Band 11, Heft 2

In this study, we assessed a possible correlation of CD4 counts with the low-cost progression markers neopterin, 132-microglobulin (B2M), total lymphocyte count (TLC) and hemoglobin, and we investigated associations between progression :narkers and clinical parameters in HIV -1 seropositive Zambians. Of 147 HIV- 1 seropositive patients presenting to an outpatient clinic in Lusaka, blood was taken for CD4 counts, serum progression markers and full blood count. A detailed clinical history and medical examination was taken at that point, and the patients were seen 3··monthly over the following 12 months. Further CD4 counts were taken after 6 and 12 months. Neopterin, B2M: lymphocyte count, and hemoglobin showed a strong correlation with CD4 count. Of the serum progression markers, neopterin was more sensitive than B2M to detect HIV related symptoms and to predict weight loss and death in the follow-up period. Lymphocyte count and hemoglobin were significantly lower in patients with oral candidiasis and those falling sick or dying in the follow-up period. Hemoglobin was also associated with past diarrhoea. When stratified by sex, the associations of hemoglobin were very strong in males, but weaker in females . In conclusion, neopterin and B2M correlate well with CD 4 counts in this African population. Neopterin appears to be more sensitive for the clinical evaluation o: the patients in this study. Hemoglobin might only be useful as a progression marker in male individuals .

Alcoholic cirrhosis and viral cirrhosis are associated with alterations of immune system function and cytokine production. Our aim was to investigate whether serum concentrations of soluble receptors for interleukin-2 (sIL- 2 R) and tumor necrosis factor (55kD-type, sTNFR-55), and serum neopterin can be used as markers to establish differences in etiology and severity in liver cirrhosis and to determine whether they correlate with laboratory and clinical parameters. Thirty three patients with alcoholic and 15 with viral cirrhosis (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy controls were studied. Serum concentrations of sIL2-R, sTNFR-55 and neopterin were significantly raised in patients. No significant differences between alcoholic and viral cirrhosis were found. The concentrations of sIL-2 Rand sTNFR-55 were significantly higher in patients with more severe disease. There existed correlations b<!tween sIL-2R and sTNFR-55 (rs = 0.50, P < 0.001) and between both soluble receptors and the Child-Pugh score (sTNF-R55: rs = 0.70, p < 0.001; sIL-2R: rs = 0.33, p < 0.05) and serum albumin. The results are likely to reflect that the monocyte-macrophage and T-cell functions are stimulated in patients with liver cirrhosis independently of the etiology of the disease, and the persistent activation of the immune system occurs in cirrhosis even at the end stage of the disease. Chronic immune activation might have deletereous consequences on the evolution of cirrhosis.

In fifty-four patients with Alzheimer's disease [AD (14 males, 40 females, age 77.1 2: 7.4 years)], free of any infection and twenty-two age-matched healthy controls with normal mental status (9 males, 13 females, age 74.9 ± 9.0 years) serum concentrations of soluble parameters of immune activation including neopterin, 55 kDa-type soluble tumor necrosis factor receptor (sTNF-RSS), soluble interleukin-2 receptor (sIL-2R), immunoglobulins A, M and G, complement components C3 and C4, circulating immune complexes, and soluble CD23 as well as a panel of routine laboratory tests were determined. Compared to controls, significantly higher concentrations of sIL-2R (p < 0.01), neopterin (p < 0.01), sTNF-R55. sCD23 and IgA (all p < O.OS) were found in AD patients. Patients with greater cognitive impairment had higher concentrations of neopterin and sTNF-R55. An inverse correlation was seen between mini mental state (MMS) and sTNF-R55 (r = -0.43S; P < 0.01) and neopterin (rs = -0.289; P < 0.05). Our data show increased serum concentrations of immune activation markers in patients with AD correlating with the severity of dementia. Increased neopterin concentrations together with increased slNF-R55 and sIL-2R imply a chronic state of peripheral immune activation in the course of AD. Our data underscore previous reports on the effect of anti-inflammatory drugs in therapy and prevention of AD.

Serum concentrations of soluble intercellular adhesion molecules, sICAM-I , sICAM-3 and sP-selectin, of serum soluble cytokine receptors, sIL-2R, and sTNF-R55 and of neopterin were measured by commercially available immunoassays in 35 patients with rheumatoid arthritis (RA). Serum sICAM-I, sICAM-3 and sPselectin were significantly elevated in patients with RA compared with healthy controls. Concentrations of sPselectin and sICAM-3 correlated with disease activity and severity indices. sICAM-3 levels significantly correlated with sTNF-R55 and neopterin. There were significant correlations between neopterin and sIL-2R and between sTNF-R55 and sIL-2R. The measurement of sP-selectin and sICAM-3 levels in patients with RA might become useful for monitoring disease activity.

We describe the impact of dihydroneopterin on the formation of superoxide radicals. As radical source ferrous iron in air-saturated aequeous solution was used. Detection of superoxide was achieved using reduction of nitroblue tetrazolium to formazan. Dihydroneopterin decreases formazan formation when high concentrations of ferrous iron are used which induce a rapid superoxide formation within minutes. On the other hand, when low concentrations of ferrous iron are used, addition of dihydroneopterin to the assay mixture leads to an increase ir. formazan formation for several hours of incubation. We therefore conclude that the radical promoting activity of dihydroneopterin is physiologically more relevant compared to its radical scavenging properties.

Folate metabolism has been studied in 7 Gy whole body y-irradiated mice. Considerable changes in the formyl and methyl tetrahydrofolate derivatives were observed in the liver at various stages after irradiation. Methyltetrahydrofolate polyglutamate cofactors were reduced to a considerable extent in the irradiated group. Significant levels of oxidized folates such as pteroyl mono-, di-, and tetra- glutamyl forms were found only in the irradiated liver indicative of oxidative changes. Methylenetetrahydrofolate reductase, the enzyme synthesizing methyltetrahydrofolates was impaired 35-40% in irradiated animals possibly leading to an impairment in methyltetrahydrofolate synthesis. Folylpolyglutamate hydrolase which hydrolyzes polyglutamylfolates to simpler forms, showed an immediate spurt in the activity but returned to normal values, 48-72 h after irradiation. An increased lysosomal membrane damage as assessed by higher free-amino acid pool was observed in irradiated mice.