The NETest liquid biopsy is diagnostic for gastric neuroendocrine tumors: observations on the blood-based identification of microscopic and macroscopic residual diseaseOK.

BACKGROUND: NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease. METHODS: Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or 68Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20). DATA: mean ± SD. RESULTS: Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16. DIAGNOSIS: NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p < 0.0001). In histology-positive, the NETest accuracy was 100% (25/25). Microscopic disease: In image-negative but R1, NETest was elevated in 100% (9/9; 28 ± 9). Levels were elevated vs. controls (7 ± 4, p < 0.0001), or R0 (16 ± 11, p = 0.02). Eight of 21 R0, exhibited positive NETest. Macroscopic disease: Gastric lesions were multiple: 38%, single: 62%, submucosal: 13%, or ulcerated: 13%. Lesions size was ≤5 mm (50%), > 5-9.9 mm (17%), 10-19.9 mm (17%), ≥20 mm (17%) [≥10 mm: 34%). The NETest accuracy was 100% (16/16). Levels (28 ± 7) were higher than controls (7 ± 4, p < 0.0001) or R0 (16 ± 11, p = 0.002) but not to R1 (28 ± 9, p = 0.5). CONCLUSIONS: NETest is diagnostic for gastric NETs. Elevated levels identify both microscopic and macroscopic residual disease. In histology/image-negative disease, elevated NETest may reflect early evidence of increased neuroendocrine gene expression of hypergastrinemia-induced neoplastic transformation of enterochromaffin-like (ECL) cells to tumor status. A sensitive liquid biopsy has utility in the management and surveillance of gastric NET disease.

Serum concentrations of HGF and IL-8 in patients with active Graves' orbitopathy before and after methylprednisolone therapy.

INTRODUCTION: Graves' disease is the most common cause of hyperthyroidism, and orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease. The aims of this study were as follows: (1) to evaluate the serum concentration of HGF and IL-8 in the blood of newly diagnosed Graves' disease patients with the first episode of active GO and healthy controls; (2) to estimate the influence of the thyroid function (euthyreosis vs. hyperthyreosis) on HGF and IL-8 blood levels in patients with active GO; (3) to evaluate the influence of intravenous (i.v.) methylprednisolone (MP) pulse therapy and additional oral MP treatment on HGF and IL-8 blood levels in patients with active GO. PATIENTS AND METHODS: Thirty-nine Graves' disease patients with the first episode of clinically active GO (Group A) were enrolled in the study. To estimate the influence of the thyroid function on serum concentrations of the studied proangiogenic factors, Group A was divided into Group A I (n = 18) in euthyroid and Group A II (n = 21) in hyperthyroid stage of Graves' disease in moderate-to-severe stage of GO. The control group consisted of 20 healthy volunteers age- and sex-matched to the GO group. Concentrations of the studied proangiogenic factors in serum samples were measured by an enzyme-linked immunosorbent assay before (Group A) and after (Group A1) intensive pulse i.v.MP treatment and 1 month after the end of additional oral MP treatment (Group A2). RESULTS: We found a significant increase in serum concentrations of studied factors in the GO group before immunosuppressive therapy when compared with the control group and decrease after i.v.MP treatment. One month after the end of additional oral MP treatment (Group A2), serum concentrations of HGF and IL-8 still decreased and no significant difference was observed in HGF and IL-8 concentrations when compared with the control group. We did not find the difference in serum concentration of the studied proangiogenic factors between patients in euthyroid and hyperthyroid stage of Graves' disease before MP therapy. CONCLUSIONS: Serum HGF and IL-8 concentrations are elevated in Graves' disease patients with active Graves' orbitopathy as compared to the healthy control group. Successful management of active Graves' orbitopathy with glucocorticoids is associated with a decrease in HGF and IL-8 serum concentrations.

Serum concentration of VEGF and PDGF-AA in patients with active thyroid orbitopathy before and after immunosuppressive therapy.

INTRODUCTION: Thyroid orbitopathy (TO) is the most frequent extrathyroid manifestation of Graves' disease. The aim of this study was to evaluate the serum concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth Factor-AA (PDGF-AA) in the blood of patients with active OT before and after immunosuppressive therapy. PATIENTS AND METHODS: The study was performed in group of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I) and hyperthyroid (n=21, Group A II) stage of Graves' disease in moderate or severe stage of TO. Control group consist of 20 healthy age-matched control subjects. Concentration of studied proangiogenic factors in serum samples were measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and after (group A1) intensive pulse methylprednisolone treatment and one month after the end of additional oral methylprednisolone treatment (Group A2). RESULTS: We have found significant increased serum levels of VEGF in patients with TO (reg-ardless to treatment) when compared with control group (542.4±328.1 pg/ml vs. 94.6±55.3 pg/ml, p=0.0002) and increased serum levels of -PDGF-AA in patients before treatment (3 173.6±1 480.3 pg/ml) in comparison with controls (1 768.9±520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2 325.9±1 456.8 pg/ml). One month after the end of additional oral methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased and were was not significant difference with value in control group (1 853.1±795.4 vs. 1 769.9±520.0 pg/ml, p=0.99). Serum concentration of VEGF was still significantly higher compared with control. We have not observed difference in serum concentration of studied proangiogenic factors between patients in euthyroid or hyperthyroid stage of Graves' disease. CONCLUSIONS: RESULTS of the present study confirm the fact that angiogenesis could play a role in pathogenesis of thyroid orbitopathy.

Differential action of two prolactin isoforms on ischemia and re-perfusion-induced arrhythmias in rats in vivo.

BACKGROUND: The different influences of one of the PRL isoforms (PRL I) on the cardiovascular system have been described in the past. AIM: Our goal was to establish an appropriate iv dose of 2 PRL isoforms (PRL I and PRL II) in intact rats. After establishing this dose, PRL I (0.01 mg/kg) or PRL II (0.001 mg/kg) was administered in bolus 10 min before left anterior descending coronary artery occlusion (7 min) followed by re-perfusion (15 min). We then aimed to study and compare the effects of these isoforms on ischemia- and re-perfusion-induced arrhythmias in the ischemia and re-perfusion-induced arrhythmias model in rats. MATERIALS AND METHODS: Mortality index, ventricular fibrillation and tachycardia (VF, VT) incidence and duration, systolic, diastolic, and mean arterial blood pressure, heart rate and myocardial index of oxygen consumption [pressure rate product (PRP)] were measured and calculated. RESULTS: Both PRL isoforms reduced animal mortality (from 50 to 18.75 and 25%, respectively). PRL II significantly reduced VF incidence (to 25%) as well as VT duration (18.21 ± 3.09) and these effects were markedly different from PRL I and from the control group (p<0.05). Both PRL reduced PRP in the recovery phase (p<0.05). CONCLUSIONS: We proved that supraphysiological doses of PRL isoforms administered in bolus could protect against sudden cardiac death as well as severe arrhythmias episodes during re-perfusion. Because of PRL's positive influence on the cardiovascular system and as an endogenous, well-tolerated substance, it might be of potential clinical use.

Serum concentrations of adiponectin and resistin in hyperthyroid Graves' disease patients.

UNLABELLED: This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). CONCLUSIONS: Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.

The effect of various methods of psoriasis treatment on somatotrophin axis hormones in serum.

OBJECTIVE: To investigate the effect of pharmacotherapy and phototherapy on the concentration of hormones of the somatotrophin axis [growth hormone (GH), insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3)] in the serum of patients with psoriasis in exacerbation and remission. METHODS: GH and IGFBP-3 in serum were determined by immunoradiometric assay (IRMA), and IGF-I concentrations - by radioimmunological assay (RIA). The dermatological state was assessed by the psoriasis area and severity index (PASI). RESULTS: There was no significant difference in the GH concentrations in patients both in exacerbation and remission, irrespective of therapy applied. However, in the group treated by phototherapy a significant increase in IGFBP-3 secretion was observed, whereas in the group treated with cyclosporin A - a significant increase in IGF-I secretion was observed in remission. CONCLUSION: Different methods of treatment have different effects on the secretion of somatotrophin axis hormones, but generally the hormone concentrations do not return to the values observed in healthy people. The therapeutic actions of the drugs concerned are not fully known and require further investigations.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71 years (mean age 66.2+/-3.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.88+/-6.23 micromol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8.72+/-3.34 micromol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88+/-220.91 pg/mL) compared with the control group (527.08+/-208.97 pg/mL). Red blood cell folate (158.44+/-56.30 ng/mL) and plasma folate (6.5+/-3.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.86+/-59.33 ng/mL and 7.93+/-5.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

TGF-beta1 mRNA expression in liver biopsy specimens and TGF-beta1 serum levels in patients with chronic hepatitis C before and after antiviral therapy.

BACKGROUND AND OBJECTIVE: Transforming growth factor (TGF)-beta1 is the best-characterized profibrogenic cytokine. TGF-beta1 increases the production of extracellular matrix proteins and their receptors and inhibits the synthesis of matrix degrading proteolytic enzymes. We undertook this study to simultaneously evaluate the effect of interferon alpha 2b plus ribavirin therapy on TGF-beta1 daily serum levels and on mRNA TGF-beta1 expression in liver biopsy specimens from 60 patients with chronic hepatitis C. METHODS: Serum levels of TGF-beta1 were measured by ELISA. The levels of the RNAs in liver biopsy specimens were measured by quantitative reverse transcriptase polymerase chain reaction. After treatment, patients were divided into two groups: 34 responders [undetectable hepatitis C virus (HCV)-RNA, normal ALT levels, decrease in histology activity index compared with pretreatment liver biopsy] and 26 non-responders (detectable HCV-RNA, elevated ALT levels, no decrease in the histology activity index). RESULTS AND DISCUSSION: In patients with hepatitis C, the 'responders' to the antiviral treatment showed significant decreases in both mean daily serum TGF-beta1 levels and mRNA TGF-beta1 expression in the liver biopsy specimens. The 'non-responders' serum TGF-beta1 concentrations did not change significantly, but the mRNA TGF-beta1 expression did. CONCLUSION: Both serum TGF-beta1 concentration and mRNA TGF-beta1 expression in liver biopsy specimens may be useful as prognostic markers in patients with hepatitis C undergoing antiviral therapy.

Changes in lipid metabolism in women with age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss among people aged 65 and older. At present the origin of AMD still remains unknown. The objective was to evaluate the chosen lipid and lipoprotein concentrations in blood of patients with AMD. Sixty women aged 55-71 (mean age 65.1+/-5.7) were treated in the outpatient ophthalmological clinic for more than two years because of AMD. We evaluated total serum cholesterol (TCH), triglycerides (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) by direct spectrophotometry (Human and Randox standard kits, USA). We found a significant increase of TCH, LDL and TG (224.36+/-41.67 mg/dl, 159.02+/-39.66 mg/dl and 120.92+/-42.64 mg/dl), and a significant decrease of HDL (38.68+/-6.36 mg/dl) in the AMD patients when compared with the control group. We have not found a significant difference in the average TG level between the studied groups. The concentration of Apo B was markedly increased (164.66+/-46.46 mg/dl) and Apo AI concentration was markedly decreased (128.9+/-17.01 mg/dl) in the AMD patients when compared with the control group. There was no significant difference in the concentration of the Lp(a) between the two groups. The results of our present study could point to the fact that changes in the lipid metabolism could be one of the very important risk factors involved in the pathogenesis of AMD.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71years (mean age 66.23.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.886.23 micronmol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8,.723,.34 micronmol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88220.91 pg/mL) compared with the control group (527.08208.97 pg/mL). Red blood cell folate (158.4456.30 ng/mL) and plasma folate (6.53.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.8659.33 ng/mL and 7.935.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

Plasma concentration of soluble intercellular adhesion molecule-1 in women with polycystic ovary syndrome.

Soluble intercellular adhesion molecule-1 (sICAM-1) is ranked as one of the endothelial dysfunction markers and factors predicting diseases of the cardiovascular system. The main objective of this study was to assess the serum concentration of sICAM-1 in women with polycystic ovary syndrome (PCOS) and to verify correlations between serum sICAM-1 levels and selected anthropometric, metabolic and hormonal indices. The study assessed 57 women with PCOS (mean age 28.2 +/- 6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI) < or =25 kg/m2 (21 women of mean age 27.4 +/- 7.0 years) and the second with BMI >25 kg/m2 (36 women of mean age 28.6 +/- 6.0 years). In the control group there were 22 healthy women (mean age of 31.6 +/- 8.5 years). That group again was divided accordingly to BMI into two subgroups: the first with BMI <25 kg/m2 (ten women, mean age 30.2 +/- 8.4 years) and the second with BMI > 25 kg/m2 (12 women, mean age 31.7 +/- 8.7 years). The results demonstrated statistically significantly higher mean concentrations of sICAM-1 in women with PCOS as compared to healthy individuals from the whole control group and also from the control subgroup of women with BMI >25 kg/m2. There was no statistically significant difference in sICAM-1 concentration between the PCOS group and the control subgroup with BMI < or =25 kg/m2 In conclusion, higher concentrations of sICAM-1 in women with PCOS may confirm the presence of a higher risk for cardiovascular diseases in this group. Further studies are therefore necessary to identify both the factors that are responsible for the increase in sICAM-1 concentration and the clinical usefulness of routine sICAM-1 measurement in females with PCOS.

Circadian rhythm of androstendione and free testosterone in asthmatic women with postmenopausal hormone therapy.

OBJECTIVE: of this study was to assess daily rhythm of androstendione (delta4alpha) and free testosterone (FT) levels in postmenopausal asthmatic women before and after hormonal replacement therapy and the influence of inhaled glucocorticosteroids (GC). METHODS: 54 asthmatic and 20 healthy postmenopausal women (aged 48-59) before and after 6 months of estrogen plus progestin therapy (EPT) were studied. Hormone concentrations in serum (delta4alpha and FT) were assessed with the use of RIA method. Statistical analysis of the circadian rhythm was performed with the use of cosinor test according to Halberg et al RESULTS: Cosinor analysis of delta4alpha and FT secretion during the day showed existence of daily rhythm in three studied groups before as well as after postmenopausal hormone therapy (HT). A statistically significant decrease of circadian concentrations of delta4alpha and FT in groups of patients treated with GC was observed. Changes in amplitude of delta4alpha and FT rhythm between studied groups were not observed. However, displacement of rhythm acrophase of studied hormones in asthmatic women in comparison to control group before and after HT was shown. No significant differences in circadian values of delta4alpha and FT concentrations before HT use compared to values after HT were shown. CONCLUSIONS: Postmenopausal asthmatic women show diminished circadian concentrations of androstendione and free testosterone in serum caused among other things by inhalative GC. Postmenopausal hormone therapy did not influence any changes in function of studied endocrine organs.

Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters.

UNLABELLED: Several studies have demonstrated that low levels of serum adiponectin are present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim of our study was to determine whether serum adiponectin level is different between patients with polycystic ovarian syndrome (PCOS) and control subjects. We also investigated relationships between various cardiovascular risk factors, levels of serum adiponectin and other hormones, such as androstendione, testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin. We also analysed the correlation between serum adiponectin and free androgen index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control subjects, carefully matched by body mass index (BMI) and age, were enrolled in the study. The fasting blood samples were obtained and all participants underwent an oral 75 g glucose tolerance test. The prevalences of impaired glucose tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS group. PCOS women had increased androgen concentrations and higher free androgen index and decreased level of serum SHBG. Lower serum adiponectin concentrations were observed among cases than in controls (median 13.7 microg/ml vs 17.8 microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=-0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02). In contrast, the adiponectin level does not appear to be related to total testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found to be decreased in PCOS women with IGT compared to PCOS women with normal glucose tolerance, but after adjustment by BMI or WHR, the differences were no longer statistically significant. To exclude a possible confounding effect due to a higher prevalence of IGT in the PCOS group, this comparison was repeated for the subgroup of 58 PCOS women and 48 control women after excluding those with IGT. Neither adiponectin nor SHBG were significantly different between those subgroups. Multiple regression analysis revealed that serum adiponectin concentrations were best predicted by WHR, free androgen index and presence of IGT when all patients were considered. In PCOS subjects, the only independent predictor of adiponectin concentrations was glucose tolerance status. CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control women, and these differences were probably due to higher prevalence of IGT in these cases.

Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration.

PURPOSE: The aim of this study was to evaluate the ferric reducing ability of plasma (FRAP), selected enzymatic and non-enzymatic components of the antioxidative system, and the intensity of peroxidative processes in the blood of patients with age-related macular degeneration (AMD). METHODS: In the peripheral blood, we evaluated FRAP; concentrations of vitamins C, A, and E; and of thiols. We assayed the activity of enzymatic components of the antioxidative system-superoxide dismutase, catalase, ceruloplasmin and the concentration of reduced glutathione as an indicator of glutathione peroxidase activity. In order to determine the intensity of lipid peroxidation, we measured the concentrations of malondialdehyde and hydroxyalkenales (MDA-HNA) and conjugated diens (CD). RESULTS: We found a significant increase in FRAP in patients with AMD compared with the control group. The average concentrations of vitamins A and C were low and vitamins E and GSH were significantly higher in AMD than in the control group. The activity of almost all the antioxidative enzymes was high. We found a significant increase in MDA-HNA but no difference in CD. CONCLUSIONS: The significantly higher concentration of lipid peroxidation products in patients with AMD indicates an important pathogenic role of oxido-reduction disturbance. The high FRAP concentration may be one of the protective mechanisms in oxidation stress. The adaptive increase of the antioxidant barrier mostly involves the enzymatic components.

Adrenal cortex function in asthmatic patients following the discontinuation of chronic therapy with systemic glucocorticosteroids.

OBJECTIVE: To estimate the time it takes for adrenal cortex function in asthmatic patients to return to normal after discontinuation of chronic therapy with systemic glucocorticosteroids (GCs) and to assess the relationship between the duration of the disease, chronic therapy, and the return of the normal adrenal cortex functioning. MATERIALS AND METHODS: The study involved 58 asthmatic patients and 31 healthy volunteers (aged 20-69 years). Adrenal cortex function was evaluated with the Synacthen short test, and determining serum and urinary free cortisol levels after 1, 3, 6, 12, 18, and 21 months following the discontinuation of systemic therapy with GCs. RESULTS: A decreased adrenal reserve was observed 1 month after withdrawal of GCs in 50% of the chronically treated patients. Adrenal cortex function returned to normal in 55% of patients within 6 months, in 24% within 12 months, and in 14% within 15 months of discontinuation of systemic GCs administration. A significant positive correlation between the time taken for return to normal adrenal cortex function and duration of the disease and of GCs therapy was found. CONCLUSIONS: Symptoms of adrenal failure may develop in about 50% of asthmatic patients. In the majority of patients treated long term with systemic GCs, adrenal cortex function returns to normal within 6 months following discontinuation of GCs. The time of such return depends on the duration of the disease and of therapy with systemic GCs.

Influence of lighting conditions on daily rhythm of bone metabolism in rats and possible involvement of melatonin and other hormones in this process.

OBJECTIVE: To evaluate the influence of lighting conditions on daily fluctuations of biochemical markers of bone and mineral metabolism such as the activity of serum alkaline phosphatase (ALP), the concentration of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and inorganic phosphorus (iP) as well as urinary excretion of hydroxyproline (HYP) and calcium (Ca). In addition, possible involvement of daily secretion of melatonin (MEL), GH/IGF-I axis activity and parathyroid, thyroid, adrenocortical and gonadal function in this process. METHODS: Three series of 48 adult male Wistar rats weighing 180 +/- 10 g were conditioned to different lighting conditions for 4 weeks: 1. control group (LD 12:12 h, light on from 7.00 to 19.00); 2. short-day group (LD 0.5:23.5 h, light on from 7.00 to 7.30); 3. long-day group (LD 23.5:0.5 h, light on from 19.30 to 19.00). The blood was obtained by decapitation. Material for studies was collected every 3 hours during a day. The concentration of hormones, PICP and ICTP was determined with the use of RIA method, whereas ALP, iP, HYP and Ca levels were estimated spectrophotometrically. RESULTS: A significant influence of different lighting conditions on the daily profile of investigated markers of bone metabolism in rats was confirmed. Thus a short day was found to have an inducing effect upon the level of these markers, while a long day showed a suppressing effect. Furthermore, substantial changes in the values of amplitude and phase of their daily rhythms were found. Also some distinct anomalies in daily oscillations of ALP, PICP, ICTP, HYP and Ca were found which were dependent on the time of the day and showed a negative correlation with the changes in endogenous MEL concentrations. Moreover, ICTP, HYP and Ca concentrations correlated positively with daily fluctuations of IGF-I and triiodothyronine. CONCLUSIONS: Lighting conditions can influence daily fluctuations of studied bone metabolism markers in rats, and in the mechanism of this dependence the changes in endogenous MEL concentrations seem to play an important role. Secondary changes in daily IGF-I and triiodothyronine oscillations, caused by short- and long-day conditions, result in altered daily bone resorption rhythmicity.

The relationship between bone metabolism, melatonin and other hormones in sham-operated and pinealectomized rats.

OBJECTIVE: The influence of pinealectomy and long-term melatonin (MEL) administration on circadian oscillations of selected biochemical markers of bone metabolism [serum alkaline phosphatase (ALP) activity, carboxyterminal propeptide type I procollagen (PICP) and carboxyterminal telopeptide type I collagen (ICTP) concentrations as well as urinary excretion of hydroxyproline (HYP) and Ca] and possible involvement of circadian secretion of IGF-I, parathyroid, thyroid, adrenal cortex and gonads function in this mechanism was evaluated. METHODS: Studies were performed in 192 adult male Wistar rats weighing 145 +/- 9 g which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in a dose of 50 mg/100 g b.w. was administered intraperitonealy (daily between 17.00 and 18.00 h for a 4-week period). Material for studies (blood and urine) was collected every 3 hours during a day. Hormones, PICP and ICTP concentrations were determined with the use of RIA methods. whereas ALP, HYP and Ca values - spectrophotormetrically. RESULTS: The study has shown that pinealectomy had an inducing, while exogenous MEL a suppressing effect upon the level of investigated biochemical markers of bone metabolism. Furthermore, substantial changes in the values of amplitude and phase of their circadian oscillations were shown. Distinct, dependent on the time of day disturbances in circadian fluctuations of PICP, ICTP, HYP and Ca showing generally negative correlation with changes in endogenous MEL concentrations and positive with IGF-I and corticosterone (B) levels were found. In addition, changes in circadian oscillations of ALP and PICP correlated negatively with daily oscillations of calciotropic hormones and B. However, ICTP, HYP and Ca concentrations correlated positively with circadian fluctuations of B and FT3 (the latter only in sham operated rats receiving MEL). CONCLUSIONS: This study showed that both pinealectomy and long-term MEL administration influence the circadian rhythm of bone metabolism and that an important role in the mechanism of this dependence is played by the changes of endogenous MEL levels. Secondary changes in circadian oscillations of calciotropic hormones, IGF-I and corticosterone concentrations, caused by pinealectomy and long-term MEL administration result in altered bone metabolism rhythm.

Dynamic pattern of IGF-I and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis.

OBJECTIVE: To assess the relationship between the dynamic pattern of IGF-I levels and chosen biochemical markers of bone metabolism in ovariectomized rats - a model of postmenopausal osteoporosis. METHODS: Six-month-old rats were randomized to sham operation (control group) or ovariectomy. Serum levels of insulin-like growth factor (IGF-I) and chosen biochemical markers of bone metabolism (alkaline phosphatase - ALP, carboxyterminal propeptide of type I procollagen - PICP, cross-linked carboxyterminal telopeptide of type I collagen - ICTP in serum as well as urinary excretion of hydroxyproline - HYP and total calcium - Ca) were measured before (group 0) and 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 28 weeks after the operation. RESULTS: In a model of experimental osteoporosis induced by ovariectomy in female rats a distinct tendency to decrease the IGF-I concentrations was shown. Differences were significant in relation to the control group in a period from 2 to 28 weeks after operation. Ovariectomy stimulated the values of studied markers of bone metabolism; it was more intensified in regard to resorption markers. Significant ICTP and HYP concentrations' changes, in relation to the control group, were shown in the some period and total calcium - from 2 to 16 weeks after ovariectomy. However, the values of studied markers of bone formation were generally changing to a slight degree. Significant differences of ALP activity, in relation to the control group, were observed only at 8 and 20 weeks, while those of PICP concentrations were found at in 4, 8 and 12 weeks after the operation. The alterations in the levels of IGF-I correlated significantly and negatively with the changes in ALP activity as well as in PICP, ICTP, HYP and Ca concentrations both in ovariectomized and control rats. This relation was more expressed in the ovariectomized group. CONCLUSIONS: Our findings suggest that secondary changes in IGF-I concentration, due to the deficiency of sex hormones, results in altered bone metabolism in ovariectomized rats.