Jan Komorowski

Resistin increases with obesity and atherosclerotic risk factors in patients with myocardial infarction

The objective of the study was to assess the relation of resistin to the anthropometric parameters, metabolic risk factors, and C-reactive protein (CRP) in men with myocardial infarction. Subjects were 40 obese (age, 53.6 +/- 7.39 years; body mass index, > or =30 kg/m2) and 40 lean (age, 54.4 +/- 6.62 years; body mass index, <25 kg/m2) men with first acute myocardial infarction. Waist and hip circumferences, CRP, uric acid, fasting glucose, lipid profile, and blood resistin concentration were measured. In obese patients, triglycerides, fasting glucose, and CRP were significantly higher whereas high-density lipoprotein cholesterol was lower than in lean patients. The range of blood resistin concentration was 6.0 to 70.5 ng/mL: 27.84 +/- 12.15 ng/mL in obese subjects and 17.35 +/- 11.08 ng/mL in lean subjects (P < .0001). Significant positive correlation was revealed between blood resistin concentration and each of the analyzed anthropometric parameter and with fasting glucose, low-density lipoprotein cholesterol, and CRP, whereas negative relation was observed between resistin and high-density lipoprotein cholesterol. As revealed by univariate logistic regression analysis, risk of blood resistin concentration being greater than the median value (19.75 ng/mL) was increased by obesity, high-density lipoprotein cholesterol <40 mg/dL, hypertension, and CRP. In multivariate model, independent variables associated with higher median of resistin were obesity and CRP. Obesity increased 5.5-fold the probability of blood resistin concentration being greater than 19.75 ng/mL, whereas each 1-mg/dL increase in CRP increased this probability by 13%. In patients with acute myocardial infarction, obesity is positively related to blood resistin concentration. Resistin is likely to play a major role in the atherogenesis and its complications, and this action seems to be mostly related to the inflammatory reaction.

Evaluation of the Levels of bFGF, VEGF, sICAM-1, and sVCAM-1 in Serum of Patients with Thyroid Cancer

Tumour growth and development depend on a complex cascade of angiogenic factors. The aim of the study is evaluation of the level of growth factors VEGF and bFGF, and adhesion molecules sICAM-1, sVCAM-1 in the serum of patients with papillary thyroid cancer. The study comprised 35 patients aged 21-68 years (mean age 46+/-14) who had papillary thyroid cancer diagnosed on the basis of thin needle aspiration biopsy, and were qualified for operative treatment. This group comprised 28 women and seven men. The control group was 26 healthy individuals. Serum concentrations of bFGF, VEGF, sICAM-1, and sVCAM-1 were evaluated by the enzyme-linked immunosorbent assay (ELISA) method. We have observed significantly higher mean concentrations of bFGF, VEGF, and sICAM-1 in the serum of patients with thyroid cancer compared with the control group. There was no significant difference between the sVCAM-1 concentrations of the thyroid cancer group and the control group.

Decreased 1-25 Dihydroxyvitamin D3 Concentration in Peripheral Blood Serum of Patients with Thyroid Cancer

BACKGROUND AND AIMS Vitamin D(3), in addition to its role in calcium homeostasis, has been recognized as playing a role in human cancer development. However, little is known about the association between vitamin D status and the development of thyroid cancer. This study aimed to investigate vitamin D metabolism by measuring 25(OH) D(3), 1-25 (OH)(2) D(3), PTH and calcium concentrations in the peripheral blood of patients with different forms of thyroid tumors. METHODS The 25-hydroxyvitamin D(3) ,1-25- dihydoxyvitamin D(3), PTH and calcium serum levels of 50 consecutive patients with epithelial thyroid cancer 27 cases of papillary cancers (PTC), 16 follicular cancers (FTC), and seven cases of anaplastic cancers (ATC) and 34 multinodular nontoxic goiter (MNG) were measured by specific immunoassay. The control group consisted of 26 healthy volunteers. RESULTS Our results revealed significantly lower 1-25 (OH)(2) D(3) concentration in the PTC group (22.67 pg/mL +/- 8.12; p <0.05), FTC group (16.09 pg/mL +/- 6.15; p <0.02) and ATC group (9.48 pg/mL +/- 5.18; p <0.02). Levels of 1-25 (OH)(2) D(3) varied by cancer stage and were also significantly different. A significant decrease in circulating 1-25 (OH)(2) D(3) concentration was found in patients with stage I (24.12 pg/mL +/- 6.77; p <0.05), stage II (16.93 pg/mL +/- 4.55; p <0.05), stage III (12.44 +/- 8.98; p <0.02) and in stage IVa (6.18 +/- 2.22; p <0.01). There were no significant differences when comparing serum levels of 25(OH) D(3), PTH or calcium concentrations among individuals with multinodular goiter, thyroid cancer and age- and sex-matched control volunteers. CONCLUSIONS Our study revealed that impaired vitamin D(3) metabolism may play an important role in thyroid follicular cell oncogenesis.

Hypothalamic-Pituitary-Thyroid Axis and the Immune System

The paper reviews data on bidirectional circuits between the hypothalamic-pituitary-thyroid (HPT) axis and the immune system. The effects of thyroliberin (TRH), thyrotropin (TSH) and of thyroid hormones (thyroxine and triiodothyronine) on the immune system, as well as the effects of mono- and lymphokines on the HPT axis are discussed.

Growth Hormone Replacement Decreases Plasma Levels of Matrix Metalloproteinases (2 and 9) and Vascular Endothelial Growth Factor in Growth Hormone–Deficient Individuals

Background—Matrix metalloproteinases (MMP) are implicated in cardiovascular disease. Growth hormone (GH) deficiency is associated with increased cardiovascular mortality. We assessed whether GH replacement, in GH-deficient adults, has any effect on plasma levels of MMP-2 and MMP-9 and on vascular endothelial growth factor (VEGF), known to activate MMPs. Methods and Results—The study comprised 66 GH-deficient adults, 37.8±14.7 years of age (37 female). Plasma MMP-2 and MMP-9, VEGF, and insulin-like growth factor-1 (IGF-1) were measured at baseline (V1), at 12 months (V2), and at 24 months of GH treatment (V3). IGF-1 levels rose under GH replacement (mean±SD): V1, 151.6±91.9 μg/mL; V2, 270.2 7114.8 μg/mL; and V3, 266.2±109.8 (V1 versus V2; P <0.001: V2 versus V3; P =0.76). MMP-9 exhibited the most pronounced and sustained decline from 1248.0±651.1 ng/mL at V1, 949.2±457.7 ng/mL at V2, and 760.8±386.1 ng/mL at V3 (P <0.001 at all time points). A similar pattern was detected for VEGF levels: 358.5±209.0 pg/mL at V1, 310.6±225.7 pg/mL at V2 (P <0.001), and 283.7±202.7 pg/mL at V3 (V2 versus V3; P =0.005). MMP-2 demonstrated a significant decline initially from V1 to V2 (1134.4±217.8 ng/mL versus 1074.5±203.0 ng/mL, respectively; P =0.031), reaching a plateau at V3 (1072.3±220.2 ng/mL) (V2 versus V3; P =0.93). A negative relation existed between MMP-9 versus IGF-1 and MMP-2 versus IGF-1 (P <0.001 and P =0.007, respectively) as well as between VEGF and IGF-1 (P <0.001). Conclusions—These changes in MMPs and VEGF may contribute to the anticipated reduction in vascular mortality in hypopituitary adults receiving GH replacement.

Systemic blood osteopontin, endostatin, and E-selectin concentrations after vertical banding surgery in severely obese adults.

BACKGROUND Obesity is associated with endothelial dysfunction and increased inflammation as well as with expansion of the capillary bed in regional adipose deposits, and a balance between these factors is involved in angiogenesis. Osteopontin (OPN) is a proinflammatory cytokine involved in regulating immune processes and mediating chronic inflammation. Its level is usually elevated in the plasma and adipose tissue of obese subjects. E-selectin, an adhesion molecule which is released by dysfunctional endothelial cells, is believed to be a marker of an early atherosclerotic process. Endostatin (END), an angiogenesis inhibitor, is present in the blood of obese subjects. The most effective treatment to achieve weight loss in morbidly obese subjects is bariatric surgery. The aim of the study was to evaluate and compare the circulating concentrations of OPN, E-selectin and END as well as the insulin resistance (HOMA-IR) of severely obese patients with metabolic syndrome before and after vertical banded gastroplasty (VBG). MATERIAL AND METHODS The test cohorts comprised eight males and 20 females (total 28 patients) aged from 20 to 59 years with simple obesity and the presence of metabolic syndrome, both before and 3, 6, 12, 24 months after bariatric surgery (six patients were also checked after 36 and four after 48 months). RESULTS Bariatric surgery significantly reduced (over 24 months) body weight, BMI, waist circumference, HOMA-IR and blood concentrations of CRP. Plasma OPN gradually increased after VBG and E-selectin in systemic blood decreased. We did not observe any differences in END concentrations from 12 to 48 months after surgery. CONCLUSION VBG improves metabolic syndrome parameters, decreases E-selectin and gradually increases OST blood concentrations but it does not have any significant influence on END levels.

The evidence of thyroliberin/triiodothyronin control of TSH secretory response from human peripheral blood monocytes cultured in vitro

Immune system function has been shown to be under the influence of various neuromodulators and endocrine system peptides. This in vitro study describes the stimulatory effect of thyrotropin releasing hormone (thyroliberin, TRH) on thyrotropin (TSH) release from cultured human peripheral blood monocytes. The stimulatory effect of TRH on TSH release from monocytes is totally blocked by triiodothyronine (T3) administrations. These results indicate that TSH release from human monocytes is under the control of TRH/T3 mechanisms, similar to hypothalamic-pituitary-thyroid axis.

Increased interleukin-2 levels during standard TRH test in man.

Interleukin-2 (IL-2) is a pluripotential cytokine that, besides its role in the regulation of immunocompetent cells function, also stimulates hormone secretion. On the other hand, several factors, including cytokines (interleukin-1, IL-1; interleukin-6, IL-6) and pituitary hormones (thyrotropin, TSH; prolactin, PRL), exert stimulatory effects on T-cell connected IL-2 production. In order to evaluate the role of both pituitary hormones in the activation of the immune system, the following two standard diagnostic tests were performed: TRH test (0.2 mg) in 8 healthy human subjects (4F/4M) aged 18-50 years, and oral metoclopramide (MCP) test (10 mg) in 8 females with galactorrhea and regular menstruation aged 18-52 years. The mobilization (peak response) of PRL, TSH, triiodothyronine (T3), thyroxin (T4), IL-1 beta, IL-2, IL-6 in TRH test, and PRL, IL-1 beta, IL-2, IL-6 for MCP test were evaluated. The responses of TSH (2.0 +/- 0.3 vs 12.3 +/- 2.2 microlU/ml, p < 0.01), PRL (15.3 +/- 2.3 vs 46.4 +/- 8.8 ng/ml, p < 0.01), T3 (178.0 +/- 16.4 vs 248.7 +/- 21.1 ng/dl, p < 0.001), T4 (7.9 +/- 0.4 vs 9.6 +/- 0.5 micrograms/dl, p < 0.001), and IL-2 (45.6 +/- 7.8 vs 79.9 +/- 16.4 fmol/ml, p < 0.05) in TRH test were noted. The peak response of PRL (16.3 +2- 2.6 vs 107.7 +/- 22.4 ng/ml, p < 0.01) in MCP test was also observed, but without any changes in interleukin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

GH-RH antagonist (MZ-4-71) inhibits VEGF secretion and proliferation of murine endothelial cells.

Angiogenesis plays a key role in solid tumor formation, invasiveness and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is necessary in the process of neovascularisation. Antagonists of growth hormone-releasing hormone (GH-RH) have been shown to suppress both in vivo and in vitro growth and metastasis of many human cancer cell lines. The mechanisms that mediate the antitumorigenic actions of these antagonists involve direct and indirect pathways, but are not completely elucidated. We have examined the effect of GH-RH antagonist MZ-4-71 on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. MZ-4-71 at 10(-8) to 10(-6) M concentrations inhibited the proliferative activity of cultured cells and suppressed the release of VEGF into supernatants of 72 h endothelial cell cultures. To our knowledge this is the first study reporting antiangiogenic properties of GH-RH antagonists.

Effects of Gn-RH, TRH, and CRF administration on plasma leptin levels in lean and obese women.

Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake, increase energy expenditure and influence the function of hypothalamo-pituitary-gonadal, -thyroid, and -adrenal systems. We have examined the association between leptin concentrations (RIA method) and levels of different hormones using standard Gn-RH, TRH and CRF tests (at 0, 30, 60, and 120 min) in regularly menstruating 10 lean and 10 obese premenopausal women in follicular phase. FSH, LH, estradiol (E2) and progesterone (P) concentrations in Gn-RH test; TSH, PRL, fT3, fT4 in TRH test; ACTH, DHEA-S, cortisol in CRF test were measured by RIA, ELISA or IRMA methods. The obese subjects had thicker four skinfolds, higher fat content in the body, and bigger BMI, compared to the lean females. Gn-RH test: We have noted higher basal leptin values in obese women than in lean subjects, which was stable during the Gn-RH test. In the same blood specimen, basal insulin concentrations did not differ between the tested groups of patients. There were no correlations between E(2), P, or gonadotropins and plasma leptin concentrations between both groups of patients. We have revealed the negative correlation between LH mobilization (maximal incremental values over basal levels; Delta%) and baseline leptin concentrations in all observed subjects. TRH test: In both groups of patients the leptin levels decreased at 120 min of TRH administration. We have noted diminished PRL and TSH mobilisation in obese subjects in comparison to the controls. In all females (n = 20) the correlations between TSH or PRL mobilization and BMI, skinfold thickness and the mass of body fat in kg were negative. In obese subjects only we observed the positive correlations between fT(3)concentrations at 60 and 120 min of the test or Delta% of fT(3)and leptin levels. CRF test: In obese females, we noted higher basal ACTH and cortisol concentrations with decreased mobilization (Delta%) of ACTH or cortisol, as compared to the controls. Basal leptin values were also higher in obese women comparing controls and did not significantly change within 2 h after CRF injection. In all the observed subjects (n = 20), we noted positive correlations between baseline values of leptin and ACTH, as well as negative correlation between basal concentrations of leptin and mobilisation of cortisol. The obtained results show that the hypothalamic neuropeptides may influence leptin secretion in humans.