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Biomedical subjects

J P Seguela

Publications and source records attributed to J P Seguela.

At least 19 recordsLinked to original sources

Inhibitory activity of anti-interleukin-4 and anti-interleukin-10 antibodies on Toxoplasma gondii proliferation in mouse peritoneal macrophages cocultured with splenocytes from infected mice.

Cocultures of splenocytes from Toxoplasma gondii-immunized mice or from naive mice, separated by a transwell membrane from naive macrophage layers, induced a decrease in T. gondii proliferation in macrophages in comparison with cultures without splenocytes or cocultures with splenocytes from infected mice. Interleukin 4 (IL-4) and IL-10 levels increased in cocultures of splenocytes from infected mice with naive macrophages. In contrast, the levels of these cytokines decreased in cocultures with splenocytes from immunized mice. No correlation was found between the release of interferon-gamma (IFN-gamma) and the inhibition of parasite multiplication. Cocultures with splenocytes from immunized mice induced an increase in tumor necrosis factor-alpha (TNF-alpha) levels. In contrast, in cocultures with splenocytes from infected mice, TNF-alpha production decreased. In cocultures with splenocytes from infected mice, T. gondii proliferation in macrophages was neutralized by anti-IL4 or anti-IL10 antibodies and was associated with increased TNF-alpha production. Moreover, this study demonstrates the significant combined effect of IL-4 and IL-10 on the down-regulation of macrophage-effector functions. A soluble positive signal was given by splenocytes to induce the production of TNF-alpha by macrophages. This signal was inhibited by IL4 and IL10. This process is biologically relevant in the regulation of T. gondii proliferation.

Animals↗

Prevalence of drugs of abuse in urine of drivers involved in road accidents in France: a collaborative study.

The collaborative, anonymous, case-control study was intended to determine the prevalence of opiates, cocaine metabolites, cannabinoids and amphetamines in the urine of drivers injured in road accidents and to compare these values with those of non-accident subjects ("patients") in France. Recruitment was performed nationwide in the emergency departments of five hospitals and comprised 296 "drivers" aged 18 to 35 and 278 non-traumatic "patients" in the same age range. Females represented 28.4% of "drivers" and 44.2% of "patients." Screening for drugs in urine was performed by fluorescence polarization immunoassays in each center. Each positive result was verified using gas chromatography-mass spectrometry (GC-MS), in a single laboratory. Statistical analysis comprised single-step logistic regression and simultaneously took account of confounding factors and the final differences in prevalence values between the two populations or different subgroups. Cannabinoids were found in 13.9% of drivers (16.0% of males and 8.3% of females, p < 0.05) and 7.5% of patients (12.3% of males, 1.6% of females, p < 0.0001); only in females was this prevalence higher in injured drivers than in patients (p < 0.05). Opiates were present in 10.5% of drivers' and 10.4% of patients' urine samples (NS), and were more frequent in urine samples positive for cannabinoids, in drivers (p < 0.01) as well as in patients (p < 0.001). The prevalence of cocaine metabolites in drivers and patients was 1.0 and 1.1% and that of amphetamines 1.4 and 2.5%, respectively. No causal relationship between drugs and accidents should be inferred from this retrospective study. Nevertheless, the high prevalence of cannabis and opiate (licit or illicit) use in young people, whether injured drivers or patients, has potential implications for road traffic safety in France. Cocaine and amphetamines did not appear to be a major problem, unlike the experience in other countries.

Accidents, Traffic↗

The evolution of ocular toxoplasmosis in anti-interferon gamma treated mice.

PURPOSE: A clinico-histopathological cross correlation was made to study the mechanism of tissue damage in toxoplasmic retino-choroiditis during an experimental reactivation of chronic toxoplasmosis and to compare the influence of treatment by sulfadiazine on the retinal lesions. METHODS: Chronically infected Swiss-Webster mice were treated, six weeks after infection, with an avirulent strain of Toxoplasma gondii (Beverley strain) with polyclonal rabbit antibody directed against murine interferon gamma. RESULTS: Mice treated by anti-interferon gamma developed clinical lesions between day 5 and day 30 (lesions including single foci of retinochoroiditis, multifocal lesions or diffuse areas of retinal necrosis). These lesions did not arise from borders of pre-existing scars. The retina was photographed with an operating microscope fitted with a 90 diopter lens. Biological study showed a significant rise of parasitic loads in the eye and brain. Histological examination is in favour of free organism dissemination via retinal vessels; the lesions are restricted to the inner retina and ciliary body, the parasites migrated from extra-ocular cysts via the vasculature. No cysts were seen at the beginning of the study; they were found at the scar phase and appeared in mice treated with sulfadiazine. The clinical lesions were not caused by cysts but by coagulated necrosis in the retinal tissue. Parasite migration may have played a trigger role. CONCLUSIONS: The retinal damage was constituted either as a result of a toxic effect of the organisms or as a hypertensive reaction to the toxoplasma organism. The results of this study showed that the treatment with anti interferon gamma was sufficient to reactivate chronic infection.

Adrenal Cortex Hormones↗

[Efficacy and tolerance of praziquantel (Biltricide) in the treatment of distomatosis caused by Fasciola hepatica].

OBJECTIVES: Due to the side-effects of dehydroemetine, we have chosen praziquantel, a broad-spectrum antihelmintic, as a treatment for distomatosis secondary to Fasciola hepatica in humans. The aim of this retrospective study was to evaluate the efficacy and tolerance to praziquantel in patients with this disease. METHODS: Twenty-five patients (12 men) with a definite diagnosis of distomatosis and no previous treatment were followed-up between 8 months and 3 years (> 18 months in 76% of cases). The follow-up was based on clinical, biochemical and serological criteria. All patients received praziquantel (75 mg/kg/day orally) for 5 days. Treatment was started after endoscopic or surgical removal of parasites locolized in the biliary tract, in two patients. A similar therapeutic course was administered twice in four patients with persistent clinical symptoms, hypereosinophilia or arch 2 on immunoelectrophoresis. RESULTS: Cumulative rates of patients with normalized eosinophilia and seronegativation at 6, 9 and 12 months were 55, 65, 75% and 55, 70, 100%, respectively. Complete recovery occurred in 18 patients (72%) whereas hypereosinophilia persisted for more than one year in 5 patients. No side-effects, except transient nausea in a few cases, were observed. CONCLUSION: Since praziquantel seems to be both effective and well tolerated in a large proportion of patients, this drug can be recommended as a first choice for distomatosis due to Fasciola hepatica in human.

Adult↗

Kinetics study and characterisation of target excreted/secreted antigens of immunoglobulin G, M, A and E antibodies from mice infected with different strains of Toxoplasma gondii.

A kinetics study and characterisation of target excreted/secreted antigens of immunoglobulin (Ig) G, M, A and E antibodies were realised by Western blotting with immune sera of mice inoculated with three strains of Toxoplasma gondii: RH, C56 and S3. IgG antibodies of the immune sera recognised the major proteins of the three excreted/secreted antigen preparations with molecular masses of 30, 45, 63 and 77 kDa. IgM antibodies recognised proteins revealed by IgG antibodies but with variable intensities; some proteins were revealed during a short period. IgA antibodies did not recognise the 35-kDa antigen or the antigens inferior to 28 kDa. The RH excreted/secreted antigens were revealed with the highest intensity. The IgE antibodies were briefly detected in trace amounts during period from the 20th to the 35th day. The RH strain with its excreted/secreted antigens had the best antigenicity and is a good model for immunoprotection studies.

Animals↗

New in vitro assay based on glucose consumption for determining intraconazole and amphotericin B activities against Aspergillus fumigatus.

We developed a new in vitro method of evaluating antifungal molecules. Fungal growth was determined by measuring glucose consumption, the only carbon source in a synthetic medium. First, the growth of 12 Aspergillus fumigatus strains was studied. Glucose consumption was an excellent indicator of fungal growth. Second, the partial inhibition of growth was calculated in terms of the 90% or 50% inhibitory concentration for the 12 strains after treatment with itraconazole and amphotericin B. With a 3-day incubation time, the calculated 90% and 50% inhibitory concentrations agreed with those obtained by a macromethod and with those reported in previous publications. In each case the high degrees of efficacy of itraconazole and amphotericin B against A. fumigatus were confirmed. Partial inhibition induced by low concentrations of antifungal agents was quantifiable by this new method.

Amphotericin B↗

Eicosanoid production by mouse peritoneal macrophages during Toxoplasma gondii penetration: role of parasite and host cell phospholipases.

The metabolism of endogenous arachidonic acid by mouse resident peritoneal macrophages infected in vitro with Toxoplasma gondii was studied. Prelabeling of macrophages with [5,6,8,9,11,12,14,15-3H]arachidonic acid and challenge with tachyzoites for 15 min resulted in a high mobilization of free labeled arachidonic acid (178%) in the culture medium. The parasites also triggered the synthesis of 6-keto-prostaglandin F1 alpha (47%), prostaglandin E2 (44%), leukotrienes C4 and D4 (33%) and 5-, 12-hydroxyeicosatetraenoic acids (155%). The study indicated that during the intracellular development phase of the parasites, 6-keto-prostaglandin F1 alpha (38%), prostaglandin E2 (31%) leukotrienes C4 and D4 (15%), hydroxyeicosatetraenoic acids (43%), and free arachidonic acid (110%) were secreted into the culture medium. Pretreatment of tachyzoites with phospholipase A2 inhibitors (4-p-bromophenacyl bromide and quinacrine) and no calcium in the culture medium resulted in inhibition of tachyzoite penetration into the macrophages and a decrease of the arachidonic acid metabolism. The triggering of the arachidonic acid cascade by T. gondii was dependent on the active penetration of the parasites into the macrophages, whereas preincubation of the macrophages with phospholipase A2 inhibitors did not affect penetration or free arachidonic acid release, thereby supporting a role for parasite phospholipase in the penetration process and in arachidonic acid mobilization from macrophage membrane phospholipids. Moreover, treatment of macrophages with phospholipase A2 inhibitors decreased the activities of the cyclooxygenase and lipoxygenase pathways, also suggesting an activation of host cell phospholipase A2 by the parasite.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Toxoplasmosis in the Republic of Senegal. Sero-epidemiological survey].

The presence of Toxoplasmosis in Senegal was investigated by the detection of IgG antibodies. 415 samples were obtained from healthy subjects from different regions of the country. In subjects of over 30, a greater number were found positive for IgG antibodies if they lived in a humid climate (25% in Northern Senegal, 57.7% in eastern Senegal). In Dakar 33.3% of the pregnant women studied had antibodies. This study confirms the presence of Toxoplasmosis in Senegal.

Adolescent↗

[Toxoplasmosis in the Central African Republic. Complementary study in a rural area].

The epidemiological survey on the incidence of toxoplasmosis in rural areas of Central African Republic was carried out on a healthy population. The 814 samples came from 5 regions with 4 different climates. About 40% of the adults had IgG antibodies against Toxoplasma gondii except in pre-desert area where only 25% were positive. Girls became positive earlier than boys, but there was no difference between adult men and women except in pre-desert zone where men were more positive.

Adolescent↗

[Toxoplasmosis in the Congo Republic. Seroepidemiological study].

Our study group, which was composed of over 2,500 subjects, aged between 0 and 65 years, came from different regions of Congo. The samples obtained were examined for the presence of IgG and IgM against Toxoplasma gondii. IgG were detected in about 33% of children over 9 years and in about 40% of adults. A study of IgM confirmed the early contact of children with the parasite (11% of positive samples for children between 4 and 9) and that of young women (5 to 7% positivity for subjects between 15 and 30). In spite of local variations, the extremely humid climate did not allow us to detect a difference based on the origin of the samples as furthermore there seems to be an ethnic factor involved. Among the different types of professions in our sample only farmers appear to be less frequently positive. Diet, as well as contact with animals do not seem to have an influence.

Adolescent↗

[Epidemiological study of toxoplasmosis at Kinshasa and in lower Zaire].

An epidemiological survey of human toxoplasmosis was carried out in urban Kinshasa and in rural Kwilu-Ngongo (Bas-Zaïre). First contact with Toxoplasma gondii occurred earlier in children from Kinshasa, but adults aged over 30 were more often carriers of IgG antibodies in Kwilu-Ngongo (65.5%) compared to those in Kinshasa (50.2%). In Zaire, nutritional diet and telluric contact seem to be very important.

Adolescent↗

[Epidemiology of toxoplasmosis in Ivory Coast].

The purpose of this study was to determine the prevalence of toxoplasmosis in samples of healthy populations in Ivory Coast. Various factors have been studied: age, sex, ethnic group, occupation, food, contacts with animals, climate. The samples were obtained in four places which were different by geographical situation and climate: Abidjan (urban site), Bonoua (littoral site), Bin-Houye (forest site), Odienne (predesert site). The samples of sera or blood were deposited on filter-papers and tested by latex agglutination (for IgG) and ISAGA (for IgM). Results were analysed by statistical methods. More than 2,000 samples have been studied, showing a prevalence higher in humid tropical zones (55.6% to 70%) than in predesert zone (37.2%). The first contact of the child with the parasite was more often before reaching 10 years but the risk for women was important until the age of 20. The other studied factors didn't appear to have any effect.

Adolescent↗

Enhancing resistance and modulation of humoral immune response to experimental Candida albicans infection by patulin.

Mice receiving patulin (10 mg/kg) from 1 to 4 days showed enhancing resistance to intraperitoneal challenge with 10(8) viable Candida albicans at day 2. Resistance to C. albicans infection (10(6) blastospores) appeared to be unchanged after cyclophosphamide oral administration (60 mg/kg). Immunoglobulins levels (IgA, IgM, IgG) are marked depressed (10 to 75%) in mice infected and/or treated by patulin and cyclophosphamide. The results show that an increase of neutrophil count may be among the factor underlying the late increase in resistance to C. albicans after administration of patulin.

Animals↗

[Enhancement of resistance of mice Toxoplasma gondii by 2 polysaccharides beta 1-3, beta 1-6 (PSAT and Scleroglucan)].

The protective effect of PSAT and Scleroglucan (beta 1-3, beta 1-6 polysaccharides), has been studied in mice infected with different strains of Toxoplasma gondii (RH, attenuated RH or Prugniaud strains). Intramuscular or intravenous administration of PSAT before infection of mice by the attenuated RH strain, resulted in a significant enhancement of survival: 100% of survival in the treated group, compared to 33% in controls and 50% in mice pretreated with Scleroglucan (10 mg/kg, intravenously). In contrast, there was no difference in the survival rate between the group treated with PSAT (1 mg/kg, IV) and the control in mice infected with the virulent RH strain: all mice died between day 7 and day 8. In mice infected with 15 cysts of the Prugniaud strain a decrease in the chemiluminescence (CL) of peritoneal macrophages and of the number of cysts in the brain of mice were observed in mice treated either with PSAT (1 mg/kg, IM) or scleroglucan (10 mg/kg, IM).

Adjuvants, Immunologic↗

Immunological analysis of the aqueous humour in candida endophthalmitis. II: Clinical study.

An anterior chamber paracentesis was carried out on six patients with candida endophthalmitis and on control subjects. We endeavoured to find out if there was local production of antibodies by evaluating the anti-candida antibody titres, the immunoglobulin G, and the albumin levels in the aqueous humour and in the serum. A significant difference in the level of specific antibodies between patients and controls was found. Local synthesis of anti-candida antibodies was discovered in five out of six patients with candida endophthalmitis. There would seem to be a correlation between the severity of uveitis and antibody titres.

Adult↗

[Comparison of protein concentrations in saliva and serum].

Saliva and serum protein profiles composed of 12 proteins: IgA, IgG, IgM, albumin, transferrin, alpha 1-glycoprotein acid, alpha 2-macroglobulin, alpha 1-proteinase inhibitor, haptoglobine, C3C, C4 and CRP were obtained by laser nephelometry of aliquots of samples of non-stimulated whole saliva and blood taken at the same time. The population of 138 controls of both sexes was divided into 4 age groups: 1 (20 to 29 years), 2 (30 to 39 years), 3 (40 to 49 years), 4 (50 to 60 years). Using the techniques developed for saliva assay, 10 proteins were measurable: IgA, IgG, IgM, albumin, transferrin, alpha 1-glycoprotein acid, alpha 2-macroglobulin, alpha 1-proteinase inhibitor, haptoglobulin and C3C. The C4 fraction and CRP were present at concentrations lower than the detection limit i.e. at 1.8 and 2.05 mg/l. In the serum 11 proteins were analysed, CRP occurring at less than 0.01 g/l. The statistical two-factor variance analysis test (sex and age) demonstrated the statistically significant influence of age in the saliva for alpha 1-PI and alpha 2-M in the serum for Tf, alpha 2-M and alpha 1-PI, and sex in the serum for IgG, IgM, alpha 1-PI, alpha 2-M and also the interaction of both factors in the serum for alpha 2-M.

Adult↗