Influence of acetylsalicylic acid on a Listeria monocytogenes infection.

The influence of acetylsalicylic acid (ASA, CAS 50-78-2) on the Listeria monocytogenes infection in balb/c mice was investigated. One day prior to lethal or sublethal infection, balb/c mice were treated intravenously with therapeutic concentrations of ASA alone or ASA in combination with murine recombinant interferon gamma, a lymphokine produced by T-helper cells. Three days post-infection, parasite burdens of spleen and liver were determined by the colony-forming unit assay. It was shown that the prophylactic application of ASA in a concentration of 5 mg/kg body weight resulted in a more than 10-fold reduction of viable Listeria monocytogenes in spleen and liver of balb/c mice. In addition, the combination of a suboptimal dosage of interferon gamma with ASA resulted in a significantly higher survival rate compared to the untreated controls.

Morphology and histogenesis of squamous cell metaplasia of the rat lung after chronic exposure to a pyrolized pitch condensate and/or carbon black, or to combinations of pyrolized pitch condensate, carbon black and irritant gases.

Female Wistar rats were exposed to different concentrations of a pyrolized pitch condensate and/or carbon black particles and/or a combination of irritant gases for 18 hours/day, 5 days/week for 10 months, followed by a clean air period of up to 20 months. Bronchiolo-alveolar hyperplasia and squamous metaplasia were important components of the resulting lesions. Squamous metaplasia and associated hyperplasia was investigated by routine histology, scanning and transmission electron microscopy, and by immunohistochemical detection of various cytokeratins (CKs). Intensely CK positive squamous metaplasia lacking a distinct stratum spinosum was distinguishable from squamous metaplasia with a distinct stratum spinosum that reacted weakly CK positive or CK negative. The CK positive type was histologically characterized by narrow intercellular spaces, the weakly CK positive or CK negative type had markedly enlarged intercellular spaces. Differentiated hyperplastic epithelium and the normal lung parenchyma reacted CK negative. In poorly differentiated hyperplasia of the alveolar type associated with squamous metaplasia scattered cells with characteristics of squamous differentiation were detected. Ultrastructurally these cells showed increased amounts of filament bundles and immunohistochemically a positive reaction with the CK antibody. These cells were regarded as precursor stages of squamous metaplasia of the lung periphery in rats.

Immunotherapy of murine visceral leishmaniasis with murine recombinant interferon-gamma and MTP-PE encapsulated in liposomes.

The efficiency of immunotherapy with murine recombinant interferon-gamma (rIFN-gamma) in mouse visceral leishmaniasis caused by Leishmania donovani was examined. To avoid the side effects encountered after the in vivo administration of high dosages of free IFN-gamma, this lymphokine and muramyltripeptide (MTP-PE) were encapsulated into multilamellar liposomes. We established that a combination of 5 X 10(3) U of IFN-gamma and 6 micrograms of MTP-PE, encapsulated in liposomes and given i.v. in C56BL/6 and BALB/c mice activates macrophages from spleen and liver in vivo to kill L. donovani in vitro. Neither empty liposomes nor the same concentration of free IFN-gamma and/or MTP-PE injected i.v. resulted in a leishmanicidal activity of these macrophage populations. For verification of these results in an in vivo infection model, susceptible mice were infected with L. donovani and were treated with IFN-gamma and MTP-PE encapsulated in multilamellar vesicles. Treatment consisted of multiple i.v. injections beginning 4 and 2 days before infection (prophylactic), either simultaneously with the infection or at various times of the exacerbation and remission phases of visceral leishmaniasis. These mouse strains treated with IFN-gamma and MTP-PE in liposomes had significantly fewer splenic parasites than untreated mice or control animals treated with free drugs or empty liposomes. The targetting of multilamellar vesicles to liver and spleen make them particularly suited for the delivery of macrophage-activating substances used for treatment of visceral L. donovani infection.

Ultrastructural observations in hamster and rat lungs after chronic inhalation of cadmium compounds.

Long-term inhalation of CdCl2 at concentrations as low as 12.6 micrograms Cd/m3 causes development of lung tumors in rats (4). No information, however, was available on the chronic carcinogenicity of CdO, CdS and CdSO4 which are especially relevant to the occupational area. In the present joint study of the Fh-ITA and the Fh-IUCT, rats and hamsters were exposed to CdCl2, CdSO4, CdO and CdS in a chronic inhalation carcinogenicity set-up (2, 3). The goal of the ultrastructural investigation was to compare inflammatory reactions and fibrotic lesions, as well as epithelial alterations occurring in the species under study. The present communication focusses especially on observations obtained from male and female hamsters and rats chronically exposed to CdO. In addition, we report preliminary results from a short-term inhalation study with CdO.

Intestinal structural changes in African green monkeys after long term psyllium or cellulose feeding.

Intestinal structure of male adult African Green monkeys (Cercopithecus aethiops ssp vervets) was studied after 3 1/2 yr of consuming diets containing 10% psyllium husk or cellulose. Scanning electron microscopy (SEM) identified mild damage (cellular swelling and disarray, and microvillar denudation and disarray) at villous tips throughout the small intestine in the psyllium-fed monkeys. The cellulose group had similar duodenal damage. Differences were not found in colons by SEM. By light microscopy, jejunum had shorter villi with psyllium feeding, based upon villous height (P less than 0.05), and length around a sectioned villus (P less than 0.1), but not based upon the number of enterocytes per villus. Jejunal and ileal circular and longitudinal muscle layer thicknesses were increased in psyllium-fed monkeys. Colonic mucosal height was significantly (P less than 0.05) reduced and muscle layer thickness was mildly reduced in the psyllium-fed monkeys. Group differences were not found in intestinal weight or length or in the weight of small intestinal mucosal scrapings. Psyllium husk may cause epithelial cell loss and muscle layer hypertrophy in the jejunum and ileum and thinning of the colonic wall after prolonged feeding.