Analysis of Four Circulating Complexes of Insulin-Like Growth Factor Binding Proteins in Human Blood during Aging.

The primary role of insulin-like growth factor binding proteins (IGFBPs) is to regulate availability of IGFs for interacting with receptors, but IGFBPs perform IGF-independent actions as well. The availability and activity of IGFBPs in the circulation is influenced primarily by their concentration and structural modifications, but possibly also by interaction with major plasma proteins such as transferrin, alpha-2-macroglobulin (α2M), and fibrinogen. Four types of circulating IGFBP complexes were examined in this study by immuno- and ligand-binding assays in adults of different age. The amounts of IGFBP-3/transferrin and IGFBP-1/fibrinogen complexes were similar in middle- and old-aged persons, whereas the amounts of IGFBP-1 (or -2)/α2M monomer complexes were lower in the old-aged group and negatively correlated with total IGFBP-1 (or -2) amounts in blood. In contrast to IGFBP-1, IGFBP-2 was present in significantly greater quantities in complexes with α2M dimer than α2M monomer in older individuals. IGFBP complexes did not bind 125I-labeled IGF-I in amounts detectable by ligand blotting. According to the results of this study, the quantities of IGFBP-1 and IGFBP-2, which interact with α2M, are age-dependent and, in the case of complexes with α2M monomer, they are negatively correlated with the total circulating levels of these two IGFBPs.

Association of elevated IGFBP-1 with increased IGF-II concentration in patients with carcinoma of the liver.

Insulin-like growth factors (IGFs) are mitogens for numerous types of cells including cancer cells. The aim of this work was to analyze some of the components of the IGF system to assess which could be potential clinical biomarkers for monitoring patients diagnosed with liver cancer. Compared to healthy persons, patients with liver cancer had a lower concentration of IGF-I and a higher concentration of IGFBP-1, whereas the concentrations of IGF-II and IGFBP-3 remained unchanged. The IGF-I:IGFBP-3 ratio decreased in patients with cancer, while the IGF-II:IGFBP-1 ratio was not altered. Patients with primary carcinoma and those scheduled for surgery had lower IGF-I and higher IGF-II and IGFBP-1 concentrations than patients with secondary carcinoma and those not eligible for surgery. It may be postulated that a liver with primary cancer is induced to increase IGF-II and IGFBP-1 synthesis more than a liver involved in metastatic response. Similarly, in patients eligible for liver surgery an increase in IGF-II may reflect a gradual change in the concentration associated with a different stage of disease. As increased synthesis of certain IGFBPs is necessary to compensate decreased production of the others or increased IGF production, determination of serum IGF-II, IGFBP-1 and their ratio may aid in estimating the compensatory capacity of the liver affected by cancer.

The influence of laparoscopic and open surgery on the concentration and structural modifications of insulin-like growth factor binding protein 3 in the human circulation.

Insulin-like growth factor binding protein 3 (IGFBP-3) is the most abundant insulin-like growth factor binding protein in the circulation. The aim of the present work was to investigate the influence of surgery (laparoscopy and open) on the concentration and carbohydrate content of IGFBP-3. The concentration of IGFBP-3 was measured using an immunoradiometric assay (IRMA), its protein profile was characterised using immunoblotting and its sialic acid content was examined by means of Sambucus nigra agglutinin (SNA) affinity chromatography. The concentration of IGFBP-3 was significantly (p < 0.001) lower in preoperative patients compared with healthy subjects. Only patients that underwent open surgery showed a further significant decrease in the concentration of IGFBP-3. Immunoblotting detected two intact IGFBP-3 isoforms, as well as proteolytic fragments. SNA-affinity chromatography showed that in patients that underwent surgery the ratio between the two IGFBP-3 glycoforms was lower than the ratio in healthy subjects. Patients with gallbladder inflammation that underwent laparoscopy had an increased percentage of specifically bound IGFBP-3 to SNA compared with healthy subjects. Our conclusion is that open surgery decreased the level of IGFBP-3 compared with laparoscopy, whereas patients with gallbladder inflammation that underwent laparoscopy had an increased content of sialic acid in IGFBP-3.

[Cardiovascular manifestations of hyperthyroidism. Clinical significance and preoperative preparation]. / Kardiovaskularne manifestacije hipertireoidizma. Klinicki znacaj i preoperaciona priprema.

More than 200 years ago, Caleb Parry described cardiological manifestations of hyperthyroidism. Interaction of thyroid hormones and sympathoadrenal system (responsible for rhythm disorders) and direct effect of thyroid hormones on the cardiac muscle (responsible for occurrence of hypertrophy and cardiac insufficiency) have been recognized as the pathophysiological basis of cardiovascular disorders of patients with hyperthyroidism. The aim of the study was to retrospectively analyze surgically treated patients with different types of hyperthyreosis, and establish the incidence and clinical significance of the left ventricular dysfunction related to duration and treatment of hyperthyreosis. Evaluation of left ventricular function was based on the ejection fraction during exercise. Signs of hypertrophy were echocardiographically, radiographically and electrocardiographicaly recorded. Over the period 1993-1997 at the Surgical Department of the institute of Endocrinology in Belgrade 423 patients with hyperthyreosis were operated: 293 (69.26%) patients had Graves-Basedow's disease, 74 (17.49%) toxic adenoma, and 58 (13.28%) toxic polynodal struma. The average duration of the disease in patients with Graves-Basedow's hyperthyreosis was 5 yrs, and the average age of patients was 29 yrs; the average duration of hyperthyreosis in patients with toxic adenoma was 1.2 yrs, and in cases of toxic polynodal struma 17 yrs. Pathological response of ejection fraction during exercise was recorded in 60% of patients. Signs of hypertrophy of the left chamber were recorded in 17% of subjects, and insufficiency of the left chamber with congestive stasis in the lungs in 4.6% of patients. The most common ECG changes were: synus tachycardia, higher voltage of P and T waves, elevated amplitude of QRS complex, prolonged P-Q and shortened Q-T intervals. In 20% of cases atrial fibrillation was evidenced. One patient had ECG signs of myocardial infarction. Clinical features of left ventricular dysfunction in hyperthyroidism include: occurrence in younger patients with history of hyperthyroidism, progressive course and occurrence of congestive cardiac failure as well as reversible nature of all cardiac changes after radical therapy of hyperthyreosis which can be medical, surgical or irradiation.

[Results of surgical treatment of primary hyperparathyroidism]. / Rezultati hirurskog lecenja primarnog hiperparatiroidizma.

In the period 1981-1993, 102 patients underwent surgery for primary hyperparathyroidism (HP). Parathyroid adenoma was found in 81, carcinoma in 4 and hyperplasia in 17 patients. HP was usually diagnosed late with marked skeletal or renal damage, psychiatric symptoms and hypertension. Following the first operation in our institution hypercalcemia was successfully reduced in 100 of 102 patients, in two hypercalcemia persisted after the operation and both were reoperated. Postoperative hypocalcemic syndrome (transitory hypoparathyroidism) due to advanced stage of HP and enormous calcium deficit in bones, occurred in 47% of patients (most frequently with skeletal and hypercalcemic form of the disease).

[Occurrence of thyroid gland carcinoma in Graves-Basedow disease]. / Ucestalost karcinoma stitaste zlezde u Graves-Basedowljevoj bolesti.

Among 319 patients with Graves-Basedow disease who were operated upon in surgical department of The Institute of Endocrinology in Belgrade between 1978 and 1990, thyroid carcinoma was found in 15 cases (4.7%). In 10 patients carcinoma was suspected before operation because of the node in diffuse goiter, while in 5 patients carcinoma was found unexpectedly. Tumor was smaller than 1 sm in only one patient. Nine patients had papillary carcinoma, 4 had follicular and 2 had medullary carcinoma. One patient with medullary carcinoma had been treated previously with radioactive iodine. In 2 patients carcinoma was found in recurrent goiter after primary operation, patients with thyroid carcinoma in Graves-Basedow disease were averaging about 10 years older than other patients with Graves-Basedow disease treated surgically.