Buchbesprechungen

Ohne Zusammenfassung     

Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in serum and urine of patients with onchocerciasis coinfected with intestinal nematodes and in urinary schistosomiasis

Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and O. volvulus- and S. haematobium-negative Guineans coinfected or infected with intestinal nematodes. The number of eosinophils and levels of eosinophil granule proteins but not of MPO were found to be strongly elevated in all Africans as compared to European controls. The highest serum ECP and serum and urinary EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda). Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher serum granule protein concentrations and/or absolute eosinophil counts and urinary ECP than those without nematode infections. Statistical differences between both sections were found for the absolute eosinophil counts and for serum EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda, indicating stimulation of the eosinophil potential of O. volvulus-positive patients by coexistent hookworm infection. This worm species, in contrast to A. lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE levels. From these results it is concluded that in nematode diseases, ECP and EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may, therefore, serve as parameters to monitor helminth infection. Urinary ECP may be a marker of eosinophiluria secondary to urogenital manifestation of S. haematobium. It is elevated in hyperreactive onchocerciasis activated by intestinal nematodes.     

Local nicotinamide therapy in erosive lichen of the oral mucosa]

The local treatment of erosive lichen planus by means of subfocal injections of nicotinamide has been successful in 19 of 25 cases. Nevertheless, it is no true alternative of the systemic chloroquine-triamcinolone treatment. A therapeutical program is presented in which the more riskful use of corticosteroids and chloroquine ranks but second.     

Transpapillary intraductal ultrasound in the evaluation of dominant bile duct stenoses in patients with primary sclerosing cholangitis

OBJECTIVE: Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma (CC) in approximately 9% of patients. Neither cholangiography nor endoscopic tissue sampling can reliably distinguish between CC and benign dominant bile duct stenosis. The aim of the present study was to assess the value of intraductal ultrasonography (IDUS) in distinguishing between benign and malignant dominant stenoses in PSC patients. MATERIAL AND METHODS: Forty PSC patients with dominant bile duct stenoses were studied prospectively. Transpapillary IDUS and endoscopic tissue sampling were performed in addition to endoscopic retrograde cholangiography (ERC). Cholangiography and IDUS findings were classified as malignant or benign by the investigators. Final diagnosis of malignant stenosis was based on positive histology and/or cytology, whereas a benign character was assumed in cases of negative tissue sampling and uneventful extended clinical follow-up. RESULTS: Eight PSC patients (20%) had dominant bile duct stenoses caused by CC, whereas 32 out of 40 patients (80%) had benign dominant bile duct stenoses. IDUS was significantly superior to ERC for detection of malignancy in terms of sensitivity (87.5% versus 62.5%, p=0.05), specificity (90.6% versus 53.1%, p<0.001), accuracy (90% versus 55%, p<0.001), positive predictive value (70% versus 25%, p<0.001), and negative predictive value (96.7% versus 85%, p=0.049). CONCLUSIONS: Transpapillary IDUS significantly increases the ability to distinguish malignant from benign dominant bile duct stenoses in patients with PSC.     

Regulation of enterocyte apoptosis by acyl-CoA synthetase 5 splicing

BACKGROUND AND AIMS: The constant renewal of enterocytes along the crypt-villus axis (CVA) of human small intestine is due to cell-inherent changes resulting in the apoptotic cell death of senescent enterocytes. The aim of the present study was to examine underlying molecular mechanisms of the cell death at the villus tip. METHODS: Characterization of human acyl-coenzyme A (CoA) synthetase 5 (ACSL5) was performed by cloning, recombinant protein expression, biochemical approaches, and several functional and in situ analyses. RESULTS: Our data show that different amounts of acyl-CoA synthetase 5-full length (ACSL5-fl) and a so far unknown splice variant lacking exon 20 (ACSL5-Delta 20) are found in human enterocytes. In contrast with the splice variant ACSL5-Delta 20, recombinant and purified ACSL5-fl protein is active at a highly alkaline pH. Over expression of ACSL5-fl protein is associated with a decrease of the anti-apoptotic FLIP protein in a ceramide-dependent manner and an increased cell-surface expression of the death receptor TRAIL-R1. Expression analyses revealed that the ACSL5-fl/ACSL5-Delta 20 ratio increases along the CVA, thereby sensitizing ACSL5-fl-dominated cells at the villus tip to the death ligand TRAIL, which is corroborated by functional studies with human small intestinal mucosal samples and an immortalized human small intestinal cell line. CONCLUSIONS: Our results suggest an ACSL5-dependent regulatory mechanism that contributes to the cellular renewal along the CVA in human small intestine. Deregulation of the ACSL5-fl/ACSL5-Delta 20 homeostasis in the maturation and shedding of cells along the CVA might also be of relevance for the development of intestinal neoplasia.