Brain-derived neurotrophic factor and its serum levels in schizophrenic patients.

INTRODUCTION: Neurotrophins have an important role in regulating the development and maintenance of the peripheral and central nervous systems' function. Thus, the neurotrophin hypothesis of schizophrenia has postulated that the changes in the brain of schizophrenic patients are the result of disturbances of developing processes involving these molecules. AIM: We analyse in the present study the changes in the serum levels of brain-derived neurotrophic factor (BDNF) in schizophrenic patients as possible epiphenomena of underlying alterations of the neurotrophic factor in central nervous system, reflecting its role in the pathophysiology of schizophrenia. PATIENTS AND METHODS: Twenty-one schizophrenic patients satisfying the DSM-IV criteria for diagnosis of schizophrenia were enrolled in the study. The control group consisted of 28 age-matched mentally healthy subjects. Serum BDNF levels were determined in patients and normal controls using ELISA (Chemicon International, USA & Canada). The data were analyzed statistically with Student's t- test in SPSS 9.0. RESULTS: The serum BDNF levels were lower in the schizophrenic patients than in the control subjects, reaching statistically significant difference (t = 2.72, p = 0.009). Female patients had lower serum BDNF levels than the male patients but the difference fell short of statistical significance (t = 0.1, p = 0.9). CONCLUSIONS: The BDNF reduction in serum indicates a potential deficit in neurotrophic factor release in patients with schizophrenia and support the concept that BDNF might be associated with schizophrenia.

Effect of moderate and high dose simvastatin on adhesion molecules in severe hypercholesterolemia after targeting the LDL-cholesterol--a randomised, placebo-controlled study.

INTRODUCTION: The effect of statins on the levels of cell adhesion molecules (CAM) is discussed in the literature as one of the pleiotropic effects of the drugs. This effect is one of the ways that could be used to control the initial stage of atherogenesis. The research in this field is inadequate and controversial. Prevention guidelines recommend that target levels of LDL cholesterol in high-risk patients should be less than 2.6 mmol/l. If the primary target is LDL-cholesterol, it is doubtful if patients can have any significant changes in the levels of the cell adhesion molecules (CAM). AIM: Study the effect of simvastatin administered in a moderate dose of 40 mg and in a high dose of 80 mg on endothelium activation in the context of the plasma levels of soluble cellular adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin) in recently diagnosed untreated severe hypercholesterolemia after reaching target levels for the LDL-cholesterol below 2.6 mmol/1. PATIENTS AND METHODS: One hundred patients (aged > 16 years) were included in the study. Hypercholesterolemia was defined as fasting total serum cholesterol level greater than 7.5 mmol/l and LDL-cholesterol > 4.9 mmol/l. The study was carried out in three phases, the main goal being titration of simvastatin dose from 40 to 80 mg with the purpose of achieving the target LDL level of < 2.6 mmol/l in a randomised placebo-controlled study. RESULTS: There was a statistically significant reduction of sVCAM-1 following the 80-mg simvastatin therapy for one month after reaching target levels of LDL-cholesterol < 2.6 mmol/l in hypercholesterolemic patients in comparison with the moderate dose (40 mg) of simvastatin for one month (p < 0.001). The results of the study demonstrated that simvastatin in a dose of 80 mg exerted an effect on the levels of some CAM, and particularly on VCAM-1 in contrast to the same drug used in a dose of 40 mg. CONCLUSION: As different statins most likely have a distinctly specific effect on different adhesion molecules, this study seeks to establish a suitable panel of such adhesion molecules that may be used in monitoring statin therapy.

Effect of moderate and high-dose simvastatin on asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.

The assumption that statin therapy can decrease asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logical and yet arises some controversy. The aim of the present study is to compare the effects of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine and total homocysteine levels in patients with newly detected severe hypercholesterolemia (after target LDL-C levels, ≤2.6 mmol/L, are reached). The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol ≥7.5 mmol/L and low-density lipoprotein cholesterol ≥4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocysteine-by a high-performance liquid chromatographic method. There was a statistically significant decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein-B levels as well as in the apolipoprotein-B/apolipoprotein-A1 index after a 1-month therapy with 40 mg simvastatin (P <0.001). Asymmetric dimethylarginine and total homocysteine levels were also decreased but the difference did not reach statistical significance (P= 0.571; P= 0.569). A dose-dependent effect was established, comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, and apolipoprotein-B). Asymmetric dimethylarginine and total homocysteine levels were lowered significantly with 80 mg simvastatin (P <0.001; P= 0.038). In conclusion, optimizing the target values of low-density lipoprotein cholesterol, a moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to a high dose (80 mg) after target LDL-C levels are reached (≤2.6 mmol/L) in patients with newly detected severe hypercholesterolemia.

Simvastatin and asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.

BACKGROUND: The idea that statin therapy decreases asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logic. However, controversy exists in the literature concerning this issue. This study compares the effect of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine levels in patients with newly detected severe hypercholesterolemia (after targeted LDL levels of < or = 2.6 mmol/L are reached). METHODS: The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol > or = 7.5 mmol/L and low-density lipoprotein cholesterol > or = 4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocystein by the high performance liquid chromatography method. RESULTS: A statistically significant decrease exists in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apolipoprotein-B levels as well as apolipoprotein-B/apolipoprotein-A1 index following one month of 40 mg simvastatin therapy (P < 0.001). Asymmetric dimethylarginine and total homocystein levels were also decreased but the difference was not significant (p = 0.571; p = 0.569). A dose-dependent effect was established comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, apolipoprotein-B). Asymmetric dimethylarginine and total homocystein levels showed a statistically significant decrease with 80 mg simvastatin (p < 0.001; p = 0.038). In the group of 40 patients, who had reached LDL-cholesterol target levels on 80 mg simvastatin, a reduction in ADMA levels demonstrated a statistically significant correlation with the reduction of LDL-cholesterol (r(xy) = 0.355; p < 0.01) and of Apo-B (r(xy) = 0.508; p < 0.001). The backward selection process selected percent ApoB-change as the most important statistically significant factor related to percent ADMA-change (F = 21.127; p = 0.001; R2 = 0.265). CONCLUSIONS: Optimizing the target values of low-density lipoprotein cholesterol to the moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to high dose (80 mg) after targeted LDL of < or = 2.6 mmol/L levels are reached in patients with newly detected severe hypercholesterolemia.

Role of some biomarkers of atherogenic risk in the screening for molecular defects in the low density lipoprotein receptor in severe hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is difficult to diagnose because of different expressions of the defective gene in low density lipoprotein (LDL) receptor mutation carriers and the presence of elevated LDL levels in noncarriers. AIM: To study specific biomarkers of atherogenic risk in carriers and noncarriers of low density lipoprotein receptor (LDLR) defective gene and utilize them to screen in molecular biological analysis for defects in the LDL receptor (spot mutation and polymorphism) in severe hypercholesterolemia. PATIENTS AND METHODS: We investigated 120 patients after screening using the Simon-Broome criteria. According to whether there were molecular defects or not, the patients were assigned to two groups--carriers (22 patients, 18.33%) and non-carriers (98 patients, 81.67%). Total cholesterol, triglycerides, HDL cholesterol, apolipoproteins Apo-B and Al were determined using routine methods. LDL-cholesterol was determined by direct methods. ELISA was used in determining the soluble cell adhesion molecules (sICAM-1, sVCAM-1), P-selectine and E-selectine, and high-performance liquid chromatography--total homocysteine. RESULTS: There were no significant differences in gender and anthropometric parameters (P > 0.05) between carriers and non-carriers, but the groups differed significantly in age (P < 0.001). No significant differences were found between the groups in the routine lip profile, the atherogenic lipid index, apolipoproteins B and A1, ADMA, total homocysteine, and the soluble cell adhesion molecules (P > 0.05). We found a statistically significant difference only for the Apo-B/Apo-A1 index in values non standardized by age, which was confirmed after standardization. CONCLUSIONS: Examining all 18 exons of LDLR gene in patients with severe HC we found that 18.33% of them were carriers of mutations and polymorphisms. There was no correlation between the presence of a molecular defect and the routine lipid profile, ADMA, total homocysteine and the soluble cell adhesion molecules; the presence of a molecular defect however, correlated with the Apo-B/Apo-A1 index.

Computertomographic findings of structural brain anomalies in schizophrenic patients in support of the neurodevelopmental hypothesis of the disorder.

AIM: The aim of the study was to make a comparative CT examination of schizophrenic patients and find lifetime criteria for recognition of brain changes in schizophrenia. MATERIAL AND METHODS: Twenty-two schizophrenic inpatients (mean age 32.86 +/- 2.65 yrs) satisfying the DSM-IV criteria for schizophrenia were examined. The control group comprised 27 clinically healthy subjects (16 men, 11 women, mean age 46.44 +/- 2.32 yrs) all of Bulgarian ancestry. All subjects underwent CT examination without venous enhancement at an examination angle of + 15 degrees-20 degrees in relation to the orbitomeatal line. Cortical atrophy was assessed according to criteria determining the external and internal liquor spaces (after Meese and Groome). RESULTS: There is a consistent low-grade enlargement of the brain ventricles. The variables have increased values (decreased for CMI) in the schizophrenic patients compared with the controls. The patients show moderately increased width of the lateral sulcus and brain convexity sulci. CONCLUSION: The brain tissue loss and enlarged extracerebral space suggest that the observed evidence of cortical loss in schizophrenic patients reflects a pathological process operating before completion of the brain growth.