Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease.

BACKGROUND AND AIMS: Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease. METHODS AND RESULTS: 86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m(-2)), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p < 0.03 and p < 0.03, respectively). CONCLUSIONS: CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats.

AIMS/HYPOTHESIS: Visceral and intermuscular adipose tissue (IMAT) depots account for most obesity-related metabolic and cardiovascular complications. Muscle satellite cells (SCs) are mesenchymal stem cells giving rise to myotubes and also to adipocytes, suggesting their possible contribution to IMAT origin and expansion. We investigated the myogenic differentiation of SCs and the adipogenic potential of both preadipocytes and SCs from genetically obese Zucker rats (fa/fa), focusing on the role of Wnt signaling in these differentiation processes. METHODS: SCs were isolated by single-fiber technique from flexor digitorum brevis muscle and preadipocytes were extracted from subcutaneous adipose tissue (AT). Morphological features and gene expression profile were evaluated during in vitro myogenesis and adipogenesis. Wingless-type MMTV integration site family member 10b (Wnt10b) expression was quantified by quantitative PCR in skeletal muscle and AT. RESULTS: We did not observe any difference in the proliferation rate and in the myogenic differentiation of SCs from obese and lean rats. However, a decreased insulin-induced glucose uptake was present in myotubes originating from fa/fa rats. Under adipogenic conditions, preadipocytes and SCs of obese animals displayed an enhanced adipogenesis. Wnt10b expression was reduced in obese rats in both muscle and AT. CONCLUSIONS/INTERPRETATION: Our data suggest that the increase in different fat depots including IMAT and the reduced muscle insulin sensitivity, the major phenotypical alteration of obese Zucker rats, could be ascribed to an intrinsic defect, either genetically determined or acquired, still present in both muscle and fat precursors. The involvement of Wnt10b as a regulator of both adipogenesis and muscle-to-fat conversion is suggested.

Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study.

BACKGROUND AND AIM: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. METHODS: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. RESULTS: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. CONCLUSIONS: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). DESIGN AND PATIENTS: Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD. INTERVENTIONS: NAC 1200 mg/day, 600 mg/day or placebo administered once daily for 10 days. MAIN OUTCOME MEASURES: The primary objective was to assess the proportion of patients with normalised C-reactive protein (CRP) levels. Also assessed were effects on interleukin (IL)-8 levels, lung function and symptoms. RESULTS: Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo (52% and 90% vs 19% of patients; p

Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion.

A reduced lipid oxidative capacity is considered a risk factor for the development of obesity, but a further impairment of lipid oxidative capacity is observed after weight loss. We aimed to define the mechanisms underlying this phenomenon in skeletal muscle and in particular to study the mitochondrial and peroxisomal lipid oxidative pathways. Thus we measured intramyocellular triglyceride content (IMTG) and the expression of genes of lipid oxidation [peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis (acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly obese patients before and after biliopancreatic diversion. Weight reduction significantly decreased IMTG while increasing insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a decline in lipid oxidation, as assessed by respiratory chamber, were observed. Weight loss reduced the expression of peroxisome proliferator-activated receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate that a defect of both peroxisomal and mitochondrial oxidative pathways at the muscular level may contribute to the reduced fat oxidation in obese subjects after biliopancreatic diversion. They also suggest that a depression of the de novo lipogenesis may account for IMTG depletion.

Annual skeletal balance and metabolic bone marker changes in healthy early postmenopausal women: results of a prospective study.

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.

Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery.

This 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 SEM years) 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 SEM micrograms/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.

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures.

OBJECTIVE: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). METHOD: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n = 24), mean age 33.7 +/- 8.1 years; (2) postmenopausal women (n = 32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than -2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7 +/- 7.9 years; and years since menopause (ysm), 12.6 +/- 8.3); (3) postmenopausal women (n = 32, including 19 patients with fractures) whose BMD values in terms of T score, were below -2.5 S.D. (mean age 62.9 +/- 8.6 years; and ysm 15.9 +/- 9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. RESULTS: There were significant differences amongst the three groups in mean ALP (P < 0.001, by analysis of variance) TRAP (P < 0.006) and NTx/Cr (P < 0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r = -0.392, P < 0.001; r = -0.447, P < 0.001 and r = -0.327, P < 0.002, respectively) and ysm (r = -0.374, P < 0.001; r = -0.474, P < 0.001 and r = -0.333, P < 0.002). CONCLUSIONS: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.

Plasma calcitonin and tumors.

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.

[Effects of the length of radioiodine treatment of hyperthyroidism on the distribution of blood levels of calcium and phosphorus as a function of sex and age]. / Effetti a distanza del trattamento con radioiodio dell'ipertiroidismo sulla distribuzione dei livelli ematici del calcio e del fosforo in funzione del sesso e dell'età. Rilievi statistici.

An evaluation was made of the incidence of hypoparathyroidism after 131I management of hyperthyroidism and of the effect of irradiation on the relation between blood calcium, phosphorus and proteins and age in normal subjects. 356 treated patients and 216 controls were examined. Serum calcium was determined from 2 to 6 yr after treatment. It was found that calcium values decrease with age in males, wherease in women this phenomenon is less marked and, indeed, is no longer apparent over the age of 30. In the normal male, phosphrous also decreases with age, while in females there is a fall until the age of 30-40 yr, followed by a rise. Only 1 subject with a value of 8.45 mg calcium/100 ml was noted in the treated group and there was no significant difference between the means for the two groups, suggesting that parathyroid insufficiency is a virtually non-existent complication of the 131I treatment of hyperthyroidism. The relation between blood calcium and phosphorus and age in the treated group was examined with reference to subjects with normal thyroid function only. In the case of calcium, values were no longer related to age after treatment in males, while phosphorus values fell to below those observed in females, coupled with an increase in function of age as in women, though this itself was not statistically significant. Treatment also suppressed the relation between total blood proteins and age noted in the normal male. None of the parameters considered displayed any significant changes in the treated females. It would thus seem that 131I abolishes the differences in blood calcium and phosphorus mean values and age-linked patterns normally found between males and females.

Rosiglitazone modifies the adipogenic potential of human muscle satellite cells.

AIMS/HYPOTHESIS: Satellite cells are responsible for postnatal skeletal muscle regeneration. It has been demonstrated that mouse satellite cells behave as multipotent stem cells. We studied the differentiation capacities of human satellite cells and evaluated the effect of the insulin sensitiser rosiglitazone, a well known peroxisome proliferative activated receptor gamma (PPARG) agonist, on their adipogenic conversion. SUBJECTS, MATERIALS AND METHODS: We obtained human satellite cells from human muscle biopsies of healthy subjects by single-fibre isolation and cultured them under myogenic, osteogenic and adipogenic conditions. Moreover, we compared the morphological features and the adipose-specific gene expression profiling, as assessed by quantitative PCR, between adipocytes differentiated from human satellite cells and those obtained from the stromal vascular fraction of human visceral fat. RESULTS: We proved by morphological analysis, mRNA expression and immunohistochemistry that human satellite cells are able to differentiate into myotubes, adipocytes and osteocytes. The addition of rosiglitazone to the adipogenic medium strongly activated PPARG expression and enhanced adipogenesis in human satellite cells, but did not in itself trigger the complete adipogenic programme. Moreover, we observed a decrease in wingless-type MMTV integration site family member 10B and an upregulation of growth differentiation factor 8 expression, both being independent of PPARG activation. CONCLUSIONS/INTERPRETATION: Human satellite cells possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle in pathological conditions such as obesity, type 2 diabetes and ageing-related sarcopenia. Rosiglitazone treatment, while enhancing adipogenesis, induces a more favourable pattern of adipocytokine expression in satellite-derived fat cells. This could partially counteract the worsening effect of intermuscular adipose tissue depots on muscle insulin sensitivity.

WNT10B mutations in human obesity.

AIMS/HYPOTHESIS: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. SUBJECTS AND METHODS: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. RESULTS: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. CONCLUSIONS/INTERPRETATION: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

Serum osteocalcin in primary hyperparathyroidism: short-term effect of surgery.

This study has been carried out in order to evaluate both serum osteocalcin levels in primary hyperparathyroidism and their changes following surgery. Twenty-one consecutive patients were studied (12 females and 9 males, aged 46 +/- 17 years). Preoperatively, a better correlation was found between serum osteocalcin and serum alkaline phosphatase activity (r = 0.79, p less than 0.001) than between serum osteocalcin and the 24-hour urinary hydroxyproline/creatine ratio (r = 0.55, p less than 0.05). Following the surgical removal of hyperfunctioning parathyroid tissue, a modest but significant decrease was observed in the serum levels of osteocalcin; this reached a nadir during the 1st or 2nd day after the removal of the adenoma. The mean levels then tended to rise, so that the values measured on the 7th day after parathyroidectomy (12.4 +/- 2.5 ng/ml) were not significantly different in respect to basal values (13.6 +/- 2.7 ng/ml). A parallel pattern was also noted as concerns the serum alkaline phosphatase activity. On the contrary, mean values of serum immunoreactive parathyroid hormone (243 +/- 78 vs. 58 +/- 11 pmol/l; p less than 0.02) and serum calcium (12.4 +/- 0.5 vs. 9.2 +/- 0.3 mg/dl; p less than 0.01) were significantly reduced and mean values of serum phosphorus (2.4 +/- 0.2 vs. 3.1 +/- 0.2 mg/dl; p less than 0.001) significantly higher in comparison to basal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical picture accompanying sclerotic bone metastases of prostatic origin.

This study was carried out to evaluate the metabolic consequences of osteosclerotic skeletal metastases of prostatic origin in a homogeneous group of patients. We found significantly increased mean values of serum alkaline phosphatase activity and significantly reduced mean values of serum phosphate, 24-h urinary calcium, fasting calcium excretion and TmP/GFR in cancer patients with respect to age-matched controls. Mean serum immunoreactive parathyroid hormone (iPTH) levels were raised, with two patients showing increased values of the hormone above our normal limits. Our findings indicate that mild secondary hyperparathyroidism is a feature of these patients. However, it cannot be excluded that both the reduced serum phosphate and TmP/GFR values may be related, at least in some cases, to the effects of the tumour itself on tubular reabsorption of phosphate.

Quantitative ultrasound assessment of bone in patients with primary hyperparathyroidism.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of intestinal absorption of calcium by means of double-isotope methods and oral administration of the tracer]. / Valutazione dell'assorbimento intestinale del calcio me diante i metodi del doppio isotopo e la somministrazione orale del tracciante.

The percent intestinal absorption of calcium was measured in normal volunteers and in patients with idiopathic hypercalciuria employing the deconvolution method, the ratio of the two administered isotopes at equilibrium and the percent of dose present in plasma 2 hr after oral administration of the tracer. Comparison of results obtained showed that the technique based on the ratio between the two radioisotopes overestimates intestinal absorption by about 9% with respect to values calculated with the deconvolution method, but gives results comparable to those determined by oral administration of the isotope. The percent dose of the tracer 2 h after i.v. administration is closely correlated with the size of the miscible calcium pool. A less significant correlation exists between the size of the pool and percent of the dose 2 h after oral administration.

[Studies of the half-life of plasma parathyroid hormone: rate of disappearance of immunoreactive fragments of the hormone after surgical removal of the parathyroid adenoma in primary hyperparathyroidism]. / Studi su l'emivita del paratormone plasmatico: velocita' di scomparsa dei frammenti immunoreattivi dell'ormone dopo asportazione chirurgica di adenoma paratiroideo nell'iperparatiroidismo primitivo.

The disappearance rate of immunoreactive plasma parathyroid hormone (iPTH) was studied, employing two different antisera, following removal of parathyroid adenoma in patients with primary hyperparathyroidism. One antisera contained antibodies against both the NH2 region and the COOH terminal of the molecule (antiserum 211/32, Wellcome Laboratories), the other contained antibodies against antigenic sites of the terminal COOH portion (Immuno Nuclear Corporation antiserum). The iPTH plasma level dropped in all patients following removal of the adenoma. The half-life was longer than that of the native hormone and shorter than that of the terminal fragment with both antisera, being 38.8 min for the 211/32 and 32.9 min for the I.N.C. antiserum. Whilst this finding might be expected for the 211/32 antiserum, on account of its characteristics, it is difficult to offer an explanation for the observed half-life of the I.N.C. anti serum which is specific for the terminal COOH region. These results appear to suggest that the terminal COOH fragment may be further metabolized and that its longer half-life, observed by other authors, is due to the antisera used recognizing the antigenic sites in a fragment smaller than the terminal COOH portion of the molecule, rather than to the effective half-life of the entire fragment.

[Values and limitations of the radioimmunological determination of plasma parathyroid hormone in the study of the functional activity of the parathyroid glands]. / Valori e limiti del dosaggio radioimmunologico del paratormone plasmatico nello studio dell'attivita' funziona le delle ghiandole paratiroidi.

Aim of the present study was to establish the limits and difficulties prevailing in RIA of PTH due to different specificity of antisera. Studies were carried out on normal volunteers and 36 patients with primary hyperparathyroidism (HPT) employing two different assay techniques a) 211/32 antiserum from Wellcome Lab. and b) Immuno Nuclear Corporation Kit. Plasma iPTH values were higher in most primary HPT patients than in normal subjects with both techniques. It is possible nevertheless to differentiate the primary HPT patients with normal plasma iPTH values from normal subjects by correlating plasma iPTH values with corresponding serum calcium values.