood pressure (BP) by ambulatory monitoring of blood pressure (AMBP) in 53 patients with primary hyperparathyroidism (PHPT) compared to 100 essential hypertensive (EH) and 31 healthy subjects (HS). The correlations between calcium-phosphorus metabolism and haemodynamic parameters in all groups are included in the study. AMBP was performed using the oscillometric technique (Space-Labs, 90207, Redmond, WA, USA) and the following AMBP parameters were evaluated: average day time systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) (when awake), average night time SBP, DBP and HR (when asleep) and average 24-h-SBP, DBP and HR. The definition of 'dipper' or 'non-dipper' subjects was established if night time SBP and DBP fall was >10% and <10%, respectively. In total, 25 PHPT patients (47.2%) were hypertensive (HT-PHPT) and 28 PHPT (52.8%) were normotensive (NT-PHPT). Mean 24-h-SBP and DBP obtained by AMBP was higher in HT-PHPT (P < 0.05) and EH (P < 0.05) than in NT-PHPT and HS. The multiple linear regression has shown that in PHPT-HT patients ionized calcium is an independent factor for the rise of 24-h-DBP values (r: 0.497; P < 0.05) and daytime DBP values (r: 0.497; P < 0.05). In 56% of HT-PHPT patients there is an absence of physiological BP nocturnal fall ('non-dipper'), which is statistically significant (P < 0.05) compared with 'non-dipper' EH patients (30%). In conclusion, in our study the prevalence of hypertension in PHPT was 47%. AMBP revealed that the 'non-dipping 'pattern was much higher in HT-PHPT patients in respect to EH patients.

Acute hyperinsulinemia is associated with increased plasma adrenomedullin concentrations in uncomplicated obesity.

OBJECTIVE: Adrenomedullin (AM) is a potent hypotensive peptide which may be implicated in the insulin regulatory system. Acute hyperinsulinemia exerts no influence on plasma AM in normal subjects while no data on obese subjects has been reported. PURPOSE: The aim of the study was to investigate the effect of acute hyperinsulinemia on the plasma AM concentration in patients with uncomplicated obesity. RESEARCH METHODS: We measured the plasma AM levels in 23 obese subjects (BMI 41.9 +/- 9.8 kg/m2), 21 females and 2 males (mean age 31 +/- 7.2 years), before and during a euglycemic hyperinsulinemic clamp. The control group consisted of 43 healthy subjects (HS) (22 males and 21 females; mean age 38 +/- 12 years; BMI 23.3 +/- 3.2 kg/m2). RESULTS: Baseline plasma AM was found to be higher in obese subjects (20.4 +/- 8.4 pg/ml) than in normal subjects (11.3 +/- 0.8 pg/ml) (p < 0.001). A significant increase in the plasma AM levels was observed in obese subjects during acute hyperinsulinemia (from 20.4 +/- 8.4 pg/ml at 0 min to 26 +/- 8.9 pg/ml at 120 min, p < 0.02). Plasma AM concentrations were significantly correlated with insulin levels at 30 min (r = 0.44; p = 0.04) and 120 min (r = 0.40, p = 0.05) during the clamp. DISCUSSION: In conclusion, acute hyperinsulinemia induced a significant increase in the plasma levels of AM in uncomplicated obese subjects. Hyperinsulinemia may, at least in part, regulate levels of AM in obesity, explaining the high levels of the peptide in these subjects.

Adrenomedullin concentrations are elevated in plasma of patients with primary hyperparathyroidism.

The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 +/- 7.9 pg/mL) than in HS (11.3 +/- 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 +/- 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 +/- 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation.

Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma.

It has been demonstrated that adrenomedullin, a newly discovered peptide with structural similarity to calcitonin gene-related peptide (CGRP), is expressed in pituitary gland and affects basal and corticotropin (ACTH)-releasing factor (CRF)-stimulated ACTH release in animals, thus suggesting its potential role in regulating the hypothalamus-pituitary-adrenal axis. To evaluate whether ACTH and cortisol levels affect adrenomedullin production in humans, we studied 14 patients with Cushing's syndrome due to pituitary adenoma and 8 patients with Cushing's syndrome due to adrenal tumor, with measurement of circulating adrenomedullin by a specific radioimmunoassay (RIA). Adrenomedullin concentrations were significantly higher in patients with pituitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) and patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surgical treatment, plasma adrenomedullin decreased significantly. In one patient with Cushing's syndrome due to pituitary adenoma who underwent simultaneous sampling of the inferior petrosal venous sinuses, the adrenomedullin concentration was significantly higher in plasma collected from the side with the adenoma and increased after CRF administration (delta increase, 42.6%), according to ACTH levels. Our findings indicate that circulating adrenomedullin is increased in Cushing's disease, and the pituitary gland may represent the site of the elevated production of adrenomedullin in this condition.

[Effects of the combined raloxifene-sodium fluoride therapy on bone mass and bone turnover in women with postmenopausal osteoporosis]. / Effetti della terapia combinata raloxifene-fluoruri sulla massa ossea e sul turnover scheletrico in donne affette da osteoporosi post-menopausale.

BACKGROUND: Aim of the study was to compare the effects of raloxifene (RLX) therapy alone or with a combination of RLX and slow release sodium fluoride (SRNaF) on bone mineral density (BMD) and bone turnover, at 1 year. METHODS: Ninety-two consecutive postmenopausal women with osteoporosis (49-62 yr old) were randomly allocated to a group A (n=48; RLX 60 mg/day per os) or a group B (n=44; RLX 60 mg/day per os plus SRNaF 25 mg x 2/day per os); all participants received oral calcium carbonate (500 mg x 2/day) and vitamin D3 (400 UI x 2/day) too. Lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA) at time 0 (T0), after 6 (T6) and 12 (T12) months; at the same time, serum bone specific alkaline phosphatase (BALP) and urinary N-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6 and T12. RESULTS: Eighty-five women completed the study, 45 in group A and 40 in group B. In group B, after 1 year of treatment, we found a significant (p<0.01) increase in L1-L4 BMD (3.9+/-0.3%) respect to group A (2.8+/-0.1%); FN BMD in group B increased by 3.3+/-0.3% which was significantly different (p<0.01) from group A (2.3+/-0.1%), at 1 year. After 12 months of therapy, NTx/cr decreased significantly more (p<0.05) in group B (-36+/-2.6%) than group A (-29+/-2.0%); BALP levels increased in group B and decreased in group A: in group B BALP levels (11+/-1.2%) significantly increased (p<0.001) than group A (-2.1+/-0.1%), since 6th month. CONCLUSIONS: These data demonstrate that the combination of antiresorptive and bone-stimulating agents may dissociate bone resorption and bone formation and thus, by synergestic effect, induce a significative increase in BMD.

Plasma adrenomedullin concentrations in patients with renovascular or malignant hypertension.

AIM: The aim of the present study was to investigate the behaviour of plasma adrenomedullin (AM), a hypotensive peptide, in patients with malignant (MHT) and renovascular hypertension (RVH), 2 pathologic conditions in which renin-angiotensin system (RAS) is activated and to compare them with those in essential hypertensive patients (EHT) and normotensive subjects (NS). METHODS: Three groups of hypertensive patients have been studied: group 1 (4 patients with MHT), group 2 (10 patients with RVH), group 3 (24 patients with EHT) and 21 patients NS were enrolled as controls. In all patients, 10 ml vein blood samples were collected and AM was measured with specific radioimmunoassay. RESULTS: As expected, the plasma renin activity (PRA) levels in the RVH and MHT patients were significantly higher (p<0.0001) respect to NS and EHT. The mean plasma AM (+/-SD) concentrations in EHT (22.5+/-9.1 pg/ml) and RVH (46.8+/-19.4 pg/ml) were significantly (p<0.0001) higher than those in NS (13.7+/-6.1 pg/ml). The plasma AM concentrations were further elevated in MHT patients (107+/-12.3 pg/ml) and were significantly higher (p<0.0001) than those in EHT and RVH patients. In the MHT patients the elevated plasma AM levels, similarly to blood pressure and PRA values, declined after antihypertensive treatment (36.8+/-5.7 pg/ml; p<0.01). CONCLUSION: In conclusion, the findings demonstrated that the plasma AM concentrations were increased in proportion to the severity of arterial hypertension. RAS was activated in patients with MHT and RVH suggesting that activation of this system may contribute to increased in the plasma levels of AM.

[High circulating levels of adrenomedullin and endothelin-1 in obesity associated with arterial hypertension]. / Elevati livelli circolanti di adrenomedullina e di endotelina-1 nell'obesità associata ad ipertensione arteriosa.

BACKGROUND: The aim of the study was to investigate the behavior of two endothelial vasoactive peptides, adrenomedullin (vasodilator) and endothelin-1 (vasoconstrictor), in human obesity with and without arterial hypertension. METHODS: The study was carried out on 30 obese subjects (body mass index > 27 kg/m2) divided into two groups: 15 normotensive obese patients (10 males, 5 females, mean age 42 +/- 12 years) and 15 hypertensive obese patients (9 males, 6 females, mean age 42 +/- 13 years). The control group consisted of 21 normal subjects (12 males, 9 females, mean age 38 +/- 12 years) and of 16 patients with essential hypertension (10 males, 6 females, mean age 41 +/- 12 years) but without organ damage. All studied subjects were taking a normocaloric (20-22 kcal/kg/day), normosodic (120-140 mEq/day) and normopotassic (50-60 mEq/day) diet. Between 8.00 and 9.00 a.m., a venous blood sample was taken for the determination (radioimmunoassay) of plasma adrenomedullin and endothelin-1 concentrations. RESULTS: Plasma adrenomedullin levels in normal subjects (13.7 +/- 6.1 pg/ml) were similar to those in normotensive obese patients (14.8 +/- 7.2 pg/ml), whereas in hypertensive obese patients (22.5 +/- 9.1 pg/ml) and in those with essential hypertension (22.7 +/- 8.2 pg/ml) levels were significantly higher (ANOVA = 0.000, p < 0.05) than those of normal subjects and of normotensive obese patients. Moreover, endothelin-1 plasma concentrations were found to be significantly higher (ANOVA = 0.000, p < 0.05) in hypertensive obese patients (10.3 +/- 2.7 pg/ml) compared to normal subjects (6.5 +/- 2.4 pg/ml), normotensive obese patients (8.3 +/- 1.5 pg/ml) and to those with essential hypertension (8.5 +/- 2.9 pg/ml). In patients with essential hypertension, a positive correlation (r = 0.493, p < 0.05) was found between adrenomedullin and endothelin-1 plasma levels. CONCLUSIONS: These results revealed that in human obesity associated with arterial hypertension there is an increased production of plasma adrenomedullin and endothelin-1 that, with their opposite vasoactive properties (vasodilation/vasoconstriction), can contribute to this pathological association.

Primer reporte de necrosis avascular de cabeza femoral en una cabra (Capra aegagrus hircus) en el Perú / First report of avascular necrosis of the femoral head in a goat (Capra aegagrus hircus) in Peru

RESUMEN Se reporta el caso de una cabra macho de raza alpina de 7 meses de edad, que presentaba claudicación del miembro posterior derecho sin causa definida. Se realizaron los exámenes clínicos y radiográficos, sugiriendo luxación traumática o necrosis avascular de cabeza femoral con consecuente enfermedad degenerativa articular. Se realizó tratamiento quirúrgico mediante artroplastia por excisión de cabeza y cuello femoral. El estudio histopatológico mediante la coloración de hematoxilina y eosina describió: hueso necrótico, lagunas conteniendo osteocitos necróticos, además de médula ósea necrótica. Esta información comprobó el diagnóstico de necrosis avascular de la cabeza y cuello femoral. En el post quirúrgico, la recuperación clínica del paciente se consideró buena, mitigando el dolor y mejorando la función del miembro afectado. El presente caso se trata del primer reporte de esta enfermedad en caprinos en el Perú.

ABSTRACT It is reported the case of a 7-month-old male goat of alpine race, who presented claudication of the right hind limb without definite cause. Clinical and radiographic examinations were performed, suggesting traumatic dislocation or avascular necrosis of the femoral head with consequent degenerative joint disease. It was performed a surgical treatment by an arthroplasty by excision of the head and neck of femur. The histopathological study by staining hematoxylin and eosin described: necrotic bone, lacunae containing necrotic osteocytes, as well as necrotic bone marrow. This information proved the diagnosis of avascular necrosis of the femoral head and neck. In the post-surgical period, the clinical recovery of the patient was considered good, the pain was mitigated and the function of the affected limb was improved. The present case is the first report of this disease in goats in Peru.

Long-term effect of exercise on bone mineral density and body composition in post-menopausal ex-elite athletes: a retrospective study.

OBJECTIVES: The aim of this retrospective study was to determine the long-term effect of exercise on bone mineral density (BMD), bone mineral content (BMC) and body composition (BC) in post-menopausal women who were elite athletes during their youth compared with sedentary controls. SUBJECTS/METHODS: It is a retrospective study and carried out in an outpatient clinic. A total of 48 post-menopausal women (54-73 years of age) were enrolled. Ex-elite athletes with long-term (>20 years) histories of significant training and performance were divided into two groups: weight-bearing sports (runners, n=12) and non-weight-bearing sports (swimmers, n=12). The athletes were age matched with sedentary controls (n=24). BMD, BMC and BC were measured using dual-energy X-ray absorptiometry. Healthcare and sport activity histories were evaluated using a questionnaire. RESULTS: No significant differences were found with regard to body weight, height, body mass index and hours of activity between the two groups of athletes. There were no significant differences in activity levels between athletes and controls at the time of this study. BMD and BMC were not significantly different between athletes; they were significantly higher in athletes than in controls (P<0.001). Although the ex-athletes did not significantly differ in BC, left and right lean arm mass and arm BMD were significantly higher in swimmers than in runners (P<0.0001). CONCLUSIONS: The high level of physical activity observed in female athletes is associated with improved muscle mass, BMD and BMC, and physical activity during youth seems to have a beneficial effect on bone mass and helps to prevent bone loss due to aging.

Open medial dislocation of the ankle without fracture.

A 20-year-old man sustained an open medial dislocation of the ankle without an associated fracture after a low-energy inversion injury. Prompt debridement and reduction with primary wound closure of the skin were performed without suture of the capsule. Immobilisation in a non-weight-bearing cast for 30 days followed by ankle bracing for two weeks and subsequent physiotherapy, produced full functional recovery by three months. At follow-up at one year there was a full range of pain-free movement, although the radiographs and MR scan showed early post-traumatic degenerative change at the medial aspect of the tibiotalar and the calcaneocuboid joints.