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Biomedical subjects

A Barreca

Publications and source records attributed to A Barreca.

At least 91 records · Page 5Linked to original sources

Long-lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients.

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition.

Acromegaly↗

Partial characterization of somatomedin C-like immunoreactivity secreted by breast cancer cells in vitro.

The in vitro secretion of immunoreactive somatomedin C/insulin-like growth factor I (IR Sm-C/IGF-I) by two human breast cancer cell lines, MCF-7 and EVSA-T has been studied. IR Sm-C/IGF-I concentration showed a linear increase in serum-free culture media over 72 h of incubation for both cell lines, and a close correlation with cell number (P less than 0.001). To characterize this immunoreactivity, a pool of conditioned media collected after 72 h of incubation was dialyzed overnight against 1 M acetic acid, lyophilized, and gel filtered on a Sephadex G-50 column. Fractions were determined for Sm-C/IGF-I content and for the presence of a specific carrier for Sm-C/IGF-I. Two peaks of Sm-C/IGF-I-like immunoreactivity were evidenced, the first in the high molecular weight region and the second corresponding to the molecular weight of the free peptide. The first peak evidenced also a specific binding ability for radioiodinated Sm-C/IGF-I, suggesting that the activity found in this region could be interpreted as interference of the specific free binding sites in the immunoassay. Analysis of this peak by polyacrylamide gel electrophoresis demonstrated the presence of a specific binding for Sm-C/IGF-I in a molecular weight range between 35,000 and 45,000 Da, which was not modified in reducing conditions. The binding activity was competitively inhibited by addition of cold Sm-C/IGF-I but not by insulin excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Body composition after 'very-little-stomach' biliopancreatic bypass.

The nutritional status prior to and 3 months and 1 year after biliopancreatic bypass surgery was evaluated. The common nutritional indexes (serum albumin and transferin concentrations, daily urinary creatinine excretion and delayed hypersensitivity) were determined. The body compartments were derived from total body water (TBW) and total body sodium (TBNa), measured by dilutional technique, and total body potassium (TBK), calculated from TBW, TBNa, and the ratio of the sodium plus potassium content divided by the water content in a sample of whole blood. Before surgery, obese patients showed a dilatation of both fat an lean compartments with a normal lean body mass (LBM) qualitative composition, as indicated by TBNa/TBW, and TBNa/TBK ratios not greater than those measured in controls. Three months following very-little-stomach biliopancreatic bypass (VLS BPB), a consistent reduction of body weight and body fat were observed. The body cell mass value fell and reached a level closely similar to that found in lean control subjects. LBM showed only a slight decrease. A sharp increase of TBNa/TBW and TBNa/TBK ratios demonstrated a dilatation of the extracellular space. This malnutritional status was not detected by the usual nutritional parameters. One year after VLS BPB surgery, the patients' body composition became very similar to that of lean subjects, though a TBNa greater than that of controls suggested that a slightly expanded extracellular space was still present.

Adult↗

Role of aging on growth hormone and prolactin release after growth hormone-releasing hormone and domperidone in man.

Growth hormone (GH) and prolactin (PRL) secretion after GH-releasing hormone (GHRH) and domperidone (DOM), an antidopaminergic drug which does not cross the blood-brain barrier (BBB), was evaluated in 8 healthy elderly men (65-91 years) and in 7 young adults (23-40 years). All received in random order at 2-day intervals: GHRH(1-40) (50 micrograms i.v.) bolus, DOM (5 mg/h) infusion, GHRH(1-40) (50 micrograms i.v.) plus DOM (5 mg/h i.v.), saline solution. In elderly men GH increase after GHRH was significantly lower than in young men. DOM alone did not change GH secretion in either of these groups, whereas it increased the GH response to GHRH only in young adults. PRL levels increased in both young and elderly men during both DOM and GHRH plus DOM, but the PRL release was more marked in young than in elderly men. Both integrated secretion of GH after GHRH and of PRL after DOM were inversely correlated to chronological age. Our data show an impairment of GH rise after GHRH and of PRL after DOM in elderly adults. It is also stressed that peripheral blockade of dopamine receptors by DOM is unable to amplify the GH response to GHRH only in elderly men. A reduction in GH release after GHRH might be related to aging, perhaps through a reduction of dopaminergic tonus.

Adult↗

A clinical study of the pineal gland activity in oncologic patients.

It has been known for many years that the pineal gland is involved in regulating tumor growth. In order to evaluate the functional activity of the pineal gland in neoplastic diseases, melatonin serum levels and its light/dark rhythm have been determined with the RIA method in patients affected by various forms of tumor. Irrespectively of the type of the tumor and of its localization, existence of two subpopulations has been observed within the oncologic patients, the former with normal levels of melatonin, and the latter with high ones. The light/dark rhythm of melatonin was anomalous in some cases. An evident decrease of serum melatonin values was seen after chemotherapy. It might be interesting to establish whether melatonin levels may conditionate the prognosis of patients with cancer.

Adolescent↗

Growth hormone and somatomedin-C response to synthetic human pancreatic tumor GH-releasing factor in hypopituitary and constitutionally short children.

GH and somatomedin-C response to acute hpGRF-44 iv administration (1 microgram/Kg bw) was studied in 16 patients with hypopituitarism (GHD) and in 7 constitutionally short subjects. GH-deficient patients evidenced a significant GH increase peaking between 15 and 60 min. (4.95 +/- 0.88 ng/ml, mean +/- SE) (p less than 0.01 vs placebo). In non GH-deficient subjects GH increase was more pronounced (peak 18.00 +/- 3.01 ng/ml; p less than 0.01 vs both placebo and GHD group). Acid-extractable somatomedin-C was slightly, but significantly higher than baseline at 12th h (p less than 0.01) in both patients with hypopituitarism (basal value: 0.067 +/- 0.021 U/ml; 12 h: 0.096 +/- 0.024 U/ml) and constitutionally short subjects (basal value 0.62 +/- 0.13; 12h 0.72 +/- 0.16 U/ml). In 3 subjects with hypopituitarism multiple iv administrations (1 microgram/kg bw at 09:30 and 21:30 h for 4 days) produced on the average a modest increase of the GH responsiveness, were more effective to enhance somatomedin-C concentration, but not sufficient to reach normal levels. Sc administration of the same dose at 4-h intervals by a programmable portable pump - performed on 6 GHD subjects - produced an increase of GH peak response on the 4th day of treatment (1.38 +/- 0.31 ng/ml) with respect to the one observed on the first day (0.42 +/- 0.09 ng/ml). Somatomedin-C increase was low and inconstant. These data support the use of a 4-5-day pulsatile treatment in the differentiation between hypothalamic and pituitary deficiency, and the possibility of therapeutical use of GRF with the same protocol when a response is evidenced.

Adolescent↗

Partial purification and characterization of a neutral insulin-like growth factor. Biochemical and biological properties.

A peptide with an isoelectric point of 6.5-7.0 was purified from Cohn fraction IV on the basis of its capacity to cross react with labelled insulin to human placental cell membrane receptors. It possesses insulin-like activity in the adipocyte bioassay (30 mU insulin equivalent/mg of protein) which is in the same order as its activity in the insulin radioreceptorassay (25.5 mU/mg). Somatomedin bioactivity is 40 U/mg in the porcine cartilage assay. In contrast, although in quiescent human fibroblast this peptide preparation has 6% of the mitogenic potency of somatomedin-C/insulin-like growth factor I on a weight basis, cross-reactivity in radioimmunoassay for somatomedin-C/insulin-like growth factor I, insulin-like growth factor II and insulin are very low. It is concluded that this peptide, although exhibiting the major biological characteristics of an insulin-like growth factor is different from the hitherto described somatomedins.

Adipose Tissue↗

Evidence for an increased somatomedin-C/insulin-like growth factor I content in primary human lung tumors.

Immunoreactive somatomedin-C/insulin-like growth factor I (SM-C/IGF I) content was measured in human neoplastic lung tissue obtained from surgery on 10 patients (seven epidermoid carcinoma, three adenocarcinoma), and in normal lung tissue obtained from the same excised portion. SM-C/IGF I content in lung tumors was 615 +/- 123 (SE) milliunits/g of tissue (range, 214-1531), significantly higher (P less than 0.01) than normal tissue (234 +/- 51 milliunits/g of tissue; range, 37-537); in particular, every subject showed a clear-cut difference of SM-C/IGF I content between neoplastic and normal tissue (ratio, 3.41 +/- 0.69; range, 1.4-7.2). The results were essentially unchanged when data were expressed relative to hemoglobin or DNA tissue content. By contrast, in peripheral plasma SM-C/IGF I concentration was 0.51 +/- 0.17 units/ml, significantly lower (P less than 0.01) than in 59- to 70-yr-old control subjects (1.10 +/- 0.13 units/ml). In conclusion, the lung tumors studied, irrespective of their histological structure, contain more SM-C/IGF I than does normal tissue. Whether this is due to a primary in situ production of SM-C/IGF I or is secondary to overproduction of other inducers such as platelet derived growth factor-like peptides is yet to be clarified. The reduced circulating SM-C/IGF I concentration seems to be related more to the nutritional status of the patients.

Aged↗

[Evaluation of body composition in obese subjects].

The body composition of 12 obese patients was assessed. The dilution method was used to assess the total areas of sodium and water. Total potassium was measured indirectly using the following formula: total potassium = R X total body water-total body sodium, where R represents the contents in a whole blood sample. Both fat and muscle mass were found to be increased in the obese subjects. Examination of the total sodium/total water ratio and the relationship between weight and muscle mass, cellular mass and total fat showed the dimensional increase was harmonious.

Adipose Tissue↗

Prolactin secretion in pubertal and adult male subjects.

Prolactin, LH and FSH circadian secretion were studied in a group of 20 boys in various pubertal stages and in 13 normal male adults. Prolactin 24-hour integrated concentration was similar in all groups except in stage 2 boys, in which it was significantly higher with respect to stage 3-4 boys. This pattern was observed also for nocturnal, but not for diurnal concentration. As already described by other authors, LH showed and amplified circadian secretion in stage 2 and 3-4 boys, particularly during night time. FSH increase was less evident, and reached the peak 24-hour mean concentration in stage 2 subjects. Our results suggest that during puberty the hypothalamic pituitary system increases its activity not only with regard to gonadotropins but also to prolactin secretion.

Adolescent↗

In vivo and in vitro effect of liver on somatomedin generation.

The serum concentration of circulating somatomedins was measured in the blood of healthy donors and subjects with hepatic cirrhosis, and in culture media from in vitro explants of healthy and cirrhotic human liver. Serum levels of somatomedin bioactivity were significantly lower in cirrhotic subjects (0.42 +/- 0.03 U/ml; M +/- SEM) compared with age matched controls (0.99 +/- 0.03 U/ml). Radioreceptor assay of somatomedin concentrations confirmed this reduction in cirrhotic patients (0.89 +/- 0.06 U/ml) compared with controls (1.32 +/- 0.05 U/ml). A parallel reduction in somatomedin circulating binding ability was also observed (99.43 +/- 7.28% in cirrhotic and 123.5% +/- 10.8% in normal subjects). In vitro explants from normal human liver tissue produced a significant increase (0.57 +/- 0.09 U/ml) in somatomedin bioactivity contained in the medium (0.29 +/- 0.06 U/ml), while a decreased bioactivity (0.12 +/- 0.06 U/ml) was observed with explants of cirrhotic livers. These results support a role of liver in the biosynthesis of both somatomedin and somatomedin binding protein.

Adult↗

Growth hormone secretion in pubertal and adult subjects.

GH responsiveness to insulin-induced hypoglycaemia and its circadian secretion were studied in a group of subjects in different pubertal stages. The GH peak after insulin was minimal in stage 1 boys (7.6 +/- 1.3 (SEM) ng/ml) and increased progressively, in parallel with pubertal maturation, reaching a maximum in the adult state (20 +/- 4.0 ng/ml); the basal value was superimposable in all groups studied. The circadian secretion showed a sleep-related surge which was almost identical in the different stages; however in pubertal stage 1 boys multiple secretory peaks were observed, mainly during waking hours. A statistically significant difference (P less than 0.05) was observed in the mean concentration recorded during the day with a maximum in stage 1 boys (2.7 +/- 0.2 ng/ml) and a gradual decrease to a minimum in adults (1.2 +/- 0.3 ng/ml). This pattern seems to suggest that pulsatile rhythm is present in boys, similar to that observed for gonadotrophins.

Adolescent↗

Growth hormone bioactivity and immunoactivity in tall children.

In subjects with constitutional tall stature, both low and high GH response to stimulation tests have been observed when measured by commercial kits. To investigate the reason for these conflicting results, we evaluated growth hormone (GH) secretion using different assays as well as GH-binding protein and insulin-like growth factor-I (IGF-I) concentrations in tall children. Serum samples were collected from 22 prepubertal constitutionally tall children, aged 2.87-13.25 years, during two pharmacological tests to evaluate serum GH levels measured by both immunofluorometric assay (IFMA) and the Nb2 cell bioassay. Serum IGF-I values were evaluated by RIA. Circulating low affinity (LA) and high affinity (HA) GH-binding proteins (GHBPs) were evaluated by FPLC gel filtration. Considering the highest serum GH levels as measured by IFMA, the 22 tall subjects were divided into two groups: group A including 16 children with blunted serum GH peak levels (5.78+/-0.68 ng/ml) and group B including 6 subjects with normal serum GH peak values (15.73+/-1.56 ng/ml). No differences were observed in serum GH peak levels as measured by the Nb2 cell bioassay between group A (14.77+/-1.54 ng/ml) and group B (16.03+/-1.96 ng/ml), and between both groups and 11 age-and sex-matched controls (12.25+/-1.19 ng/ml). In group A, the Nb2 cell bioassay/IFMA ratio of serum GH peak levels (0.29+/-0.08) was significantly higher (p<0.05) than in group B (0.07+/-0.01). No differences were found in serum LA-GHBP and HA-GHBP as well as in IGF-I concentrations between the 16 patients of group A and the 6 of group B. Likewise, no difference in auxological parameters was found between the two groups. The biological activity of GH evaluated using the Nb2 cell bioassay is similar in tall children with a low GH response as measured by IFMA in comparison with those with a normal GH response, and is in agreement with both the auxological data and serum IGF-I concentrations.

Adolescent↗

Spontaneous growth hormone and somatomedin-C/insulin-like growth factor-I secretion in obese subjects during puberty.

It has been reported that adult obese subjects present a reduced growth hormone secretion. As no data are available in the pubertal period, which is characterized in lean subjects by an increased spontaneous growth hormone secretion, the growth hormone circadian concentration was studied in a group of 18 obese male subjects in different pubertal stages, and compared to 26 age-matched control subjects. The data observed evidenced no statistically relevant differences regarding LH and FSH circadian secretion and morning testosterone concentration. On the contrary a statistically significant (p less than 0.02) difference in growth hormone 24 h integrated concentration was evident, particularly in prepubertal subjects; the sleep-related peak was evident in 28% of obese subjects and in 85% of controls. Sm-C/IGF-I concentration was similar to the concentration observed in controls in the prepubertal stage, but did not show the expected increase in the late puberty. Auxological data, performed on a sample of 80 subjects, showed both advanced height and bone age at beginning of puberty, and a trend toward a reduction of percentile for height in parallel with the pubertal maturation, suggesting that pubertal growth spurt in obese subjects is at least less pronounced than in lean subjects. It is concluded that GH and Sm-C/IGF-I secretion is impaired during puberty in obese subjects, leading to a reduced growth rate, while in the prepubertal period factors other than GH may replace or even potentiate its action.

Adolescent↗

Study of bioassayable somatomedin on renal artery and vein.

Somatomedin was measured by rat bioassay in samples obtained from renal artery and vein, in order to study the role of this organ in the production of somatomedin activity. The results showed a significant difference, with an increase of the activity in the venous samples. According to the data reported in the literature with bioassay (low values) and radioreceptor assay (normal or high values) in nephropathic subjects, our results seem to suggest that the kidney mainly inactivates a specific somatomedin inhibitor.

Adolescent↗

Insulin-like growth factor-I in human malnutrition: relationship with some body composition and nutritional parameters.

The insulin-like growth factor-I (IGF-I) plasma concentration was evaluated as a nutritional parameter in 18 patients affected with chronic malnutrition secondary to biliopancreatic bypass and compared with albumin, transferrin, and with body composition parameters: total body water (TBW), total body sodium (TBNa), total body potassium (TBK). Subjects were studied in malnutritional conditions and after 20 to 30 days of parenteral and enteral refeeding treatment. Immunoreactive IGF-I concentration was 0.35 U/ml +/- 0.07 (mean +/- SEM), significantly lower (p less than 0.01) than in age-matched controls (1.14 +/- 0.07 U/ml, n = 29) and rose significantly (0.84 +/- 0.12 U/ml; p less than 0.01) in parallel with the improvement of nutritional status. The ratios TBNa/TBW, TBNa/TBK, and TBK/TBW were then considered as reference parameters for definition of malnutritional state, and compared with IGF-I as well as with the most commonly used parameters, albumin and transferrin. Before treatment, IGF-I evidenced higher specificity (true negative ratios 0.63, 0.43, and 0.40 with regard to TBNa/TBW, TBNa/TBK, and TBK/TBW, respectively) than albumin (0.13, 0.14, and 0.10) and transferrin (0 in all cases), and slightly less sensitivity (true positive ratios for IGF-I 0.80, 0.67, and 0.67; always one for albumin and transferrin). Moreover, IGF-I resulted definitely more sensitive in assessing the effectiveness of the refeeding treatment and, on the basis of the likelihood ratio, it appeared a good discriminator of the nutritional status. The data indicate that different nutritional factors regulate IGF-I, albumin, and transferrin, and suggest that IGF-I can be used as a reliable and specific nutritional parameter, complementary to the others currently used.

Adult↗

In vivo cytokinetic effects of recombinant human growth hormone (rhGH) in patients with advanced breast carcinoma.

We have investigated the possibility of inducing a kinetic recruitment of breast cancer cells by the in vivo administration of recombinant human Growth Hormone (rhGH). Twelve patients with advanced breast cancer received rhGH i.m. for 2 days immediately before the first course of chemotherapy. The following biological parameters have been evaluated before and 24 hours after rhGH administration: tumor TLI, tumor IGF-I content, serum IGF-I concentration. The mean tumor TLI values before and after rhGH were 1.3% and 2.6% respectively; median tumor and serum IGF-I levels before rhGH were 4.64 ng/g and 63.5 ng/ml respectively; after the administration of rhGH median tumor IGF-I content was 1.8 and median serum IGF-I level was 112 ng/ml. These data suggest that, in vivo, rhGH stimulates breast cancer cell proliferation; the mitogenic stimulus is likely due to the local production of IGF-I induced by rhGH.

Aged↗