Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats.

BACKGROUND/AIM: There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P - 9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). RESULTS: Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 +/- 0.2 vs 1.12 +/- 0.04 mmol/L; p < 0.001); higher mean serum phosphorus (2.42 +/- 0.46 vs 2.05 +/- 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 +/- 0.46 vs 3.05 +/- 0.58; p < 0.01) and significantly increased P1NP (489.22 +/- 46.77 vs 361.9 +/- 53.01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the contol group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 +/- 0.03 vs 1.15 +/- 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 +/- 0.13 vs 1.89 +/- 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. CONCLUSIONS: Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory.

Schizophrenia is associated with increased levels of serum Fas and FasL.

BACKGROUND: A growing body of evidence suggests that the apoptotic process is dysregulated in schizophrenia. However, only a few studies have evaluated apoptotic markers in vivo in patients or their cell cultures. METHODS: Serum concentrations of Fas receptor (Fas/APO-1) and Fas ligand (FasL) were measured by ELISA techniques. The differences were tested according to the patients' demographic, clinical and drug treatment characteristics. The clinical accuracy of the examined markers was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: In this case-controlled study both sFas/APO-1 and FasL were significantly higher in the patients with schizophrenia than in the controls. An increase in apoptotic markers was independent of the symptomatology, drug treatment, heredity, the first onset of the disease, the duration of the psychotic disease as well as the tobacco abuse. A significant negative correlation between the duration of the disease and sFasL concentration was found. At the same time, a significant positive correlation was found between sFasL and lymphocyte caspase-3 activity. ROC curve analysis showed that sFasL was the most strongly associated with the presence of schizophrenia. CONCLUSIONS: We can conclude that the extrinsic apoptotic pathway is dysregulated in schizophrenia and sFasL may be a clinically useful disease predictor.

Serum Fas/FasL levels in dependence on clinical presentations of coronary disease and their relationship with risk factors.

BACKGROUND/AIM: Ischemic heart disease is mostly a consequence of atherosclerosis. Besides the inflammation, the Fas/Fas ligand (FasL)/caspase death pathway is documented to be activated in atherosclerotic lesions. The aim of this study was to compare the values of soluble forms of Fas and FasL in patients with different presentations of coronary disease and to correlate Fas/FasL with risk factors. METHODS: We studied 30 patients with chronic stable angina pectoris (SAP), 27 with non-stable angina pectoris (NSAP), and 39 with acute ST-elevation myocardial infarction (STEMI) and 27 age-matched healthy volunteers (the control group). Serum Fas/APO1 and FasL concentrations were determined using a commercially available enzyme-linked immunoassays (ELISA). RESULTS: Fas/APO-1 levels in the STEMI patients (6.981 +/- 2.689 ng/mL) were significantly higher than Fas levels in the controls (5.092 +/- 1.252 ng/mL, p < 0.01), but not significantly higher than Fas values in the SAP (5.952 +/- 2.069 ng/mL) and the USAP patients (5.627 +/- 2.270 ng/ml). Levels of FasL did not show any significant difference among the studied groups. In the SAP patients Fas/APO1 showed a significant positive correlation with high sensitivity C-reactive protein (hsCRP) (p < 0.05) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (p < 0.05), while FasL showed a significant positive correlation with low-density lipoprotein cholesterol (LDL-C) (p < 0.05). Fas levels between the patients having cholesterol within normal range and those whose cholesterol was above the normal range showed a significant difference (p < 0.05) only in the NSAP patients. Fas and FasL levels between the patients with hsCRP lower than 3.0 mg/L and those with hsCRP higher than 3.0 mg/L of the SAP group showed a significant differences (p < 0.001, p < 0.05, respectively). Strong correlation between Fas concentration and diabetes mellitus (p < 0.05) and FasL concentrations and both cholesterol (p < 0.01) and triglycerides (p < 0.01) in the NSAP patients was observed. The patients in the SAP group showed no strong correlation between Fas and FasL concentration and risk factors. CONCLUSIONS: The obtained results showed that apoptotic process is dysregulated in the patients with ischemic heart disease. Interdependence between Fas and FasL and inflammatory and lipid markers as well as with cardiovascular risk factors was established.

Plasma nitrite/nitrate concentrations in patients with schizophrenia.

BACKGROUND: Nitric oxide (NO) is known to be a signaling molecule with many physiogical functions including apoptotic process regulation. Since apoptosis may contribute to the pathophysiology of schizophrenia, this study was undertaken to determine the plasma concentrations of NO in schizophrenics. METHODS: Nitrite/nitrate (NO(2)(-)/NO(3)(-)) concentrations were measured in plasma from 40 patients with schizophrenia, and 36 age- and gender-matched healthy persons using a colorimetric test. RESULTS: Plasma NO(2)(-)/NO(3)(-) concentrations were significantly higher in patients with schizophrenia (102.8+/-34.7 micromol/L, p<0.0001) than in controls (69.2+/-13.2 micromol/L). Also, mean NO(2)(-)/NO(3)(-) values in female patients and controls were significantly higher (118.2+/-44.7 micromol/L, p<0.001; 74.8+/-16.1 micromol/L, p<0.05, respectively) compared to males (94.7+/-25.3 micromol/L, 67.6+/-10.8 micromol/L). Significant correlation was seen between plasma NO(2)(-)/NO(3)(-) concentrations and heredity, number of episodes and peripheral blood mononuclear cell (PBMC) caspase-3 activity, which was significantly higher in patients than in controls (p<0.05). There was no significant difference in NO(2)(-)/NO(3)(-) concentrations between patients with different Positive and Negative Syndrome Scale (PANSS) scores or between patients treated with haloperidol (97.2+/-31.2 micromol/L) and those treated with other atypical antipsychotic drugs (109.8+/-33.7 micromol/L). Both parameters showed no significant differences between smokers and non-smokers. CONCLUSIONS: This study showed that plasma NO(2)(-)/NO(3)(-) concentrations were significantly increased in patients with schizophrenia, being significantly higher in female than male patients, and showing a significant correlation with heredity, number of episodes and PBMC caspase-3 activity. These results suggest that NO could be considered an inducer or regulator of apoptosis in patients with schizophrenia.

Glycosylation of IgG B cell receptor (IgG BCR) in multiple myeloma: relationship between sialylation and the signal activity of IgG BCR.

Little is known about the glycosylation of the isotype switched B cell receptor (BCR) in multiple myeloma, and the way it might affect receptor function. In this work IgG BCRs isolated from the individual lysates of peripheral blood lymphocytes (PBL) of 32 patients with IgG multiple myeloma and healthy controls were investigated for the expression of sialic acid (SA), galactose (Gal) and N-acetylglucosamine (GlcNAc), the sugars known to specify the glycoforms of human serum IgG. The degree of glycosylation and signaling status of all 32 isolated myeloma IgG BCRs were correlated and compared with the glycosylation of the IgG paraproteins isolated from sera of the same patients. It was shown that BCR IgG in myeloma is more heavily sialylated when compared with normal controls, that the increased sialylation of IgG BCR is associated with higher levels of tyrosine phosphorylation (signaling activity) of the IgG BCR supramolecular complex and that BCR IgG and serum IgG paraprotein from the same patient differed in all cases in the levels of terminal sugar expression. The results suggest that the development of the malignant clone in MM from post-switch B cells expressing IgG BCR at their surfaces to plasma cells secreting IgG paraprotein may be followed by permanent glycosylation changes in the IgG molecules.