Cerebrospinal fluid plasminogen activator inhibitor-1 in patients with neurological disease.

AIM: To study cerebrospinal fluid (CSF) concentrations of plasminogen activator inhibitor type-1 (PAI-1) in patients with neurological disease. METHODS: CSF PAI-1 concentrations were measured in 51 patients with neurological disease and 20 reference subjects using an ELISA. The patient group comprised three patients with viral meningitis, 20 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia (with central nervous system involvement), and 19 with multiple sclerosis. RESULTS: Raised PAI-1 concentrations were observed in patients with leukaemia, encephalitis and multiple sclerosis. There was no difference in the mean concentrations of PAI-1 in patients with meningitis when compared with the reference subjects. The highest mean (SEM) PAI-1 concentration was found in patients with leukaemia (1.28 (0.36) ng/ml), and the next highest in those with encephalitis (1.19 (0.20) ng/ml). these values were much higher than those in patients with viral meningitis. In a previous report, raised CSF tissue-type plasminogen activator (tPA) activities were detected in patients with multiple sclerosis, leukaemia and encephalitis, with mean activities in decreasing order. PAI-1 concentrations in the same patients were the reverse of their corresponding tPA activities, being higher in those with leukaemia and encephalitis, than in patients with multiple sclerosis. There was no association between CSF PAI-1 concentrations and age in either patients or controls. Similarly, there was no association between CSF PAI-1 concentrations and urokinase-type plasminogen activator (uPA). CONCLUSIONS: Raised CSF PAI-1 concentrations may be used as a non-specific marker of neurological disease. Moreover, PAI-1 may play an important role in regulating the functions tPA, and probably uPA, in CSF.

Cerebrospinal fluid activity of tissue plasminogen activator in patients with neurological diseases.

AIM: To study cerebrospinal fluid (CSF) activity of tissue plasminogen activator (tPA) in patients with neurological diseases. METHODS: CSF tPA and urokinase (uPA) activities were studied using an immunocapture assay and zymography in 44 patients with neurological disease and 20 reference subjects. The patient group comprised three patients with meningitis, 21 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia, seven with multiple sclerosis, three with facial paresis, and one with polyradiculitis. RESULTS: Raised tPA activities were observed in patients with multiple sclerosis, leukaemia and encephalitis. In contrast, there were no differences in the mean activities of tPA in patients with meningitis or other diseases compared with the reference subjects. The highest tPA activities were found in patients with multiple sclerosis. The mean activity in patients with leukaemia was higher than in those with meningitis and polyradiculitis, but not encephalitis and facial paresis. Although the CSF tPA activity correlated positively with age in reference subjects, no correlation was observed in patients. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples were quantitated. Some of the samples had quantifiable levels of uPA activity: three of seven multiple sclerosis samples, 10 of 21 samples from patients with encephalitis and five of nine leukaemic samples. The highest activities were recorded in patients with leukaemia. uPA was not detected in the CSF of the patients with meningitis, facial paresis or polyradiculitis. CONCLUSIONS: Plasminogen activator activity can be measured reliably in CSF and the assessment of tPA activity may be useful for studying the pathogenesis of neurological diseases.

Tissue plasminogen activator gene expression in multiple sclerosis brain tissue.

Recent studies have implicated tissue-type plasminogen activator (tPA) in neurodegeneration. We studied multiple sclerosis (MS) brain tissue for tPA gene and protein expression in comparison with reference tissue, by in situ hybridisation and immunohistochemistry. MS is characterised by demyelination in the central nervous system. In this study, neuronal cell bodies in MS brain showed high expression of tPA mRNA and protein, while in reference brains, staining for protein and mRNA expression were very low in neurons and mostly restricted to blood vessel walls. In MS, there was an additional staining of mononuclear cells within perivascular cuffs and foamy macrophages within demyelinating plaques. In view of evidence that the final process of demyelination in MS is thought to be enzyme-mediated, our work suggests the involvement of tPA and by inference plasmin, in the demyelinating process. Blocking tPA or plasmin activity may be a potentially beneficial therapeutic approach in MS.

Seroprevalence and coprevalence of HIV and HBsAg in Nigerian children with/without protein energy malnutrition.

In order to assess the seroprevalence and coprevalence of hepatitis-B surface antigen (HBsAg), human immunodeficiency virus-1 and -2 (HIV-1 and -2) antibodies in Nigerian children with/without protein energy malnutrition (PEM), we studied plasma specimens of 206 children with PEM and 200 apparently healthy reference children aged between 1 and 3 years by enzyme-linked immunosorbent assays (ELISA). HIV-seropositive cases were confirmed by immunoblotting (IB). Of the children studied, eight (4%) of the healthy and four (1.9%) of the malnourished (P = 0.22, Fisher's exact test) were positive for HIV-1 antibodies, 40 (20%) of the healthy and 54 (26%) of the malnourished (P = 0.14) were positive for HBsAg, and five (2.5%) of the healthy and four (1.9%) of the malnourished (P = 0.70) were positive for both HIV-1/HBsAg. No case of HIV-2 antibodies was found. While the seroprevalence of HBsAg was higher in the malnourished subjects, the reverse was the case with HIV antibodies. However, all the four HIV-1-positive malnourished children and five of eight of the HIV-1-positive reference children were simultaneously positive for HBsAg. This is the first epidemiological report on the seroprevalence and coprevalence of HIV and HBsAg in apparently healthy and malnourished Nigerian children.

Serum zinc, copper and magnesium in sickle cell disease at Ibadan, south western Nigeria.

Serum zinc, copper and magnesium were studied in patients with sickle cell disease in the steady state. There was significantly lower serum zinc concentration (P < 0.01) and significantly higher serum copper and magnesium in haemoglobin S patients compared with controls (HbA). In haemoglobin SC patients, there was a significant reduction in serum zinc (P < 0.01) but no significant difference in serum copper and magnesium concentrations compared with the controls. There was no significant difference in serum zinc concentration between the HbS and HbS + C patients. However there were significantly higher serum copper and magnesium in HbS than HbS + C patients (P < 0.01) The level of serum zinc has no correlation with the steady state Haematocrit or severity index score in HbS and HbS + C patients.

Assessment of plasma fibronectin in malnourished Nigerian children.

BACKGROUND: Severe malnutrition is associated with septic infections. The concentrations of fibronectin, albumin, and transferrin in plasma were measured in three groups of children with protein-energy malnutrition, aged 1-3 years, each group comprising 20 children. The aim of which was to test whether plasma fibronectin, being an opsonic protein, was reduced in such children, and if it was a useful index for assessing the severity of malnutrition. METHODS: The concentrations of fibronectin, albumin, and transferrin in plasma were studied by enzyme immunoassay/ immunoblotting, spectrophotometry and immunoturbidimetry respectively. RESULTS: All values were significantly lower in the patients with malnutrition than in the age- and sex-matched well-nourished Nigerian reference children. Within the malnourished group, the fibronectin value was evenly reduced in all subgroups. Albumin and transferrin values were lowest in the patients with kwashiorkor, highest in the marasmic patients, and intermediate in the patients with marasmic kwashiorkor; the values correlated mutually in individual cases as well, but not with the fibronectin levels. Neither plasma fibronectin fragmentation nor tissue fibronectin was detected in any patient with malnutrition or in the reference subjects. CONCLUSIONS: The reduced plasma fibronectin values in these patients may be due to reduced synthesis by the liver, as evidenced by the equally reduced albumin and transferrin concentrations and/or to the multiple infections characteristic of the patients.