Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Neuropsychiatric systemic lupus erythematosus refers to central and peripheral nervous system involvement, which may occur secondary to antineuronal antibodies crossing the blood-brain barrier that preferentially target cells in the hippocampus leading to abnormal hypermetabolism and atrophy. Thus, we hypothesized that alterations in BBB permeability, detected on dynamic contrast-enhanced MR imaging, occur in the hippocampus in patients with systemic lupus erythematosus before development of neuropsychiatric systemic lupus erythematosus. MATERIALS AND METHODS: Six patients with systemic lupus erythematosus without neuropsychiatric systemic lupus erythematosus and 5 healthy controls underwent dynamic contrast-enhanced MR imaging with postprocessing into BBB permeability parameters (K trans and Ve) and CBF. Standardized methods selected ROI sampling of the abnormal brain regions detected on FDG-PET. The mean and SD of K trans, Ve, and CBF were calculated. Linear regression and nonparametric Spearman rank correlation analyses of K trans and Ve with CBF were performed. Dynamic contrast-enhanced curves and the area under the curve were generated for each brain region. Student t test comparisons were performed. RESULTS: Quantitative data revealed that patients with systemic lupus erythematosus have statistically increased K trans (P < .001) and Ve (P < .001) compared with controls. In patients with systemic lupus erythematosus, statistically significant positive correlations were seen between K trans (P < .001) and Ve (P < .001) with CBF. Furthermore, the mean area under the curve revealed statistically increased BBB permeability in the hippocampus (P = .02) compared with other brain regions in patients with systemic lupus erythematosus compared with controls. CONCLUSIONS: These initial findings are proof-of-concept to support the hypothesis that patients with systemic lupus erythematosus have increased BBB permeability, specifically in the hippocampus, compared with other brain regions. These findings may advance our understanding of the underlying pathophysiology affecting the brain in autoimmune diseases.

Dynamic Contrast-Enhanced MRI Reveals Unique Blood-Brain Barrier Permeability Characteristics in the Hippocampus in the Normal Brain.

We report a prospective dynamic contrast-enhanced MR imaging analysis of region-specific blood-brain barrier permeability in 5 healthy subjects. By means of standardized postprocessing and ROI sampling methods, the hippocampi revealed significantly elevated area under the dynamic contrast-enhanced curve and significantly increased blood-brain barrier permeability metrics (volume transfer constant and volume in the extravascular extracellular space) from model-based quantitation. These findings suggest unique blood-brain barrier permeability characteristics in the hippocampus, which are concordant with previous animal studies, potentially laying the groundwork for future studies assessing patient populations in which hippocampal pathology plays a role.

[Hyperinsulinemia in obesity and diseases of internal medicine].

We analysed fasting serum insulin levels and its correlation with common internal medical diseases in 91 cases with obesity (BMI > 24) and that in 76 nonobese cases. The mean fasting serum insulin level in obese group was higher significantly than that in nonobese group (P < 0.001). The incidences of hypertension, coronary heart disease, cerebrovascular disease, non-insulin-dependent diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia and serum low level of HDL-C in obese group were also higher significantly than that in nonobese group (P < 0.05 and < 0.01 respectively). The main cause of many medical diseases coexisted with obesity is hyperinsulinemia. We think that the first choice of therapy to this kind of diseases should be to reduce the body weight and to decrease the insulin resistance.

[The effect of lovastatin in the treatment of primary hypercholesterolemia].

The effect of Lovastatin, an HMG. CoA reductase inhibitor, on serum lipids and apolipoproteins was studied in 40 cases of primary hypercholesterolemia in a 4-month period of treatment. The level of serum lipids did not change significantly after a 35-day period of placebo treatment as compared with that of the baseline (P greater than 0.5). The patients then took Lovastatin with the evening meal in a daily dose from 20 to 80 mg for 3 months. The results were as follows: Lovastatin reduced significantly the mean serum level of total cholesterol (TC) by 31.5% (P less than 0.001), LDL-C by 39.8% (P less than 0.001), Apo-B by 27.3% (P less than 0.002), and the ratio TC/HDL-C by 35.9% (P less than 0.01). It also reduced the mean serum level of triglycerides (TG) by 22.1% (P greater than 0.05) and increased that of HDL-C by 6.3% (P greater than 0.2) and Apo-AI by 1.6% (P greater than 0.5), but without much significance. The drug was well tolerated by all the patients. Transient elevation of CPK was noticed in 2 patients and AKP in one patient. 7 patients complained of gastrointestinal discomfort. All these side effects did not necessitate stop of the medication. We are, therefore, of the opinion that Lovastatin is an effective agent for lowering the serum level of TC, LDL-C and Apo-B.

[Detection and analysis of HBV antigen protein in kidney tissue and HBV DNA in serum and kidney tissue of patients with HBsAg+ IgA nephropathy.].

BACKGROUND: To explore the relationship between hepatitis B virus (HBV) infection and development of IgA nephropathy. METHODS: HBsAg and HBcAg protein in renal biopsy specimens of 32 cases was detected on frozen sections and HBV DNA was detected in paraffin section of renal biopsies and in serum of 42 HBsAg positive cases. RESULTS: The positive rate of HBAg in renal biopsies of IgA nephropathy was 59.1%, and 63.6% in non-IgA nephropathy, there was no significant difference between them. In 42 cases biopsies of renal tissues, only five were HBV-DNA positive (11.9%). The five cases were HBsAg, HBcAb and HBeAg positive, the pathological diagnosis of two cases were mesangial proliferative glomerulonephritis; one had minimal change of glomerulonephritis; and one had basement membrane change; and only one had IgA nephropathy. At the same time, in 42 HBsAg+ cases the serum specimens were detected; 12 cases were positive for HBsAg, HBcAg and HBeAg, in whom serum HBV-DNA was positive, but only 5 were positive for HBV-DNA in renal biopsy tissue, and HBV-DNA was negative in other 30 blood serum and tissue specimens. CONCLUSION: The difference in expression of HBsAg, HBcAb and HBeAg protein between IgA nephropathy and non-IgA nephropathy tissue from renal biopsy was not significant. There is no direct relationship between HBV infection and IgA nephropathy.