Remarkably elevated levels of phospholipase A2 (PLA2)
are measurable in human blood samples in cases of
acute pancreatitis. The source of the enzyme was first
thought to be exclusively the pancreas, but now it is
generally accepted that two isoenzymes – the pancreatic
PLA2, group I, and the extrapancreatic PLA2, group
II – contribute to the raised activity. In contrast to the
group II-PLA2, the pancreatic PLA2 is heat-resistant for
1 hour at 60 °C. The catalytically inactive proenzyme of
the pancreatic PLA2 can be activated by trypsin. The
aim of our study was to evaluate the diagnostic value
of PLA2 isoenzyme activity measurements to identify
patients with severe complications in acute pancreatitis.
Blood samples from patients suffering from acute
pancreatitis were analyzed for catalytically active pancreatic
PLA2 on day 1 and 2 of hospitalization with a
modified radiometric Escherichia coli-based PLA2 assay.
In 10 of 41 patients clearly elevated values of catalytically
active, heat-resistant pancreatic PLA2 (7.2 to
81.2 U/l) were observed. This group of patients was
characterized by severe complications (necrotizing
pancreatitis, shock, sepsis, respiratory problems) of
which two patients subsequently died. Patients with
low or undetectable activity (<7 U/l) of pancreatic PLA2
recovered rapidly. According to these results the presence
of catalytically active pancreatic PLA2 in serum is
associated with severe complications of acute pancreatitis.
In contrast to total serum-PLA2, the catalytic
concentration of pancreatic PLA2 can serve as a prognostic
marker in acute pancreatitis.
Hyperhomocysteinemia is a risk factor for obstructive large-vessel disease. Here, we studied plasma concentrations of homocysteine and vitamins in patients suffering from subcortical vascular encephalopathy (SVE), a cerebral small-vessel disease leading to dementia. These results were compared to the homocysteine and vitamin plasma concentrations from patients with cerebral large vessel disease and healthy control subjects.
Plasma concentrations of homocysteine, vascular risk factors and vitamin status (B6, B12, folate) were determined in 82 patients with subcortical vascular encephalopathy, in 144 patients with cerebral large-vessel disease and in 102 control subjects. Patients with SVE, but not those with cerebral large-vessel disease, exhibited pathologically increased homocysteine concentrations in comparison with control subjects without cerebrovascular disease. Patients with SVE also showed lower vitamin B6 values in comparison to subjects without cerebrovascular disease. Logistic regression analysis showed that homocysteine is associated with the highest risk for SVE (odds ratio 5.7; CI 2.5–12.9) in comparison to other vascular risk factors such as hypertension, age and smoking.
These observations indicate that hyperhomocysteinemia is a strong independent risk factor for SVE.
The S-100B protein is released by injured astrocytes.
After passage through a disintegrated blood-brain barrier
(BBB) the molecule can be detected in the peripheral
circulation. We investigated the association
between the extent of brain injury and S-100B concentration
in serum in cerebral injury caused by cerebral
ischemia and cerebral fungal infection.
Study I: The S-100B serum concentration was serially
determined in 24 patients with ischemic stroke at
4, 8, 10, 24, 72 hours after the onset of symptoms. We
observed that patients with brain lesions larger than 5
cm3 exhibited significantly increased serum levels of
S-100B at 10, 24 and 72 hours compared to those with
lesion volumes below 5 cm3. Furthermore, an association
between S-100B serum concentration and neurological
outcome was observed.
Study II: In a mouse model of systemic fungal infection
with Candida albicans we observed that serum
levels of S-100B increased at day 1 after intravenous
infection. At this time we could histologically demonstrate
brain tissue injury by invading hyphae which
had crossed the BBB. Furthermore, reactive astrogliosis
was demonstrated by immunohistochemistry. On
day 7 we found a significant decrease of S-100B serum
level compared to day 1 and 4. This was associated
with a demarcation of the fungi with leukocytes in
brain tissue at this late phase of infection. No further
invasion through the BBB was seen on day 7.
In conclusion, serum levels of S-100B reflect the
time course of tissue injury in cerebral ischemia and
cerebral infection to a similar extent. Thus, S-100B
may be a useful marker to assess cerebral tissue injury.