Is lead in tap water still a public health problem? An observational study in Glasgow.

OBJECTIVE: To assess the relation between tap water lead and maternal blood lead concentrations and assess the exposure of infants to lead in tap water in a water supply area subjected to maximal water treatment to reduce plumbosolvency. DESIGN: Postal questionnaire survey and collection of kettle water from a representative sample of mothers; blood and further water samples were collected in a random sample of households and households with raised water lead concentrations. SETTING: Loch Katrine water supply area, Glasgow. SUBJECTS: 1812 mothers with a live infant born between October 1991 and September 1992. Blood lead concentrations were measured in 342 mothers. MAIN OUTCOME MEASURES: Mean geometric blood lead concentrations and the prevalence of raised tap water lead concentration. RESULTS: 17% of households had water lead concentration of 10 micrograms/l (48.3 nmol/l) or more in 1993 compared with 49% of households in 1981. Tap water lead remained the main correlate or raised maternal blood lead concentrations and accounted for 62% and 76% of cases of maternal blood lead concentrations above 5 and 10 micrograms/dl (0.24 and 0.48 mumol/l) respectively. The geometric mean maternal blood lead concentration was 3.65 micrograms/dl (0.18 mumol/l) in a random sample of mothers and 3.16 micrograms/dl (0.15 mumol/l) in mothers whose tap water lead concentrations were consistently below 2 micrograms/l (9.7 nmol/l). No mother in the study had a blood lead concentration above 25 micrograms/dl (1.21 mumol/l). An estimated 13% of infants were exposed via bottle feeds to tap water lead concentrations exceeding the World Health Organisation''s guideline of 10 micrograms/l (48.3 nmol/l). CONCLUSIONS: Tap water lead and maternal blood led concentrations in the Loch Katrine water supply area have fallen substantially since the early 1980s. Maternal blood lead concentrations are well within limits currently considered safe for human health. Tap water lead is still a public health problem in relation to the lead exposure of bottle fed infants.     

Embryotoxicity of fenbendazole in Paracentrotus lividus

The aim of the present work was to evaluate the embryotoxicity of Fenbendazole, a benzimidazole carbamate-derived anthelmintic drug widely employed in Veterinary Medicine, by using the embryonal development of Paracentrotus lividus (sea urchin) as a experimental model. Embryos were obtained by in vitro eggs fertilization and cultured in seawater. Five embryo suspensions were added by Fenbendazole reaching a final concentration of 5 micrograms/l, 7.5 micrograms/l, 10 micrograms/l, 12.5 micrograms/l and 25 micrograms/l; a suspension was kept drug-free as a control. Embryo development was evaluated by microscopical examination of suspensions at 3 and 40 hours. Our results show that a concentration of 5 micrograms/l of the drug determines a considerable delay of the embryonal development in the 95 percent of the elements observed, and a concentration of 25 micrograms/l produces a block of the embryogenesis at the phase of morula and blastula in all embryos. Results confirm that the effects observed are probably due to an extended inhibition of several enzyme complexes of the embryo cells.     

Effects of tributyltin compounds on ionic regulation and gill ATPase activity in estuarine fish

1. Striped bass (Morone saxatilis) were exposed to 0, 0.10, 0.34, or 1.09 micrograms/l tributyltin (TBT) for 14 days. Gill Mg2+ ATPase and serum Na+, K+, Ca2+ and Mg2+ were not altered. Na+K+ATPase was significantly (P less than 0.05) increased (+48%) at 0.10 microgram/l. 2. In striped bass gill homogenates exposed to TBT in vitro, there was significant inhibition of Na+K+ATPase at 106.0 micrograms/l (17.2%) and Mg2+ATPase at 53.0 and 106.0 micrograms/l (16.0% and 24.3%, respectively). 3. In mummichog (Fundulus heteroclitus) gill homogenates, there was significant inhibition of Na+K+ATPase at 25.3 and 50.5 micrograms/l (10.9% and 16.1%) and Mg2+ATPase at 5.1, 25.3, and 50.5 micrograms/l (26.7%, 32.2%, and 36.2%).     

Nuclear thyroxine and triiodothyronine binding in mononuclear cells in dependence of age

Nuclear binding of thyroxine (T4) and triiodothyronine (T3) in mononuclear blood cells was investigated in 12 young (age 16-30 years) healthy subjects (group A), in 12 middle-aged (age 31-60 years) healthy subjects (group B) and in 12 elderly (61-90 years) healthy subjects. Serum free T3 was depressed in group C as compared to the younger age groups, whereas serum free T4 and TSH did not differ between the groups. Maximal specific nuclear binding capacity for both T4 and T3 decreased with increasing age, T4 group A: 1.2 fmol T4/100 micrograms DNA, group B: 1.2 fmol T4/100 micrograms DNA, group C: 0.7 fmol T4/100 micrograms DNA; T3 group A: 1.7 fmol T3/100 micrograms DNA, group B: 1.0 fmol T3/100 micrograms DNA, group C: 0.9 fmol T3/100 micrograms DNA. The equilibrium association constant (Ka) for T4 increased with age, group A: Ka = 3.3 X 10(9) l/mol, group B: Ka = 3.2 X 10(9) l/mol, group C: Ka = 6.4 X 10(9) l/mol, whereas Ka for nuclear binding of T3 decreased with age group A: Ka = 3.9 X 10(9) l/mol, group B: Ka = 5.9 X 10(9) l/mol, group C: Ka = 1.8 X 10(9) l/mol. We conclude that, whereas the opposite variations of nuclear capacity and binding affinity for T4 tend to preserve the nuclear T4 concentration, the nuclear T3 concentration definitely decreases with age. The unaltered serum levels of TSH suggest that the decrease of both serum levels of free T3 and the nuclear T3 concentration might represent physiologically changes in old age.     

Serum prolactin in patients with Laron-type dwarfism: effect of insulin-like growth factor I.

Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.     

Determination of human thrombin-antithrombin III complex by enzyme immunoassay

We have developed a specific and sensitive ELISA for the measurement of the TAT in human plasma. The assay follows the sandwich principle and uses two different antibodies directed against human thrombin and human antithrombin III, respectively. The anti-thrombin antibody population used for coating was purified by immunoadsorption on immobilized prothrombin and thrombin, respectively. Antithrombin III antibodies were conjugated with peroxidase. Plasma samples containing TAT were incubated in polystyrene tubes coated with anti-thrombin antibodies; after washing, peroxidase-conjugated antithrombin III antibodies were added and bound enzyme activity was subsequently measured using o-phenylenediamine. The assay was calibrated with definite concentrations (2.0 to 60 micrograms/l) of preformed purified TAT added to TAT-poor plasma. Plots of absorbance at 492 nm against TAT concentrations revealed a linear correlation (r = 0.98). A reference range from 0.85 to 3.0 micrograms/l was calculated from TAT concentration in plasma samples from 88 healthy donors (mean value +/- SD: 1.45 +/- 0.4 micrograms/l). In patients with deep vein thrombosis confirmed by phlebography (n = 15), TAT was found up to 7-13 micrograms/l. Patients with septicemia associated with a consumption coagulopathy (n = 10) showed markedly increased TAT values (greater than or equal to 10 micrograms/l). From these data it can be concluded that measurement of TAT might be a parameter for detection of a latent clotting pathway activation.     

Evaluation of mercury level in waters, bottom sediments and soils in selected rural areas

The studies carried out aimed at evaluation of the mercury level in waters, bottom sediments and soils in selected rural areas, during the season of mercury biocides application and after their withdrawal from agricultural use. Generally, in the period between 1976-1980 the mercury level in 1268 environmental samples has been examined. Shallow dug wells of bad technical state and wrong location particularly exposed to contamination, have been selected for the studies. Mercury level has been determined after mineralization with concentrated acids by means of flameless method of atomic absorption spectrophotometry. The results have been compared with standards for mercury level in drinking waters (1 microgram/l) and in surface waters (5 micrograms/l), with the Warren-Devault criterion for soils (0.25 mg/kg) and with the value 1 mg/kg adopted as maximum natural mercury level in bottom sediments. The results have also been the subject to statistical analysis by means of the Tsao-Fei method and t-test. Mercury level in well waters, surface waters, bottom sediments and soils varied according to the region and the year of study and were respectively: 0.08-26.00 micrograms/l; 0.00-25.20 micrograms/l; 0.02-91.91 mg/kg; 0.01-24.94 mg/kg. Mercury levels of several dozen micrograms/l (waters) and several dozen mg/kg (bottom sediments and soils) have been recorded only in a few cases. A statistically significant decrease of mercury level in the environment of the regions investigated coincided with mercury biocides withdrawal from agricultural practice in our country.     

The effect of cyproheptadine on plasma growth hormone (GH) and on somatostatin response to GH-releasing hormone in man

Cyproheptadine (CPH)--a putative serotonin antagonist--is known to inhibit growth hormone (GH) response to various pharmacological stimuli, as well as during sleep. To elucidate the possible site at which this drug takes effect, we examined plasma GH and somatostatin response to i.v. GHRH1-44 (1 microgram/kg body wt.) before and after CPH treatment in 10 healthy volunteers. The oral administration of CPH (8-12 mg daily for 5 days; total dose 56 mg) significantly curbed GH response to GHRH as expressed in peak plasma GH values (32.0 +/- 6.1 micrograms/l vs. 12.6 +/- 3.2 micrograms/l; P less than 0.01) and in integrated GH response area (2368 +/- 517 micrograms x l-1 x 2 h vs. 744 +/- 172 micrograms x l-1 x 2 h; P less than 0.01). Plasma somatostatin levels did not change in response to GHRH.     

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.     

The effect of various ambient ammonia concentrations on the nitrogen metabolism of carp fry (Cyprinus carpio L.)

Authors studied how 125, 375 and 625 micrograms/l amounts of NH4Cl added to the water influenced the ammonia excretion of carp fry with an average weight of 2.4 g, compared to the control. During the course of the experiments the NH4N concentration, the pH and the temperature were measured for three days, twice daily. On the basis of our results the threshold concentration exerting harmful effects on the ammonia household of carp fry (disturbing the normal rate of metabolism in the fishes and decreasing their growth rate) is between 125 and 375 micrograms/l. NH4H (50-100 micrograms/l NH3). The ammonia concentrations exceeding 375 micrograms/l NH4+ (and 100 micrograms/l NH3, respectively) can be regarded as undesirable and harmful in frybreeding fish ponds. With regard to the ambient ammonia, a daily cycle developed in the excretion of ammonia: contrary to the control, a minimum in ammonia excretion was measured in the morning, while a maximum was measured in the afternoon.     

Binding of insulin-like growth factor-I (IGF-I) to primary cultures of chondrocytes from rat rib growth cartilage

Binding of insulin-like growth factor I (IGF-I) to cultured resting, proliferative and hypertrophic growth plate chondrocytes was investigated. The optimal binding conditions and the extent of degradation of the 125I-IGF-I at 20 degrees C were analyzed in a time-course study. The maximal binding without noticeable degradation was observed after 3 h. The binding of IGF-I to the proliferative cells was 2-fold higher than to the resting and the hypertrophic cells. On the proliferative chondrocytes two classes of receptors with different affinities were found. 125I-IGF-I could be displaced from the proliferative cells by unlabelled IGF-I, IGF-II and insulin, respectively. Half maximal binding was observed at 0.3 nmol/l (= 2.2 micrograms/l) of IGF-I, 4.3 nmol/l (= 32 micrograms/l) of IGF-II and 350 nmol/l (= 2000 micrograms/l) of insulin. No specific binding of human growth hormone (hGH) could be demonstrated. When binding of epidermal growth factor (EGF) to the proliferative cells was assessed, little, but specific binding was observed.     

Growth hormone-releasing hormone and somatostatin in normal and tumoral human pituitaries.

In order to further understand the role of endogenous pituitary neuropeptides in pituitary hormonal content and secretion, GHRH, SRIH and GH contents were quantified in GH adenomas obtained from acromegalic patients with plasma GH levels either high (greater than 5 micrograms/l, range 11 to 550 micrograms/l, n = 11) or in the normal range (less than 5 micrograms/l, range 1 to 3.3 micrograms/l, n = 4). Values were compared to those found in normal human pituitaries. No relationship was found between GHRH content and plasma GH or between SRIH and GH content when considering together adenomas and normal pituitaries. Results showed that there is a positive relationship between GHRH and GH content: when GHRH content is high, GH content is also high (normal pituitaries and GH adenomas of acromegalic patients with high plasma GH) and when GHRH content is low, GH content is also low (GH adenomas of acromegalic patients with plasma GH in the normal range). Conversely, SRIH content is negatively related to plasma GH levels: when SRIH is present, plasma GH is in the normal range; when SRIH is undetectable, plasma GH is high.     

Effect of parathyroid function on serum bone Gla protein

The serum bone Gla protein (BGP) level was measured in patients with idiopathic hypoparathyroidism, and primary hyperparathyroidism, and normal volunteers. The mean serum BGP level was 4.5 +/- 0.20 micrograms/l in 40 normal volunteers. It was significantly lower in 12 patients with idiopathic hypoparathyroidism (1.6 +/- 0.21 micrograms/l, p less than 0.001) and significantly higher in 33 patients with primary hyperparathyroidism (13.0 +/- 1.3 micrograms/l, p less than 0.001). When a single intravenous injection of 30 micrograms of human PTH 1-34 was administered to the patients with idiopathic hypoparathyroidism, there was no significant change in serum BGP within the next 24 hours. Following a therapeutic oral dose of alfacalcidol, serum BGP was appreciably increased (p less than 0.001) from the preadministration value of 1.6 +/- 0.21 micrograms/l to 3.9 +/- 0.34 micrograms/l. In patients with primary hyperparathyroidism, the surgical excision of parathyroid adenoma led to a sharp decrease in serum PTH but a gradual decrease in serum BGP. The latter approximately paralleled the decline in serum alkaline phosphatase. Thus, serum BGP is a marker that reflects bone turnover status in parathyroid disease. It appears that the active form of vitamin D directly increases the secretion of BGP in existing osteoblasts and PTH mainly affects serum BGP to stimulate the bone remodeling cycles with its long term effect.     

The capacity to increase GH secretion at puberty reflects the severity of GH deficiency.

This study evaluates the effect of the spontaneous pubertal increase in sex steroids on GH secretion in GH-deficient patients. Fifteen patients (10 boys, 5 girls) with idiopathic isolated GH deficiency diagnosed before puberty (GH peak < 8 micrograms/l after 2 arginine insulin stimulation tests) were reevaluated for their GH secretion using the same test after completion of their hGH therapy and puberty. Their ages at diagnosis and at the last evaluation were 8.2 +/- 0.7 (SE) (range 4.9-14.9) and 17.8 +/- 0.3 years (15-23), respectively. The data at diagnosis and at last evaluation showed that (1) the mean height increased from -4 +/- 0.3 to -2.5 +/- 0.3 SD (p < 0.01), (2) the mean GH peak increased from 4.4 +/- 0.3 (1.6-8) to 7.6 +/- 0.8 micrograms/l (2-13.2, p < 0.01); at the last evaluation, 8/15 patients had GH peak > 8 micrograms/l and (3) the mean plasma insulin-like growth factor I increased from 0.28 +/- 0.05 to 0.42 +/- 0.03 U/ml (n = 6, p < 0.05). The mean increase in the GH peak was 3.2 micrograms/l (-3 to 10.6). It was negatively correlated with the degree of growth retardation at diagnosis (r = -0.74, p < 0.005). We conclude that the increase in the GH peak at puberty in patients with GH deficiency reflects the severity of GH deficiency and that a corrective factor of the cutoff number is necessary for the diagnosis of GH deficiency in puberty.     

Hyaluronate and type III procollagen peptide concentrations in bronchoalveolar lavage fluid as markers of disease activity in farmer's lung.

Ten patients were studied during an acute episode of farmer''s lung. Prominent findings were an impaired diffusion capacity (on average only 51% of predicted) and substantially increased amounts of hyaluronate and type III procollagen peptide recovered during bronchoalveolar lavage; mean concentrations of these constituents in lavage fluid were 547 (range 137-1125) and 9.7 (2.8-19.4) micrograms/l, respectively. In bronchoalveolar lavage fluid from healthy controls (n = 21) hyaluronate concentrations were less than 15 micrograms/l and procollagen peptide concentrations less than 0.2 micrograms/l. Lavage fluid concentrations of these potential markers of fibroblast activation declined during the recovery phase of farmer''s lung; four to 10 weeks after admission (n = 7) mean concentrations of hyaluronate and procollagen peptide were 154 (range 38-650) and 4.4 (0.6-15.8) micrograms/l, respectively. At clinical remission six to 14 months after admission concentrations of these markers had returned almost to normal, though slightly increased concentrations were still evident in about half the patients (n = 7). At that time lung volumes were normal but diffusion capacity remained slightly subnormal. It was concluded that in farmer''s lung release of hyaluronate and type III procollagen peptide reflects activity of the disease. Increased synthesis of these connective tissue components continuing in a patient avoiding mouldy plant material may signal an increased risk of developing fibrotic lung disease. The abnormal accumulation of hyaluronate in the smaller airways in acute farmer''s lung may be expected to immobilize water and thereby provide a possible mechanism of the interstitial inflammatory lung oedema with associated impaired gas diffusion. This hypothesis is supported by the relation found between hyaluronate in lavage fluid and reduced diffusion capacity.     

Heterotrophic microbial activity and organic matter degradation in coastal lagoons of Colombia

In this study we measured the community respiration and the bacterial respiration as part of the overall degradation process of organic material. Additionally, the turnover rates of the pools of dissolved free glucose and acetate as representatives of the fraction of easily degradable low molecular organic solutes were determined. The study was performed in several coastal lagoons of the "Outer Delta of the Río Magdalena" in northern Colombia. The lagoons can be separated into two groups: The first group contains highly productive brackish lagoons with chl a concentrations ranging from 62-130 micrograms/l. The second group consists of less productive freshwater lagoons with chl a between 5.5-19 micrograms/l. Turnover rates of glucose and acetate were very fast in the highly productive lagoons resulting in turnover times of less than 20 min for both compounds. In the less productive systems the cycling of glucose and acetate was much slower. Here the mean values of the turnover times were 2 hr for glucose and 1.5 hr for acetate. The rates of bacterial DNA-formation measured as thymidine incorporation differed significantly between both groups of lagoons, being very high (1.86-2.76 nmol/l/hr) in the highly productive and relatively low (0.073-0.55 nmol/l/hr) in the less productive group. Water column community respiration ranged between 122 and 16 micrograms C/l/hr with means of 88 micrograms C/l/hr in the highly and 19 micrograms C/l/hr in the less productive group. In the first group the mean values of the bacterial contribution to community respiration amounted to 37% and in the second group to 18%. The bacterial respiration was determined in an indirect way via bacterial biomass production and assuming a growth efficiency of 50%. It is discussed whether this relatively high growth efficiency allows reasonable results in both groups of lagoons.     

Solid phase immunoradiometric assay for porcine serum ferritin

1. A solid phase immunoradiometric assay using anti-serum coated polystyrene tubes, is described for the assay of porcine serum ferritin. 2. The mean concentration of ferritin in the serum of both male and female pigs (Sus scrofa) was 12.1 micrograms/l +/- 8.7 micrograms (range less than 1-35 micrograms/l) and no sex differences were observed in 40 pigs from 1 day to 4 years old. 3. Serum ferritin increased with increasing body iron stores in iron loaded pigs as assessed by hepatic iron concentration. 4. The assay is sensitive (detecting less than 1 microgram/l), reproducible, specific and it does not cross-react with human or rat ferritin.     

Chronic exposure of coho salmon to sublethal concentrations of copper--II. Distribution of copper between high- and low-molecular-weight proteins in liver cytosol and the possible role of metallothionein in detoxification

1. Liver cytosol samples from juvenile coho salmon exposed over a 14-week period to 70 micrograms/l (1/4 LC50) or 140 micrograms/l (1/2 LC50), were separated into high-molecular-weight and low-molecular-weight fractions by column chromatography on Sephadex G-75, and compared to similar samples obtained from control fish. 2. The levels of copper in the low-molecular-weight function of fish exposed to 70 micrograms/l were not significantly increased over control values for the first 6 weeks but then increased rapidly, while those of fish exposed to 140 micrograms/l increased substantially in the first 2-4 weeks of exposure, then levelled off. 3. In the exposed fish the levels of copper in the high-molecular-weight fraction were not significantly elevated above control levels over the first 8-10 weeks but then increased significantly. 4. The low-molecular-weight fractions of exposed fish were shown to contain increasing levels of metallothionein. The metallothionein was isolated on DEAE-cellulose and characterized by amino acid analyses.     

Optimization of the medium for the yeast synthesis of biotin

In order to increase the yield of biotin produced by the culture Sporobolomyces pararoseus, the medium containing sucrose, asparagine, MgSO4 (NH4)2SO4, KH2PO4, vitamin complex and trace elements was optimized. With the aid of a fractional factor experiment (2(5-1)) and a complete factor experiment (2(4)), the proportion of constituents was chosen in such a way as to double biotin yield, i.e. to increase it to 55.25 micrograms/l. An enrichment of the medium with yeast autolysate, casein hydrolysate and peptone in the presence of adenine increased biotin yield to 105.7 micrograms/l and cell productivity from 6.1 to 8.0 micrograms/l dry biomass.     

Insulin-like growth factor binding protein 1 (IGFBP-1) levels in Turner syndrome.

We tested whether IGFBP-1, a modulator of IGF-I action, would play a role in the pathogenesis of growth failure and metabolic picture of Turner syndrome. Fasting serum levels of IGFBP-1 were assessed in nineteen girls with Turner syndrome (aging 6.5 to 17.2 years) by radioimmunoassay. Our patients showed normal values of IGFBP-1 (mean +/- SD: 68.6 +/- 32.5 micrograms/l, range: 16 to 134 micrograms/l; range for age and pubertal stage-matched normal children: 15 to 180 micrograms/l). IGFBP-1 levels inversely correlated with bone age (p < 0.05), weight (p < 0.001), percentage of ideal body weight (p < 0.002) and body mass index (BMI) (p < 0.001). Our results seem to rule out a role of IGFBP-1 in the pathogenesis of growth failure in Turner syndrome. The close inverse relationship between IGFBP-1 levels and BMI suggests the serum concentrations of IGFBP-1 to be regulated by the nutritional status. Due to IGFBP-1 inhibiting action on IGF biological activity, the reduction of IGFBP-1 levels in overweight subjects might represent a mechanism to enhance the IGF insulin-like activity, thus supplementing the insulin action.