Regulation of peritoneal and systemic neutrophil-derived tumor necrosis factor-alpha release in patients with severe peritonitis: role of tumor necrosis factor-alpha converting enzyme cleavage

OBJECTIVE: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-alpha production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-alpha production and TNF-alpha converting enzyme (TACE) expression by PMN in the blood and peritoneum of patients with severe peritonitis. DESIGN: A prospective study. SETTING: A surgical adult intensive care unit in a university hospital. PATIENTS: A total of 29 consecutive immunocompetent patients with severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a diffuse secondary peritonitis. Thirteen volunteers served as controls. MEASUREMENTS: Blood and peritoneal fluid recovered during laparotomy were analyzed and compared for 1) soluble TNF-alpha, soluble L-selectin, and type I and II TNF-alpha receptor levels; 2) PMN membrane TNF-alpha, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-alpha production by cultured PMN. Correlations between these forms of PMN-derived TNF-alpha and the severity of the peritonitis and patient's outcome were investigated. MAIN RESULTS: Elevated soluble TNF-alpha levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-alpha and TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF receptors were highly released, suggesting also the role of TACE. In contrast, the capacity of both blood and peritoneal PMN to synthesize TNF-alpha in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-gamma), was impaired as compared with controls' blood PMN. Regulation of PMN-derived TNF-alpha was similar in the two compartments, but responses were more pronounced in the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated with the Sequential Organ Failure Assessment score and vital outcome. CONCLUSION: These human data demonstrate that mTACE is up-regulated at the PMN surface during severe peritonitis. This finding could be related to a paracrine regulatory loop involving some TACE substrates such as TNF-alpha, L-selectin, and TNF receptors.     

Occurrence of putative virulence genes in arcobacter species isolated from humans and animals

Interest in arcobacters in veterinary and human public health has increased since the first report of the isolation of arcobacters from food of animal origin. Since then, studies worldwide have reported the occurrence of arcobacters on food and in food production animals and have highlighted possible transmission, especially of Arcobacter butzleri, to the human population. In humans, arcobacters are associated with enteritis and septicemia. To assess their clinical relevance for humans and animals, evaluation of potential virulence factors is required. However, up to now, little has been known about the mechanisms of pathogenicity. Because of their close phylogenetic affiliation to the food-borne pathogen Campylobacter and their similar clinical manifestations, the presence of nine putative Campylobacter virulence genes (cadF, ciaB, cj1349, hecA, hecB, irgA, mviN, pldA, and tlyA) previously identified in the recent Arcobacter butzleri ATCC 49616 genome sequence was determined in a large set of human and animal Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii strains after the development of rapid and accurate PCR assays and confirmed by sequencing and dot blot hybridization.     

Fifteen years' experience in scorpion envenomation control in Algeria

In Algeria, scorpion envenomation is real public health problem. Since the creation of the National Committee of Control of Scorpion envenomations (CNLES), several steps have been taken to deal with this problem. After a brief historical introduction, we present the main elements of the action carried out both in terms of treatment and of prevention of scorpion proliferation. The epidemiological situation is presented by stressing the difficulties involved in collecting reliable data. We also address the question of citizen and stakeholder awareness since public participation is crucial in all prevention programmes. Training for healthcare providers is also one of the principal axes of the Committee's programme which includes national, regional, and even local seminars. We describe the improvement of production and research on venoms carried out by the Institute Pasteur of Algeria. We conclude by discussing the action plan for 2001 and prospects for an enhanced strategy in the fight against the scorpion envenomation.     

Quantitative ultrasonic tissue characterization as a new tool for continuous monitoring of chronic liver remodelling in mice.

BACKGROUND/AIM: Recognition of the limitations of liver biopsies has led to the need for non-invasive tests to assess liver fibrosis from intensity and kinetic point of views. The aim of the present study was to evaluate non-invasive ultrasonic tissue characterization for the continuous monitoring of this process in mice. METHODS: Twelve-week-old male and female C57Bl6/J mice were submitted to repetitive carbon-tetrachloride (CCl4) intraperitoneal injections during 8 weeks or analysed 28 days after common bile duct ligation (BDL). The extent and kinetic of the disease progression were followed by the measurement of ultrasound backscatter intensity. This was compared with histological and blood parameter analysis. RESULTS: CCl4 induced a progressive increase in in vivo liver tissue backscatter intensity in both males and females. This increase was mainly correlated with interstitial fibrosis and, to a lower extent, with nuclear surface of the hepatocytes. A similar result was found after BDL. CONCLUSIONS: These data demonstrate for the first time in a systematic study that ultrasound tissue characterization can be used as a reliable tool to follow liver remodelling in mice continuously.     

The neuroanatomy of Eml1 knockout mice,a model of subcortical heterotopia

The cerebral cortex is a highly organized structure responsible for advanced cognitive functions. Its development relies on a series of steps including neural progenitor cell proliferation, neuronal migration, axonal outgrowth and brain wiring. Disruption of these steps leads to cortical malformations, often associated with intellectual disability and epilepsy. We have generated a new resource to shed further light on subcortical heterotopia, a malformation characterized by abnormal neuronal position. We describe here the generation and characterization of a knockout (KO) mouse model for Eml1, a microtubule‐associated protein showing mutations in human ribbon‐like subcortical heterotopia. As previously reported for a spontaneous mouse mutant showing a mutation in Eml1, we observe severe cortical heterotopia in the KO. We also observe abnormal progenitor cells in early corticogenesis, likely to be the origin of the defects. EML1 KO mice on the C57BL/6N genetic background also appear to present a wider phenotype than the original mouse mutant, showing additional brain anomalies, such as corpus callosum abnormalities. We compare the anatomy of male and female mice and also study heterozygote animals. This new resource will help unravel roles for Eml1 in brain development and tissue architecture, as well as the mechanisms leading to severe subcortical heterotopia.     

Air pollution: a new respiratory risk for cities in low-income countries.

Since the major accidents that occurred in the 1960s, air pollution has commonly been considered as a respiratory risk factor whose effects are most often studied in industrialised countries. Our aim is to show that it is now the turn of low- and middle-income countries to take this risk factor into account. After a discussion of the characteristics of air pollution, how it is diffused and the main known health effects (short- and long-term effects), we describe the specific differences between the cities in the North and the South. As a result of late industrialisation, cities in the South are now faced with pollution from industrial sources and urban traffic with polluting vehicles. The case of Algeria and Morocco illustrates this situation and its potential health risks. In order to prevent the health risks of air pollution in the cities of the South, systems for measuring pollution levels and epidemiological surveillance need to be put in place rapidly. This strategy can only work if it is supported by a strong partnership from industrialised countries.     

Sahara honey shows higher potency against Pseudomonas aeruginosa compared to north Algerian types of honey

Six varieties of honey from different regions in Algeria were used to determine their potency against Pseudomonas aeruginosa. Four varieties originated from northern Algeria, and two from the Sahara. Three types of media were used. On nutrient agar the minimum inhibitory concentration (MIC) of the four northern varieties ranged between 30% (vol/vol) and 31% (vol/vol), while the MIC of the Sahara varieties was 11% (vol/vol) and 14% (vol/vol). On King A agar the MIC of the four northern varieties ranged from 25% (vol/vol) to 31% (vol/vol), whereas the MIC of the two varieties of Sahara honey was 12% (vol/vol) and 15% (vol/vol). On nutrient broth the MIC of the northern varieties ranged from 10% (vol/vol) to 21% (vol/vol), whereas the MIC of the two varieties of Sahara honey was 9% (vol/vol). The botanic flora of Sahara is known in Algeria for its medicinal uses, and thus the higher potency of the Sahara honey is most probably due to antibacterial substances in its plant derivates. These findings suggest that Sahara honey could be used for managing wounds and burns, which are mostly infected by P. aeruginosa.     

Effect of Cleome arabica Leaf Extract on Rat Paw Edema and Human Neutrophil Migration

The anti-inflammatory activity of Cleome arabica leaf extract was studied in vivo and in vitro. Firstly, the extract was examined for its anti-inflammatory activity using carrageenan-induced rat paw edema as a model of acute inflammation. A subplantar injection of 0.1 ml of carrageenan 1% induced a progressive swelling of the rat paw in all time points, that reached a maximal volume in placebo group within 5 h. Results showed that pre-treatment of rats by Cleome arabica leaf extract, 1 h prior the injection of the phlogogenic agent, prevented the increase of the edema in dose-dependent manner with an ED 50 of 231 mg/kg, body weight. The extract doses 100, 200 and 300 mg/kg, reduced edema to 65.54 ± 5.2%, 57.86 ± 8%, and 41.54 ± 3.6%, respectively, 5 h after the carrageenan injection. Secondly, we have examined the effect of Cleome arabica leaf extract on human neutrophil migration induced by fMLP (10 -7 M), using 48-well chemotaxis chamber. Results showed that the extract inhibited neutrophil chemotaxis significantly (p < 0.01) and in a dose-dependent manner. Neutrophil migration was reduced to 16.71 ± 4.6% in presence of 50µg/ml of Cleome arabica leaf extract. It appears that the antiinflammatory activity of Cleome arabica leaf extract, observed in vivo as well as in vitro, could be due to its high flavonoid content (19%). These results may contribute to explain the use of this plant in folk medicine.     

Impact of calcium and vitamin D therapy on arterial and cardiac disease in young adults with childhood-onset end stage renal disease.

Sir, In the discussion of their well-documented study on cardiovasculardisease in young adults with childhood-onset of end-stage renaldisease (ESRD), the Berlin paediatricians Briese et al. [1]pointed out interesting differences with a quite similar studyreported 4 years ago by their colleagues of Heidelberg [2]:the prevalence of coronary calcifications (10 vs 92%) and ofcardiac valve calcifications (0 vs 32%) was quite lower in theBerlin study than in the Heidelberg one, while the