Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance.     

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.     

Toxicity of the blue-green alga (cyanobacterium) Microcystis aeruginosa in drinking water to growing pigs,as an animal model for human injury and risk assessment

Hepatotoxins from blue-green algae are increasingly recognized as a potential hazard in drinking water supplies. The clinical consequences of ingestion include acute or chronic liver injury, with the possibility of enhanced susceptibility to, and growth of, liver tumors. To establish guidelines for water safety requires the demonstration of dose-dependent effects of toxicity and experimental determination of maximum “no-adverse-effect levels.” This paper describes the use of growing pigs as a model for human injury resulting from Microcystis toxins in drinking water. Risk assessment calculations using a series of safety factors are carried out, resulting in a guideline level after incorporating an additional safety factor for tumor promotion of approximately 1.0 μg toxins/L. With the Microcystis used for this trial, that concentration corresponds to 5000 cells/mL. © 1994 by John Wiley & Sons, Inc..     

Interleukin-1-inhibitor activity induced by respiratory syncytial virus: abrogation of virus-specific and alternate human lymphocyte proliferative responses

Respiratory syncytial virus (RSV) infection has been shown to induce human mononuclear leukocyte (MNL) production of net interleukin-1 (IL-1)-inhibitor activity. In the current studies of IL-1-inhibitor effects, RSV-exposed cells were compared with autologous MNL that were sham-exposed or exposed to inactivated RSV or influenza virus (which induces net IL-1 activity and commonly elicits effective homotypic immunity). Exposure of MNL to influenza virus or inactivated RSV resulted in increased expression of human leukocyte antigen-DR, the IL-2 receptor, and the transferrin receptor and increased progression through the cell cycle by 3 days. In contrast, exposure to infectious RSV resulted in decreased marker expression and cell cycle arrest, with abrogation of proliferation in response to the virus or other stimuli. These data raise the possibility that a contributing mechanism for recurrence of RSV infection is early suppression of the clonal expansion of virus-specific lymphocytes due to net IL-1-inhibitor activity.     

Varix node of the iris with spontaneous regression]

We report the findings in a 76-year-old woman who presented with a varix of the left iris that had manifested with hyphema. Slit lamp examination disclosed a circumscribed prominent round blood-filled lesion of the iris with smooth surface and surrounding hemorrhage. Examination with the laser flare-cell meter disclosed slightly increased flare of the left eye (10.2 photon counts/ms). Iris fluorescein angiography revealed a focal early circular hyperfluorescent area without leakage and a surrounding hypofluorescent area. Additionally, there was bilateral pseudoexfoliation. The iris varix showed complete regression during follow-up of two months. Possible etiological factors, including congenital or acquired changes of the iris vessels and alterations of the iris vessel walls in pseudoexfoliation syndrome, are discussed. Although varices of the iris are rare, they should be included in the differential diagnosis of prominent iris lesions.     

Articular histoplasmosis.

Rheumatic manifestations of histoplasmosis are uncommon. Polyarthritis or arthralgias may occur as a part of a sensitization process in primary acute histoplasmosis. Infectious arthritis may accompany disseminated histoplasmosis or occur as solitary monoarthritis. Treatment of the latter traditionally consists of surgical excision followed by amphotericin B. Reports of clinical experience with the newer triazole compounds in treating articular histoplasmosis are lacking. We describe a patient with solitary monoarticular histoplasmosis of the knee who was successfully treated with oral fluconazole and required no surgical intervention. Specific issues that pertain to clinical presentation and management of articular histoplasmosis are discussed.     

Septicaemia among neonates with tetanus.

In a study of 149 cases of neonatal tetanus (NNT) admitted into the University of Calabar Teaching Hospital, 49 (33 per cent) were also found to have septicaemia. The dominant organisms were coliforms and Staphylococcus aureus. A comparison of the clinical features of the septicaemic and non-septicaemic neonates showed umbilical cord infection to be an indicator of septicaemia. There was no significant difference in the case fatality rates of the two groups of patients and the overall case fatality was low (37 per cent). This is attributable to early diagnosis and treatment of the septicaemia cases. It is suggested that paediatricians should have a high index of suspicion of septicaemia among cases of NNT as a means of reducing case fatality.