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AbstractSatellite cells (SCs) are undifferentiated skeletal muscle cells that allow muscular growth and regeneration. Since their first description, SCs were simply considered myogenic precursors, but now it is widely accepted that SCs are a heterogeneous stem cell population characterized by plasticity and self-renewal. In this report we focus on SCs capacity to undergo adipogenic differentiation both spontaneous and induced by adipogenic factors. Understanding SC behavior is especially important because their adipogenic potential could represent a pathophysiological explanation for the intramuscular fat depots and associated insulin resistance that characterize many metabolic diseases and age-related sarcopenia. Moreover, SC are a therapeutic promise for neuromuscular diseases in the context of tissue engineering, representing an interesting cell source for implantation.

OBJECTIVE: Glucocorticoids were found to inhibit adiponectin gene expression and secretion both in vitro and in animal models. We evaluated first the acute effect of i.v. glucocorticoids on adiponectin in normal subjects and secondly plasma adiponectin levels in a series of patients with Cushing's syndrome compared with controls. DESIGN AND METHODS: Hydrocortisone (25 mg) was administered i.v. to five healthy volunteers, with blood samples taken at -15, 0, 30, 60, 120 and 180 min. Twenty-one patients with Cushing's syndrome were divided in two groups: one with 11 obese and the other with 10 non-obese Cushing's patients. Each group was compared with controls that were matched for sex, age, body mass index, waist circumference, glucose, insulin, lipid levels and blood pressure. RESULTS: In normal subjects, hydrocortisone produced a decrease in adiponectin at 30 and 60 min, compared with placebo (P<0.05). Adiponectin was lower in non-obese Cushing's patients than in non-obese controls (P<0.004). In contrast, there was no difference in adiponectin levels in obese Cushing's patients and in obese controls. Adiponectin was inversely correlated (P<0.05) with homeostasis model assessment index in both obese and non-obese Cushing's patients; in non-obese Cushing's patients only, adiponectin was inversely correlated with urinary cortisol (P<0.05). CONCLUSIONS: Glucocorticoids inhibit adiponectin in man, as shown by both exogenous administration to healthy subjects and endogenous cortisol hyperproduction. Similar levels of adiponectin in obese Cushing's patients and their obese controls indicate that obesity per se may act as a predominant factor in masking the relationship between adiponectin and cortisol.

OBJECTIVE: Little is known about the physiological role and the regulation of uncoupling proteins-2 and -3 (UCP-2 and -3) in adipose tissue. We investigated whether the expression of UCP-2 and -3 in adipose tissue was affected by weight loss due to a biliopancreatic diversion (BPD) and related to the daily energy expenditure (24-h EE). DESIGN: Ten morbidly obese subjects (mean body mass index +/- s.e.m.=49.80 +/- 2.51 kg/m(2)) were studied before and 18+/-2 Months after BPD. METHODS: We determined body composition using tritiated water and 24-h EE in a respiratory chamber. Adipose tissue UCP-2 and -3 mRNA, plasma insulin, glucose, free fatty acids (NEFA), free triiodothyronine (FT3), free thyroxine (FT4) and leptin were assayed before and after BPD. RESULTS: BPD treatment resulted in a marked weight loss (P<0.001) mainly due to a fat mass reduction. A significant decrease in 24-h EE/fat-free mass (FFM) (P<0.05) and in UCP-2 (P<0.05) and UCP-3 (P<0.05) mRNA was observed. A significant reduction in plasma insulin, glucose, NEFA, FT3, FT4 and leptin was seen after BPD. The decline in plasma leptin and FFA was tightly correlated with the decrease in both UCP-2 and -3. A significant correlation was found between changes in FT3 and variations in 24-h EE (r=0.64, P<0.05). In a multiple-regression analysis changes in 24-h EE/FFM after BPD were significantly correlated with changes in UCP-3 expression (P<0.05). CONCLUSION: These findings suggest that UCPs in adipose tissue may play a role in the reduction in 24-h EE observed in post-obese individuals.

Objective:Obesity‐related insulin resistance is closely associated with visceral fat accumulation. Several adipocyte‐secreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection. Research Methods and Procedures:We determined adiponectin and resistin expressions in visceral (VAT) and subcutaneous adipose tissue of lean and obese Zucker (fa/fa) rats using reverse‐transcription polymerase chain reaction. Moreover, we analyzed the variations after body‐weight reduction in food‐restricted obese rats. Results:Resistin and adiponectin expression was significantly lower in VAT of genetically obese in comparison with lean rats; no differences were observed when subcutaneous adipose tissues of the same animals were compared. Weight loss resulted in an increase of adiponectin expression in VAT, whereas a further significant decrease in resistin mRNA level was observed. Resistin is also present and equally expressed in splenocytes of lean and obese rats. Discussion:Adiponectin and resistin are down‐regulated in VAT of obese rats. Adiponectin expression is restored to normal levels after body‐weight reduction, supporting its link with obesity‐related insulin resistance. On the contrary, the further decrease of resistin mRNA after weight loss does not support the hypothesis that resistin may play a causative role in insulin resistance in obese rats. Moreover, we demonstrated the presence of resistin in immunocompetent cells in both humans and rats, thus adding another factor to the list of molecules that adipose tissue shares with the immune system.

The aim of this study was to establish the duration and annual rate of menopause-related bone loss and to investigate the relationship between bone turnover and bone loss in early healthy postmenopausal women. The rate of change in bone mineral density (BMD) at the lumbar spine and in bone turnover was measured twice at the exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) and by the determination of plasma alkaline phosphatase levels (ALP) and fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr), respectively, in 123 healthy premenopausal and postmenopausal women 45–60 years of age. The subjects were divided into nine groups according to their menstrual status and years since menopause (YSM). Annual bone loss at the lumbar spine of women who were menopausal for 1, 2, 3, 4, and 5 years was −2.62 ± 0.37 (95% confidence interval −3.66, −1.58), −3.87 ± 0.96 (−6.02, −1.73), −2.50 ± 0.37 (−3.29, −1.70), −2.86 ± 0.73 (−4.44, −1.27), and −1.54 ± 0.41 (−2.42, −0.66), respectively, and was significantly less than zero. But, the annual bone loss of women who were premenopausal or menopausal for 6, 7, and 8 years was −0.76 ± 0.60 (−2.04, +0.53), −1.16 ± 0.68 (−2.61, +0.29), 0.24 ± 0.48 (−0.78, +1.26), and 0.16 ± 0.63 (−1.18, −1.49), respectively, and was not significantly different from zero. These results demonstrate that the early hormone-dependent bone loss commences in the first year after menopause and is arrested within 6 years after the onset of menopause. The overall bone loss for this phase is estimated to be approximately 15%. Annual change in ALP and OHPr/Cr seems to indicate that bone resorption prevails on bone formation in the first 2 YSM, whereas osteoblastic activity relatively prevails from YSM 3 to YSM 5, which explains the progressive repairing of the imbalance between bone resorption and formation.

Summary Bone tissue is a source of growth factors; among them, insulin-like growth factor I (IGF-I) is probably an important local regulator of bone formation. This study has been carried out in order to assess the effects of natural menopause on plasma concentrations of IGF-I in the first 6 years after the cessation of gonadal function independent of age. We also examined the relationship between plasma IGF-1 levels and bone mineral density (BMD) measured at the lumbar spine (LS), at the ultradistal radius (UDR), and at the junction of the distal and middle thirds of the radius (MR). Sixty-seven healthy nonobese women, aged 45–55, were studied (premenopausal n = 21; postmenopausal n = 46, from 1 to 6 years since menopause). Plasma IGF-I levels were measured by RIA, after acid-ethanol extraction. BMD of the forearm was measured by dual-photon densitometer and BMD of the LS was assessed by quantitative digital radiography. Mean values of IGF-I plasma levels were significantly reduced in postmenopausal women compared to the premenopausal group. Menopausal duration did not influence IGF-I plasma levels in postmenopausal women. We also found a positive correlation between IGF-I levels and BMD measured at MR both in pre- and postmenopausal women, while a correlation with LS and UDR-BMD was found only in fertile subjects. The results show that IGF-I plasma levels decrease immediately after menopause, since significantly lower levels are reached in the first years. The correlations found between plasma IGF-I levels and BMD suggest a possible role of reduced IGF-I in bone loss at particular skeletal sites.

This study was carried out to investigate early effects of parathyroidectomy (PTx) on bone matrix collagen metabolism. Eleven patients suffering from primary hyperparathyroidism were studied by measuring urinary excretion of hydroxyproline (OHPr) and cAMP in samples collected before PTx and, on the day of surgery, at intervals of 1–3 h for the first 10 h and then at longer intervals. In six patients nondialyzable urinary OHPr and free plasma aminoacid levels were also assayed. We found that the average period required for OHPr/Cr ratio and plasma OHPr to reach normal values was longer than the mean time required for cAMP/Cr ratio to reach normal limits. In all patients the total amount of nondialyzable OHPr decreased in the first 24 h after PTx but thereafter a daily increase in the urinary excretion of nondialyzable component was seen, so that the fractional amount of nondialyzable OHPr in the fourth postoperative day (26.8 ±5.2 SE) was significantly higher than that of preoperative one (6.1 ± 1.0; p< 0.02). Our results confirm that PTx induces a reduction in the rate of bone collagen resorption and indicate that changes of OHPr/Cr ratio and free plasma OHPr values may be considered useful indices of successful parathyroid surgery, even though they lag behind those of cAMP. The different behavior of total and nondialyzable OHPr after surgery indicates that acute deficiency of parathyroid hormone induces a positive uncoupling of the two processes of bone remodeling, thus supporting the view that the acute direct effect of the hormone on bone formation is an inhibition of this process.

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio ( felt to be a marker of bone résorption) rise immediately at the first control (19.7±11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean±SD % measured yearly bone loss was −2.83±2.6. There was a highly significant correlation between initial and final BMD values (r= 0.908, p<0.001; r2= 82.5) and a weak inverse correlation (r= −0.298, p<0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone résorption; furthermore, in the immediate postmenopausal period, the actual bone massshould be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3±15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2±121.9 pmoles bone collagen equivalents/pinoles creatinine) were significantly higher (p<0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4±1.8) and the fasting hydroxyproline/creatinine ratio (1.45±2.0) was significantly lower (p<0.02) in respect to that of NTx Z score values (3.3±3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0±3.9), serum alkaline phosphatase activity (2.6±2.6) and urinary calcium/creatinine ratio (3.2±3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p<0.01) and ultradistal radius bone mineral density (p<0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p<0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.

The study investigated possible menopause-related changes in circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and their relationship with insulin-like growth factor I (IGF-I) plasma levels. Forty-three healthy women, aged 45–55 years, were studied (22 premenopausal and 21 postmeno-pausal, matched for age and body mass index); in all subjects plasma IGF-I and IGFBP-3 levels were measured by radioimmunoassay. No difference was found between mean IGFBP-3 plasma levels in the two groups studied (premenopausal 3.42±0.49 v postmenopausal 3.46±0.58 mg/l), while mean IGF-I levels were significantly lower in postmenopausal as compared with premenopausal women (136.7±37.86 v 175.7±51.91 ng/ml,p<0.02). Multiple regression analysis showed no significant effect of age, body mass index and years since menopause on IGFBP-3 levels; however, considering the IGF-I/IGFBP-3 ratio as a possible parameter of circulating free somatomedin C, an inverse correlation was found with years since menopause (n=43,r=-0.499,p<0.001). We conclude that lack of oestrogen induces different effects on circulating IGF-I and IGFBP-3, possibly reflecting a real decrease in IGF-I activity.

This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunora-diometric assay (n=42, r=0.67, p<0.001) and a widely used midmolecule radioimmunoassay (n=21, r=0.78; p<0.001). Similar good correlations were found in primary hyperparathyroidism patients (ICMA vs immunoradiometric assay r=0.74; p<0.001; ICMA vs midmolecule assay r=0.77; p<0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule. Finally, shortening incubation periods so that overall assay time was limited to as little as 30 minutes gave the possibility of providing good discrimination between high PTH levels typical of severe primary hyperparathyroidism and normal values or the suppressed levels found in hypercalcemic cancer patients. In conclusion, the measurement of PTH levels using an ICMA method seems to provide a valuable means of investigating parathyroid physiology and mineral metabolism disorders.

Early effects of parathyroid hormone (PTH) deficiency were studied in 12 patients with primary hyperparathyroidism due to single parathyroid adenoma by following the precise time course of changes in plasma calcium (Ca) and immunoreactive parathyroid hormone (iPTH) after parathyroid surgery and by prelabeling 2 patients with radiocalcium (Ca*). Surgical removal of the adenoma was immediately followed by a sudden increase in plasma Ca which preceded the usual fall. The increase in plasma Ca commenced simultaneously with the fall in iPTH and was accompanied by a parallel increase in specific activity (sp. act.) of plasma Ca*. Specific activity continued to rise for 2 h in both prelabeled patients, whereas blood calcium was already falling thereafter reaching a markedly low removal rate constant as long as plasma Ca decreased. When plasma Ca began to rise, sp. act. resumed a descending course.

Minisola S, Romagnoli E, Scarnecchia L, Rosso R, Pacitti MT, Scarda A, Mazzuoli G. Serum carboxyterminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. Eur I Endocrinol 1994;130:587–91. ISSN 0804-4643This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 ± 3.1 semyears) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 ± 27 semμg/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.S Minisola, Istituto di II Clinical Medica, Policlinico Umberto I, Via del Policlinico 155, 00161 Rome, Italy

Plasma levels of calcium, phosphorus, immunoreactive calcitonin (iCT), immunoreactive parathyroid hormone (iPTH), and carcinoembryonic antigen (CEA) were measured in patients affected by tumors of various organs: 22 breast, 41 lung, 23 kidney, 16 gastrointestinal tract, and 8 other types. iCT plasma level was elevated in 53.6% of patients with bronchogenic cancer, in 31.8% with breast cancer, in 65.3% with renal cancer, in 31.2% with gastrointestinal cancer, and in 62.5% with other tumors. Blood calcium level was increased in 6 patients suffering from lung cancer; iCT plasma level was increased in all but one of these subjects. iPTH plasma level, measured in 35 patients, was elevated only in one case, in which normo-calcemia was present. Our results demonstrate that plasma iCT is increased in a high percentage of cancer patients and that it is probably a good tumor marker. The simultaneous measurement of CEA increases the diagnostic probability of the individual marker. The incidence of laboratory findings suggestive of primary or ectopic hyperparathyroidism was very low in our series of patients.

Presents letters to the editor in response to an article published in the May 9, 2005 edition of "Newsweek." Responses to the article "A Scandal Spreads," on abuse of the Koran by United States officials at Guantánamo Bay.

Quantitative ultrasound measurements were done in a group of 26 patients (4 males and 22 females, aged 55.4 ±14.2 years) with primary hyperparathyroidism, and the results were compared with bone mineral density (BMD) carried out at various skeletal sites. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were measured with the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). Mean ± SD values of SOS, BUA and stiffness in patients with primary hyperparathyroidism were 1522±38 m/seconds, 111±16 dB/MHz, and 80.4±19.8%, respectively. There were significant differences of mean T-score BUA values (-0.63±1.11) compared with corresponding T-score BMD values found at ultradistal (-1.85±1.73, P<0.01), proximal radius (-2.40±2.13, P<0.001), and total femoral (-1.60±1.32, P<0.001) sites. Correlation coefficients between both SOS and BUA values with BMD measurements at specific skeletal sites varied, but stiffness correlated moderately (0.6–0.9) with BMD. Our data strongly indicate that in patients with primary hyperparathyroidism, bone structure of some skeletal sites, as evaluated by BUA measurement, is compromised to a lesser extent than BMD. In this respect it is interesting to note the lack of significant differences (in terms of mean T-score values) in the comparison of two sites of mostly trabecular composition, that is, the lumbar level (-1.17±1.54) and the femoral Ward's triangle (-0.99±1.25). Our results seem to lend further support to the hypothesis that in primary hyperparathyroidism cancellous bone architecture might be preferentially maintained. Quantitative ultrasound techniques appear to complement, and could possibly substitute for, existing bone densitometry examinations.

Presents letters to the editor in response to articles and topics discussed in previous issues. Reaction of readers to a story which alleged that American interrogators at Guantánamo Bay flushed a Koran down the toilet during interrogation of Muslim prisoners; "The 100 Best High Schools in America," which evaluated the quality of high school education in the U.S.