BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

A method combining morphological, immunocytochemical and chromosomal examinations of the same cell in the study of lymphoproliferative diseases

6 cases of different lymphoproliferative diseases were studied with the new MAC (Morphology-Antibody-Chromosome) method in order to find out 1) if the abnormal karyotype is confined to the monoclonal cell population, 2) if there are, within this clone, also cells with a normal karyotype, and 3) if the method can help the pathologist to diagnose malignant lymphoproliferative diseases. The MAC method allows a simultaneous study in the same metaphase cell of the karyotype, surface markers, and some morphological features. In all cases in which a monoclonal cell proliferation was detected immunohistologically, the MAC examination showed a chromosomal abnormality for the same light chain as was detected in immunohistology, but not in other cells. In all but a single case, all mitotic cells belonging to the clonal cell proliferation had an abnormal karyotype. In this case with lambda clonality, 2/8 lambda-positive mitoses had a normal karyotype. However, all the normal mitoses occurred in small lymphocytes whereas the abnormal mitoses were seen in large blastic cells. In 1 case, the MAC method helped in confirming the diagnosis of malignant lymphoma (nodular small cleaved cell type). Especially in lymphomas composed of a mixed cell population, the MAC method makes it possible to find out which cell types have an abnormal karyotype and which have a normal karyotype.     

Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.     

Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI

Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T₁-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker ^99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose. In vitro Gd-DOTA was stable at a pH > 2 with < 2% dissociation at 24 h during incubation with HCI. Dissociation during incubation with HCI was linearly dependent on H⁺ concentration (0.77 < pH < 2.02). Less Gd-DOTA was absorbed onto the solid phase than ^99mTc-DTPA (25% cf 36%). in vivo Gd-DOTA marked gastric contents provided strong positive contrast. Similar emptying curves were observed with both MRI and double-indicator techniques (r = 0.987, P < 0.001). Gd-DOTA has the potential to be a useful liquid phase contrast agent in MR studies on gastric function.     

Differences in a K current in schwann cells from normal and neurofibromatosis-infected damselfish

Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K⁺ current (K current), with a strong dependence on the Nernst potential for K⁺. This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (K_d ? 1 mM) and by dendrotoxin (15 μM) but were insensitive to extracellular tetraethyammonium (≤ 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of ?40 mV, while in tumored cells this average was 12%, a significant difference. © 1994 Wiley-Liss, Inc.     

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.     

Ganglioglioma: A clinicopathological study of 10 cases

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto-medial, bifrontal, temporal, temporo-basal, temporo-parieto-occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki-67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio- and chemotherapy is still controversial.     

Persistent platelet activation in patients with type 2 diabetes treated with low doses of aspirin

BACKGROUND: The percentage of diabetic patients who do not benefit from the protective effect of aspirin is larger than in other populations at cardiovascular risk. OBJECTIVE: We compared the ability of aspirin to suppress TxA2 and platelet activation in vivo, in type-2 diabetics vs. high-risk non-diabetic patients. METHODS: Urinary 11-dehydro-TXB2, plasma sCD40 L, and sP-selectin were measured, together with indices of low-grade inflammation, glycemic control, and lipid profile, in 82 patients with type-2 diabetes and 39 without diabetes, treated with low doses of aspirin. RESULTS: Urinary 11-dehydro-TxB2, plasma sCD40L and sP-selectin were significantly higher in diabetics than in controls: [38.9 (27.8-63.3) vs. 28.5 (22.5-43.9) ng mmol(-1) of creatinine, P = 0.02], [1.06 (0.42-3.06) vs. 0.35 (0.22-0.95) ng mL(-1); P = 0.0001], [37.0 (16.8-85.6) vs. 20.0 (11.2-35.6) ng mL(-1), P = 0.0001], respectively. The proportion of individuals with diabetes increased across quartiles of 11-dehydro-TxB2, sCD40L, and sP-selectin, with the highest quartiles of 11-dehydro-TxB2, sCD40L and sP-selectin, including 66%, 93.3%, and 93.3% of individuals with diabetes. Markers of platelet activation positively correlated with indices of glycemic control but not with markers of low-grade inflammation. CONCLUSIONS: Platelet dysfunction associated with insufficient glycemic control, may mediate persistent platelet activation under aspirin treatment.