Search PubMed⌕ Search

Biomedical subjects

S Harraga

Publications and source records attributed to S Harraga.

17 recordsLinked to original sources

Cystic echinococcosis in Algeria: cattle act as reservoirs of a sheep strain and may contribute to human contamination.

In Algeria, cystic echinococcosis (CE) is a serious economic and public health problem. The common sheep/dog cycle is usually considered as the major source of human contamination. But to date the main strain of Echinococcus granulosus involved in the human contamination and the role of other hosts are still unknown. This paper reports an original work performed in northern Algeria combining field observations and molecular analysis. In a first step, examination of 6237 carcasses in slaughterhouses showed high infection and fertility rates in cattle and dromedaries. Then, in a second step, we used a molecular biology approach to identify the E. granulosus strain(s) involved. Forty-six samples from various origins were collected. They were analysed using comparison of PCR-amplified DNA sequences with one genomic (BG 1/3) and two mitochondrial (COI and NDI) targets. Results show the presence of a "sheep" strain of E. granulosus in North Algeria circulating between cattle and ovines and infectious to humans, whereas in South Algeria, a "camel" strain and a "sheep" strain were found to circulate in camels and in sheep, respectively. This study also reports an ambiguous genotype which resembled the "sheep" strain genotype (Gl) on the basis of the partial COI gene sequence, whereas on the basis of the partial NDI gene sequence, it was similar either to the "sheep" strain (Gl) or to the "camel" strain (G6). Besides its basic interest, our study confirms the role of other hosts (mainly cattle) in leading to transmission to humans and suggests that control measures should not only target sheep.

Algeria↗

Polymorphisms of the TAP1 and TAP2 genes in human alveolar echinococcosis.

We postulated that TAP genes may influence the susceptibility of some individuals to Echinococcus multilocularis infection. Six coding region variants (codons 333 and 637 in TAP1, and 379, 565, 651 and 665 in TAP2) were typed in 94 patients and 100 controls. Thr/Thr homozygosity at TAP2/665 was more prevalent in patients than in controls [64% vs. 45%, respectively; odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.1; 2.7)] and Thr/Ala heterozygozity was less prevalent (32% vs. 50%, respectively) (P = 0.014). Of the 38 patients with progressive lesions, 76% were Thr/Thr, as compared with 55% of patients without progressive lesions and 45% of controls (P = 0.058 and 0.02, respectively), independent of HLA status. To determine whether this association is functionally relevant, functional analyses and/or confirmation in distinct populations of patients with alveolar echinococcosis would be required.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Interactions between landscape changes and host communities can regulate Echinococcus multilocularis transmission.

An area close to the Qinghai-Tibet plateau region and subject to intensive deforestation contains a large focus of human alveolar echinococcosis while sporadic human cases occur in the Doubs region of eastern France. The current review analyses and compares epidemiological and ecological results obtained in both regions. Analysis of rodent species assemblages within quantified rural landscapes in central China and eastern France shows a significant association between host species for the pathogenic helminth Echinococcus multilocularis, with prevalences of human alveolar echinococcosis and with land area under shrubland or grassland. This suggests that at the regional scale landscape can affect human disease distribution through interaction with small mammal communities and their population dynamics. Lidicker's ROMPA hypothesis helps to explain this association and provides a novel explanation of how landscape changes may result in increased risk of a rodent-borne zoonotic disease.

Animals↗

The effect of ginkgo biloba extract on free radical production in hypoxic rats.

In the present study, we assayed the antioxidant properties of Ginkgo biloba (Gb) extract on rats submitted to 21 d of chronic hypoxia. Doses of 25 and 50 mg/kg were examined. Oxygenated free radical production measured by the chemiluminescence technique was significantly decreased in treated rats compared to control rats placed in similar experimental conditions, and this effect was more significant at the 50 mg/kg dose. On the other hand, no antioxidant enzyme activities of the drug were observed towards red blood cells. These results suggest that ginkgo biloba extract has a free radical scavenging action. These antioxidant properties could explain the beneficial hematological properties of Gb extract.

Animals↗

An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China.

Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P<0.006), but not a history of red fox hunting (P>0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.

Adult↗

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions.

To clarify the role of Th1- and Th2-type cytokines in the various outcomes of human alveolar echinococcosis (AE), the cytokine immune response of self-cured patients was studied and compared with those of progressive AE patients and healthy subjects. Self-cured patients were divided into two groups according to the following clinical features: subjects who had positive Echinococcus multilocularis serologies and hepatic calcifications typical of AE were classified as 'abortive AE' patients, and those who had positive E. multilocularis serologies but no hepatic lesions or calcifications detectable by ultrasonography were classified as 'positive serology' subjects. Secretions of IL-5, IL-10 and interferon-gamma, and expression of IL-5 mRNA were evaluated in peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen phytohaemagglutinin-C or specific E. multilocularis antigenic preparations. The cytokine profile of abortive AE patients was the opposite of that observed in progressive AE patients. An intermediate profile was observed in positive serology subjects. PBMC from abortive AE patients, whether non-stimulated or stimulated with PHA and antigenic preparations, secreted significantly lower levels of IL-10 than those isolated from progressive AE patients. Our observations seem to confirm the regulatory role of IL-10 in the immunopathology of human AE.

Animals↗

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype.

Differences have been shown between HLA characteristics of patients with different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2 haplotype was associated with more severe forms of this granulomatous parasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA-DR3+, DQ2+, B8+ AE patients and from 10 HLA-DR3-, DQ2-, B8- patients after non-specific mitogenic and specific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3+, DQ2+, B8+ healthy subjects and nine HLA-DR3-, DQ2-, B8- subjects were also studied as controls. PBMC from AE patients with HLA DR3+, DQ2+ haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients without this haplotype. Higher levels of IL-5 and IFN-gamma were also produced by these patients' PBMC after stimulation with non-purified parasitic antigenic preparations; however, the specific alkaline phosphatase antigen extracted from E. multilocularis induced only Th2-type cytokine secretion. A spontaneous secretion of TNF by HLA DR3+, DQ2+ B8+ AE patients was also found. These results suggest that HLA characteristics of the host can influence immune-mediated mechanisms, and thus the course of AE in humans; specific antigenic components of E. multilocularis could contribute to the preferential Th2-type cytokine production favoured by the genetic background of the host.

Animals↗

Red blood cell metabolism and hemoglobin oxygen affinity. Effect of vinburnine on normobaric hypoxic rats.

The influence of Vinburnine on red blood cell metabolism and hemoglobin oxygen affinity was investigated in normobaric rats (FiO2: 10%). Two periods of hypoxic exposure were performed (10-21 d). In each experimental series, rats were divided into two groups: Treated rats received a daily intraperitoneal injection of drug (4 mg/kg). Control rats in the same conditions of hypoxia received an isotonic saline solution. For a 10 d exposure period, Vinburnine does not affect red blood cell metabolism nor hemoglobin oxygen affinity. At 21 d period exposure, 2, 3 diphosphoglycerate (2, 3 DPG) and ATP amounts increase in treated rats. The rate of increase was 10% (p<0.05) and 28% (p<0.01), respectively. Red blood cell metabolism effect of Vinburnine was not accompanied by a modification in affinity hemoglobin oxygen (Hb-O2); no statistically significant difference was observed between treated rats and control rats concerning p50 (partial pressure oxygen at half hemoglobin saturation). Results suggest that Vinburnine has a metabolic effect corresponding to a glycolysis anaerobic stimulation, which can improve oxygen delivery to tissues and could explain the favorable hemoreological action of Vinburnine observed in a previous investigation.

Animals↗

Alteration in the production of free oxygen radicals and proinflammatory cytokines by peritoneal and alveolar macrophages in old mice and immunomodulatory effect of RU 41740 administration. Part I: Effect of short and repetitive noise stress.

The aim of this study was to analyze the effects of stress on natural immunity in old mice, and the potential of an immunomodulating drug to correct stress-induced immune abnormalities. We analyzed both the alveolar (ALM) and peritoneal macrophage (PerM) oxidative responses and cytokine productions of TNF-alpha and IL-1alpha, in old mice after exposure to 3 days of noise stress, with and without treatment with RU 41740, an immunomodulating compound. Production of Free Oxygen Radicals (FOR) by ALM and PerM macrophages was evaluated using a luminol-dependent chemiluminescence method at the basal state and after stimulation. Serum corticosterone was also measured. Three groups of 22-24 month-old C57BL/6 mice were studied. Seven mice were treated with RU 41740 (10 mg kg(-1)) every day for 5 days and then exposed to sound stress (110 dB, 1000 Hz, for 3 nights). Ten mice were treated with saline, then submitted to a sham stress. Eight animals received neither treatment nor stress. There was no difference in corticosterone level between the three groups and between these groups and a control group nonstressed, noncannulated. After stimulation by fMetLeuPhe, production of FOR by ALM and PerM significantly increased after stress and returned to normal values after RU 41740 treatment (p < 0.001). The cytokine levels (TNF-alpha and IL-1alpha) decreased after stress and returned to normal levels after RU 41740 treatment. This study shows that, in aged mice, auditory stress is associated with modifications of macrophage functions which are different, depending on their localization and on the function under study. It confirms the immunomodulatory capacities of RU 41740 that was shown to counteract these effects of stress in elderly animals.

Adjuvants, Immunologic↗

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

Animals↗

Increased basal production of interleukin-10 by peripheral blood mononuclear cells in human alveolar echinococcosis.

The secretion of IL-10 by peripheral blood mononuclear cells (PBMC) and the expression of IL-10 mRNA in fractionated CD4+ and CD8+ lymphocyte subsets and non-B-non-T cells, with and without stimulation by the mitogen phytohemagglutinin-C (PHA-C) and specific Echinococcus multilocularis (E. multilocularis) antigens, were assessed in 7 patients with alveolar echinococcosis (AE) and 6 healthy subjects. Results of studies on IL-10 were compared to those on IFN-gamma, IL-4 and IL-5 in the same patients and control subjects. IL-10 production was significantly higher in patient PBMC-culture supernatants than in the control group supernatants, both at the basal level and after mitogen or specific E. multilocularis antigen stimulation. Both CD4+ and CD8+ lymphocyte populations and non-B-non-T cells of AE patients and controls expressed IL-10 mRNA. Semi-quantification of IL-10 mRNA revealed a significantly higher transcript level in unstimulated-CD8+ T cells from AE patients in comparison with CD8+ T cells of healthy donors. PBMC from patients produced very low levels of IL-4 but the production of IFN-gamma was not significantly depressed compared to the controls. PBMC, isolated from 4 AE patients and 4 control subjects stimulated with specific E. multilocularis antigens, secreted IL-5; IL-5 mRNA was only detected in the CD4+ lymphocyte subset. The secretion of IL-5 and the expression of IL-5 mRNA in healthy subjects could be due to the presence of non-specific mitogenic parasitic factors. This non-specific mitogenic activity of the parasite, besides inducing a high secretion of IL-10 in patients with evolutive AE, may contribute to the lack of host control of parasite growth and to the persistence of granulomatous lesions, due to the inhibition of an efficient Th1 immune response.

Adult↗

Auditory stress induces changes in membrane functions of mouse peritoneal macrophages.

Stressful events induce responses in the endocrine and immune systems. The authors analysed the influence of repetitive noise stress on peritoneal macrophage oxidative and phagocytic responses. Plasma corticosterone levels were also measured. Different groups of 6- to 8-week-old C57BL/6 male mice were exposed for 1 night (n = 14) and 3 nights (n = 21) to a sound stress of 110 dB in an audiogenic stress chamber. Control animals were submitted to a sham stress for 1 night (n = 13) and 3 nights (n = 17). A marked decrease was observed in the phagocytic response to yeast (P = 3 x 10(-4)) while a mild increase in the oxidative response stimulated by opsonized zymosan was noted only after the 3 night stress (P = 0.02). Corticosterone levels of control and stressed mice did not differ. These results indicate that the stress resulting from repetitive noise causes modifications in peritoneal macrophage activity, and that these changes are dependent on the duration of stress. These functional alterations seem more complex than a simple general suppression or activation.

Animals↗

[Imidazo(2,1-b)thiazole XII derivatives. Synthesis and research of immunoactivity in vitro on human T lymphocyte of 3-aroylmethyl and 2-aroyl-3-methyl(aryl)-5,6-dihydroimidaz o(2,1-b)thiazoles].

To estimate the influence of aryl group position on the immunostimulant properties of imidazo[2,1-b]thiazole derivatives, several compounds were obtained and tested, versus tetramisole hydrochloride, on the mobilisation of CD2 receptor by human T lymphocyte. The synthesis use the action of monobrominated beta-diketones on the 2-mercaptoimidazoline. So, 1-aryl-4-bromobutane-1,3-diones lead to 3-aroylmethyl-5,6-dihydroimidazo[2,1-b]thiazoles 4. Same, 1-aryl-2-bromobutane-1,3-diones and 1,3-diaryl-2-bromopentane-1,3-diones give respectively 3-aroyl-2-methyl-5,6-dihydroimidazo[2,1-b]thiazoles 5 and 3-aroyl-2-aryl-5,6-dihydroimidazo[2,1-b]thiazoles 6. Better yields are obtained when the reaction presents two steps. The first one, realized in acetone at room temperature, leads to an intermediate S-substituted 4,5-dihydroimidazole which, in second step, is cyclized in imidazo[2,1-b]thiazole compound via an unisolated carbinolamine. This one explains the univocal formation of 5 derivatives and the feasible blending in case of 6. The immunoactivity of several imidazothiazoles 4, 5 and 6 is lower that them of 6-aryl substituted compounds and particularly that the levamisole which is the reference product in this series.

Adjuvants, Immunologic↗

Immunomodulatory agents: dioxothiadiazabicyclo[3.3.0]octanes and their 2-spiro derivatives.

A series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octanes and a series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octane 2-spiro derivatives were synthesized from L-(-)-R-cysteine ethyl ester in two steps. The synthetic route involved condensation of the amino acid with an appropriate aldehyde or ketone, then a further condensation of the resultant ethyl thiazolidine-4-carboxylate with an isocyanate or an isothiocyanate. The proliferative response to human lymphocyte mitogen (phytohemagglutinin) was used as a primary screening assay for most of the thiadiazabicyclic compounds in comparison with levamisole. Furthermore, the most active compounds were tested for ability to release soluble receptors (sRIL-2) after mitogenic stimulation of T cells and for ability to activate macrophage oxidative metabolism measured by chemiluminescence. Most compounds were active in all three tests and some showed dose-dependent activity.

Adjuvants, Immunologic↗

Studies on immunostimulating derivatives: synthesis of some pyrrolo[1,2-c]pyrimidines.

In a search for potential immunomodulating agents novel pyrrolo[1,2-c]pyrimidines were synthesized and their structures elucidated by spectroscopic means. Unfortunately, most of them were cytotoxic and devoid of effects on T lymphocyte lymphoblastic transformation. Furthermore, they were inactive in the locomotor activity test in mice.

Adjuvants, Immunologic↗

Effect of an auditory stress on peritoneal and alveolar cells in C57 BL/6J mice of advanced age.

The aim of this study was to analyse the effects of auditory stress on peritoneal and alveolar macrophages in C57 BL/6J mice of advanced age, and to compare the results to those obtained in old mice submitted to a sham stress, and to those observed in young mice submitted to the same auditory stress. We used a chemiluminescence assay to measure the production of free oxygen radicals (FOR) by macrophages. Eight 22 month-old mice were exposed to a sound stress of 110 dB for three consecutive nights; nine were submitted to a sham stress. The results were compared to those obtained in young (8 week-old) mice, 21 submitted to noise stress, and 17 controls. The corticosterone level was not increased after stress in any group. FOR production in old mice was significantly higher than that in young mice. Stress did not induce significant changes in FOR production by alveolar cells in young mice; however, the FOR production by alveolar cells was significantly higher in the stressed group than in the control group of old mice. These results show that noise stress is associated with modifications of macrophage functions that are influenced by cell localization, the behaviour of alveolar and peritoneal macrophages of old mice being clearly different in our experimental model.

Acoustic Stimulation↗