Protein Carbonyls in Bronchoalveolar Lavage Fluid in Mice, Rats and Hamsters Following Inhalation of Pigmentary Titanium Dioxide Particles.

Elevation of protein carbonyls has been implicated in the clinical setting as a result of oxidant damage associated with a number of disease states in both humans and laboratory animals. Protein carbonyls, the product of oxidative modification of amino acid residues, may result from macrophage and neutrophil inflammatory responses to inhaled particles. We hypothesized that increased levels of protein carbonyl groups in the bronchoalveolar lavage fluid (BALF) may serve as a biomarker of oxidative stress in rodents exposed to extremely high airborne concentrations of poorly soluble particles (PSP) of low toxicity. The objective of the present study was to compare the BALF protein carbonyl levels in three rodent species following a subchronic PSP exposure known to result in pulmonary pathology in chronically exposed rats under similar conditions. Female Fischer 344 rats, B6C3F1 mice, and Syrian golden hamsters were identically exposed by whole-body inhalation to concentrations of aerosolized pigmentary titanium dioxide (TiO2)(MMAD and GSD, 1.42 and 1.3 µm, respectively) for 6 h/day and 5 days/wk for 13 wk. Groups of animals were exposed to 0, 10, 50, or 250 mg/m(3) of pigmentary TiO2. Levels of protein carbonyl groups in BALF were measured at the termination of the 13-wk exposure with an ELISA assay utilizing a 2,4-dinitrophenylhydrazine fluorescent probe. Protein carbonyl levels were elevated in rats at both the mid and high dose (50 and 250 mg/m(3)), while in mice and hamster the levels were elevated only at the high dose (250 mg/m(3)). The elevations in protein carbonyl levels paralleled changes in BALF-associated cytologic and biochemical inflammatory indices, including total protein levels and neutrophil counts. Inflammatory changes in all three species were limited to animals exposed to the highest concentrations of particles. Rats were the only species tested that had coincidental elevation of both protein carbonyls and a high inflammatory response measured in BALF following the 50-mg/m(3) exposure. These results suggest that the measurement of protein carbonyl groups in BALF may be a useful biomarker of particle-induced oxidant change, although this endpoint should be used in conjunction with other oxidative endpoints as a total assessment of oxidant stress.

Comparison of Selected Pulmonary Responses of Rats, Mice, and Syrian Golden Hamsters to Inhaled Pigmentary Titanium Dioxide.

We present a preliminary report of a bioassay designed to compare and contrast selected pulmonary responses of female B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters to inhaled pigmentary titanium dioxide (TiO2). Animals were administered 10, 50, or 250 mg/m(3) TiO2 for 6 h/day and 5 days/wk, for 13 wk. Recovery groups were held for an additional 4-, 13-, or 26-wk period. Following exposure and at each recovery time, TiO2 burdens in the lung and lung-associated lymph nodes were determined. A separate group of animals was used at each time point to assess the inflammatory response of the lung by assaying total protein in bronchoalveolar lavage fluid (BALF) and cytologic examination of cells recovered in BALF. Burdens (mg/mg dry weight) of TiO2 in the lung following exposure to 10, 50, or 250 mg/m(3) TiO2 were 5.2, 53.5, and 170.2 for the mouse; 7.1, 45.1, and 120.4 for the rat; and 2.6, 14.9, and 120.3 for the hamster. With time after exposure, lung burdens of TiO2 particles were decreased and lymph-node burdens increased. Changes in the hamsters' burdens were more rapid than those in mice and rats. Increases in BALF cell numbers (macrophages and neutrophils) and in total protein were observed in all 3 species following exposure to 50 and 250 mg/m(3) TiO2, with the magnitude of response being the grea test in the rat. These responses remained elevated relative to control levels at 26 wk postexposure. Histopathologic examination of lungs showed a concentration-dependent retention pattern of particles that varied by species. Hypertrophy and hyperplasia of alveolar epithelium along with alveolar metaplastic and fibrotic changes were observed in rats exposed to 250 mg/m(3) TiO2. Alveolar epithelial proliferative changes were associated with inflammation in mice and hamsters, but the metaplastic and fibrotic changes noted in rats were not present in similarly exposed mice or hamsters. These data suggest that rats exposed subchronically to extremely high concentrations of pigmentary TiO2 differ from mice and hamsters in their cellular responses in the lung as well as in the way they clear and sequester particles. These differences may partly explain the differential outcome of pulmonary responses in various rodent species following chronic inhalation exposure to poorly soluble particles.

[Nosocomial septicemia and pseudobacteremia caused by Serratia marcescens]. / Septicémies nosocomiales et pseudo-bactériémies à Serratia marcescens.

An epidemiological survey was carried out which included a dual epidemic of septicaemia and pseudo-bacteremia caused by Serratia marcescens. The survey enabled 15 septicaemias and 43 pseudobacteremias to be detected in a regional hospital between March and August, 1983. Two mishandlings were at the origin of the outbreak: citrated tube normally reserved for coagulation tests were severely contaminated by Serratia marcescens, and inaccurate samplings had been made. Once the mechanisms of contamination were found, specific preventive measures put an end to the epidemic. The authors insist on the need for uncontaminated tubes and citrate solutions and for the development of precise sampling methods which are essential to avoid the occurrence of pseudo-bacteremia or septicaemia. It is important to detect such epidemics at an early stage by an efficient control of nosocomial infections, thus avoiding their extension.

[A single daily injection of ceftriaxone for treating suppurated meningitis in infants and children. Apropos of 31 cases]. / Injection quotidienne unique de ceftriaxone pour le traitement des méningites suppurées du nourrisson et de l'enfant. A propos de 31 cas.

Thirty-one infants and children aged 1 month to 15 years 3 months were treated with ceftriaxone once a day for the treatment of a meningitis related to Neisseria meningitidis (19 cases), haemophilus influenzae (7 cases), streptococcus pneumoniae (1 case), not identified bacteria (4 cases). All identified bacteria were sensitive to ceftriaxone. Twenty children were treated with 100 mg/kg/day, 11 with 50 mg/kg/day. CSF was sterile at the first control-generally performed 30 h after the onset of treatment-in all cases. Despite a great number of severe forms (fulminans purpura and septic shock; 11 cases; severe neurologic disturbances: 6 cases), all patients survived and recovered after a treatment of 9 to 22 days. Two infants exhibited neurologic sequelae: deafness, delayed development and hydrocephalus. Tolerance to ceftriaxone appeared to be good. With a 100 mg/kg/day dosage, mean CSF level at 6 h was 3.3 mg/l (0.8-7.7), on the first day of treatment. At the end of treatment, mean CSF level at 24h was 0.47 (0.15-2.5). With a 50 mg/kg/day dosage, mean CSF level at 6 h was 2,1 mg/l (1.1-3.9) in the first day of treatment. At the end of the treatment, mean CSF level at 24h was 0.22 mg/l (0.08-0.5). Once a day administration of ceftriaxone is adequate for the treatment of meningitis in infants and children. Though a 50 mg/kg/day dosage is probably sufficient in most cases, it seems to be more secure to use a 100 mg/kg/day dosage.

[Bacterial endocarditis due to Corynebacterium diphtheriae (author's transl)]. / Endocardite infectieuse à Corynebacterium diphtheriae.

A case of bacterial endocarditis with unusual features in a 5 year-old boy is reported. There was no underlying heart disease or provocating factor. The organism was a non toxigenic Corynebacterium diphtheriae which was difficult to classify. It appeared to be close to the JK group of Corynebacterium described by the Center for Disease Control and considered as possibly responsible for severe infections. However, it was sensitive to penicillin. The course of the disease was complicated by the destruction of coronary valves and by splenic infarctus. Replacement of the aortic valve with a prosthesis was necessary. The boy was finally cured but the outcome remains uncertain.