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J J Ballet

Publications and source records attributed to J J Ballet.

At least 19 recordsLinked to original sources

Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model.

OBJECTIVES: To evaluate the efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed Mongolian gerbil (Meriones unguiculatus) model. METHODS: Gerbils (1-month-old) were dexamethasone-immunosuppressed for 10 days and challenged orally with 10(5) Cryptosporidium parvum oocysts. From day 0 to day 12 post-infection, one group (n=14) was treated with 200 mg/kg/day nitazoxanide and another (n=15) with 100 mg/kg/day paromomycin. Infection and efficacy of nitazoxanide and paromomycin were assessed by measuring oocyst shedding in faeces, biliary tract and ileum histological examination. RESULTS: In nitazoxanide-treated and paromomycin-treated groups as compared with untreated animals (P<0.05), oocyst shedding was partially suppressed in a similar manner (P>0.05). Parasites were present in histological sections of the ileal mucosa of 16/16 infected untreated animals versus 3/14 and 6/15 in the nitazoxanide-treated and the paromomycin-treated groups, respectively (P<0.05). In addition, gall bladder infection was less frequent in nitazoxanide-treated (2/14, P<0.01) and paromomycin-treated (5/15, P=0.07) animals than in untreated controls (9/16). No histological alteration of biliary mucosa was observed in both treated and untreated infected gerbils. CONCLUSIONS: Present data support the efficacy of nitazoxanide and, to a lesser extent, paromomycin on biliary C. parvum infection in gerbils, and prompt further investigation of the potential clinical benefits of nitazoxanide in treating human biliary cryptosporidiosis.

Amebicides↗

Inhibitory activities of epidermal growth factor receptor tyrosine kinase-targeted dihydroxyisoflavone and trihydroxydeoxybenzoin derivatives on Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum development.

Several gene sequences of parasitic protozoa belonging to protein kinase gene families and epidermal growth factor (EGF)-like peptides, which act via binding to receptor tyrosine kinases of the EGF receptor (EGFR) family, appear to mediate host-protozoan interactions. As a clue to EGFR protein tyrosine kinase (PTK) mediation and a novel approach for identifying anticoccidial agents, activities against Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum grown in BM and HCT-8 cell cultures of 52 EGFR PTK inhibitor isoflavone analogs (dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives) were investigated. Their cytotoxicities against host cells were either absent, mild, or moderate by a nitroblue tetrazolium test. At concentrations ranging from 5 to 10 microg/ml, 20 and 5 analogs, including RM-6427 and RM-6428, exhibited an in vitro inhibitory effect of > or = 95% against at least one parasite or against all three, respectively. In immunosuppressed Cryptosporidium parvum-infected Mongolian gerbils orally treated with either 200 or 400 mg of agent RM-6427/kg of body weight/day for 8 days, fecal microscopic oocyst shedding was abolished in 6/10 animals (P of <0.001 versus untreated controls) and mean shedding was reduced by 90.5% (P of <0.0001) and 92.0% (P of <0.0001), respectively, higher levels of inhibition than after nitazoxanide (200 mg/kg/day for 8 days) or paromomycin (100 mg/kg/day for 8 days) treatment (55.0%, P of <0.001, and 17.5%, P of >0.05, respectively). After RM-6427 therapy (200 mg/kg/day for 8 days), the reduction in the ratio of animals with intracellular parasites was nearly significant in ileum (P = 0.067) and more marked in the biliary tract (P < 0.0013) than after nitazoxanide or paromomycin treatment (0.05 < P < 0.004). RM-6428 treatment at a regimen of 400 mg/kg/day for 12 days inhibited oocyst shedding, measured using flow cytometry from day 4 (P < 0.05) to day 12 (P < 0.02) of therapy, when 2/15 animals had no shedding (P < 0.0001) and 11/15 were free of gut and/or biliary tract parasites (P < 0.01). No mucosal alteration was microscopically observed for treated or untreated infected gerbils. To our knowledge, this report is the first to suggest that the isoflavone class of agents has the potential for anticoccidial therapy.

Animals↗

Kinetics of spleen and Peyer's patch lymphocyte populations during gut parasite clearing in Cryptosporidium parvum infected suckling mice.

Data from experimental and human cryptosporidiosis have established a major role of specific immunity in the control of Cryptosporidium parvum infection. In this work, alterations in spleen and Peyer's patch (Pp) lymphocytes were investigated in the course of a spontaneously resolutive gut cryptosporidiosis in four-day-old suckling NMRI mice infected with either 4 x 10(5) or 30 viable oocysts. Oocysts from entire small intestines, and spleen and Pp lymphocytes were examined using flow cytometry from day 7 to day 27 post-infection. Compared to uninfected animals, a 3-5 fold increase in the numbers of spleen TCR alphabeta+, CD4+, CD8+, TCR gammadelta+ and CD45R/B220+ lymphocytes was observed on day 17 post-infection in heavily infected animals. In Pp, more than ten-fold increases were observed, except for TCR gammadelta+ lymphocytes. At termination of infection, i.e. on days 21-23 after ingestion of 4 x 105 oocysts, T and B lymphocytes decreased rapidly in both organs, and remained lower than in uninfected animals on days 19-23 post-infection. In mice infected with 30 oocysts, similar alterations were observed in Pp, but not in spleen. Data suggest that in normally developing mice, clearance of gut C. parvum infection is associated with an initial increase in systemic and local lymphocyte numbers, followed by their decrease to below control levels during the recovery phase.

Animals↗

Association between chronic urticaria and thyroid autoimmunity: a prospective study involving 99 patients.

BACKGROUND: The association between chronic urticaria and thyroid autoimmunity has been a subject of debate. However, this link was suggested in studies searching thyroid microsomal antibodies (TMA), which are less sensitive and less specific than anti-thyroperoxidase antibodies, moreover these studies did not measure anti-TSH receptor antibodies, nor did they use a control group. As a consequence, the results of these studies are difficult to interpret. OBJECTIVE: The aim of this study was to determine whether chronic urticaria is statistically associated with thyroid autoimmunity. METHODS: In a prospective case-control study, we compared the frequency of thyroid autoantibodies in 45 patients with chronic urticaria and in 30 healthy adult volunteers; we also compared the frequency of chronic urticaria in 32 patients with thyroid diseases with thyroid autoantibodies and in 22 patients with thyroid diseases without thyroid autoantibodies. Thyroid autoantibodies and thyroid hormones were measured in all the subjects; antinuclear antibodies, rheumatoid factors, complement, IgE were assessed and routine laboratory tests were done in patients with chronic urticaria. Fisher's exact statistics were used to test our hypothesis. RESULTS: The frequency of thyroid autoantibodies was significantly higher in patients with chronic urticaria than in healthy controls (26.7%/3.3%; p < 0.01). All the patients with thyroid autoantibodies had thyroid hormone concentrations within the normal limits. The frequency of chronic urticaria was not significantly different (12.5%/9.1%; p = 0.7) in patients with thyroid diseases with or without thyroid antibodies. The rest of the biological investigations revealed only 1 patient with connective tissue disease. CONCLUSION: This study shows a significant association between chronic urticaria and thyroid autoimmunity, and that tests to detect thyroid autoantibodies are relevant in patients with chronic urticaria, whereas extensive laboratory tests are not.

Adolescent↗

Reactivity against Sarcocystis neurona and Neospora by serum antibodies in healthy French horses from two farms with previous equine protozoal myeloencephalitis-like cases.

Sarcocystis neurona is considered a leading cause of equine protozoal myeloencephalitis (EPM), a common infectious neurological disease in horses in the Americas. EPM-like cases associated with S. neurona peptide reactive antibodies in Western blots were recently described in Normandy, France. In this report, antibodies reacting with S. neurona merozoites were detected using an agglutination assay at titers ranging from 50 to 500 in sera from 18/50 healthy horses from two farms with a previous EPM-like case. Higher values were found in older animals. Four out of six horses which traveled or stayed in the US exhibited titers over 50, a higher figure than in the group which did not travel out of France or stayed in an other European country. No correlation was found between anti-S. neurona and anti-Neospora sp. antibody titers. Data prompt further study of significance of anti-S. neurona antibodies in clinically healthy or diseased European horses, and identification of putative immunizing parasite(s) and their host(s).

Animals↗

High prevalence of co-factor independent anticardiolipin antibodies in malaria exposed individuals.

Anticardiolipin antibodies (aCL) were investigated in 137 individuals chronically exposed to malaria and living in Africa and Asia. They belonged to several groups according to parasite (Plasmodium falciparum or vivax) and clinical manifestations (i.e. asymptomatic parasite carriers, acute uncomplicated attack or severe malaria episodes). aCL were measured in an enzyme immunoassay (ELISA) performed in the presence of either goat serum (aCLs) or gelatin (aCLg). In a group of 53 patients with autoimmune manifestations (i.e. antiphospholipid syndrome and/or lupus), detection of IgG but not IgM aCL was markedly reduced in the presence of gelatin. In malaria donors, high prevalence of serum co-factor-independent IgG and IgM were detected, and the presence of goat serum in the assay consistently decreased their detection. aCLg levels were found to be related to the clinical/endemic status of donors. IgG aCLg were found to be higher in asymptomatic P. falciparum carriers than in patients with uncomplicated acute or cerebral malaria. IgM aCLg were higher in the cerebral malaria group than in groups with uncomplicated acute malaria patients or asymptomatic individuals. Data suggest that using a serum co-factor independent, sensitive ELISA, aCL are commonly detected during malarial infections and related to malarial infection status.

Adolescent↗

Neosporosis in bovine dairy herds from the west of France: detection of Neospora caninum DNA in aborted fetuses, seroepidemiology of N. caninum in cattle and dogs.

Neospora caninum is considered one of the major causes of abortion in cattle in most parts of the world. In this study, the role of N. caninum was investigated in groups of aborted cattle and dairy herds from the west of France. Good correlation was found between parasite DNA detection in fetuses and serologic statuses of dams. In groups with documented abortion status and no antibodies to other pathogens, 17-45% of aborted animals were seropositive for N. caninum, and significant relationship between prevalence of Neospora antibodies and frequency of abortions was found. Neospora-associated abortions were observed all the year round, with a peak in summer. Higher ratios of seropositive abortions were found before the 6th month of gestation. In 12 herds studied in the field, serologic prevalence ranged 6-47%. No difference in age was found between seropositive and seronegative cows. Results indicate that N. caninum is an important and stable cause of abortion in cattle in France.

Abortion, Veterinary↗

Successful treatment of metronidazole- and albendazole-resistant giardiasis with nitazoxanide in a patient with acquired immunodeficiency syndrome.

A case of metronidazole- and albendazole-resistant giardiasis in a patient with the acquired immunodeficiency syndrome was successfully treated with nitazoxanide (1.5 g twice a day for 30 days). Animal studies and in vitro assays showed that the isolate was resistant to both metronidazole and albendazole and susceptible to nitazoxanide.

AIDS-Related Opportunistic Infections↗

Cryptosporidium parvum infection stimulates the secretion of TGF-beta, IL-8 and RANTES by Caco-2 cell line.

Cryptosporidium parvum is a common cause of diarrhea in humans. Although mild inflammatory mucosal infiltrate is usually observed, limited information is currently available on the pathogenic mechanisms involved in this phenomenon. The aim of this work was to investigate in vitro the influence of C. parvum infection on the secretion of lymphocyte-targeted chemokines (RANTES. MIP-1alpha, MIP-1beta, IL-8), proinflammatory cytokines (TNF-alpha, GM-CSF and IL-6) and TGF-beta by human enterocytic Caco-2 cells. C. parvum infection stimulates IL-8, RANTES and TGF-beta secretion by both the basal and apical side of caco-2 cells. A slight increase in TNF-alpha production by infected cells was observed in the apical compartment. Data suggest that enterocytic chemokines and/or TGF-beta are involved in the initiation and regulation of the mucosal response to C. parvum infection.

Animals↗

Efficacy of nitazoxanide, tizoxanide and tizoxanide glucuronide against Cryptosporidium parvum development in sporozoite-infected HCT-8 enterocytic cells.

The effects of nitazoxanide and its metabolites, tizoxanide and tizoxanide glucuronide, on the development of the asexual and sexual stages of Cryptosporidium parvum in differentiated human enterocytic HCT-8 cells were evaluated in a quantitative alkaline phosphatase immunoassay. Nitazoxanide, tizoxanide and tizoxanide glucuronide were inhibitory for up to 46 h when added after sporozoite invasion (MIC50 1.2, 22.6 and 2.2 mg/L, respectively). Tizoxanide had only limited activity, but nitazoxanide and tizoxanide glucuronide strongly inhibited asexual and sexual stages, respectively.

Animals↗

Metronidazole and albendazole susceptibility of 11 clinical isolates of Giardia duodenalis from France.

The metronidazole and albendazole susceptibility of 11 clinical isolates of Giardia duodenalis from France was determined using a neonatal mouse model and compared with the outcome in patients after standard metronidazole therapy (0.75 g/day for 5 days). All isolates found to be clinically resistant to metronidazole (4/11) exhibited an ID50 > 120 mg/kg in the mouse model. This therefore appears to be a suitable animal model in which to explore drug failures in human giardiasis.

Albendazole↗

Fetal distress increases interleukin-6 and interleukin-8 and decreases tumour necrosis factor-alpha cord blood levels in noninfected full-term neonates.

OBJECTIVE: To assess the influence of fetal distress on interleukin-1beta, interleukin-6, interleukin-8 and on tumour necrosis factor-alpha blood levels in noninfected full-term neonates. STUDY DESIGN: In a multicentre prospective study, cord blood samples were obtained at time of delivery from 234 noninfected full-term neonates for the purposes of measuring serum levels of interleukin-1beta, interleukin-6, interleukin-8 and tumour necrosis factor-alpha using immunoassays. Women were classified into four groups according to the mode of delivery (vaginal delivery or caesarean section) and the presence or absence of fetal distress. The role of labour was also investigated. RESULTS: No significant relationship was found between cytokine cord blood levels and the mode of delivery. Fetal distress was associated with an increase in interleukin-6 (P = 0.01) and interleukin-8 (P < 0.001) levels, and a decrease in tumour necrosis factor-alpha (P < 0.001). Labour was also associated with a significant increase in interleukin-6 and interleukin-8 cord blood levels (P = 0.01 and P < 0.001, respectively). CONCLUSION: Fetal distress and labour were each associated with elevated interleukin-6 and interleukin-8 cord blood levels in noninfected full term neonates while only fetal distress was associated with decreased tumour necrosis factor-alpha levels.

Delivery, Obstetric↗

Quantitative flow cytometric evaluation of maximal Cryptosporidium parvum oocyst infectivity in a neonate mouse model.

The importance of waterborne transmission of Cryptosporidium parvum to humans has been highlighted by recent outbreaks of cryptosporidiosis. The first step in a survey of contaminated water currently consists of counting C. parvum oocysts. Data suggest that an accurate risk evaluation should include a determination of viability and infectivity of counted oocysts in water. In this study, oocyst infectivity was addressed by using a suckling mouse model. Four-day-old NMRI (Naval Medical Research Institute) mice were inoculated per os with 1 to 1,000 oocysts in saline. Seven days later, the number of oocysts present in the entire small intestine was counted by flow cytometry using a fluorescent, oocyst-specific monoclonal antibody. The number of intestinal oocysts was directly related to the number of inoculated oocysts. For each dose group, infectivity of oocysts, expressed as the percentage of infected animals, was 100% for challenge doses between 25 and 1,000 oocysts and about 70% for doses ranging from 1 to 10 oocysts/animal. Immunofluorescent flow cytometry was useful in enhancing the detection sensitivity in the highly susceptible NMRI suckling mouse model and so was determined to be suitable for the evaluation of maximal infectivity risk.

Animals↗

Transcriptional and post-transcriptional mechanisms induce cyclin-D1 over-expression in B-chronic lymphoproliferative disorders.

Cyclin D1 participates in cell-cycle control, in the progression through the G(1) phase and in the transition from the G(1) to the S phase. The CCND1 locus, located in 11q13, is amplified and cyclin-D1 protein is over-expressed in a wide range of human solid tumors. In some B-lymphoid malignancies, the t(11;14)(q13;q32) translocation joins the Ig heavy-chain locus to the CCND1 locus and leads to cyclin-D1 over-expression. In this study, a series of 127 patients presenting a B-chronic lymphoproliferative disorder (B-CLPD) was analyzed using a competitive RT-PCR designed to detect cyclin-D1-mRNA over-expression. Cyclin-D1 mRNA was expressed in patients with mantle-cell lymphoma (MCL; 10/10), hairy-cell leukemia (HCL; 3/5), B-chronic lymphoid leukemia (B-CLL; 4/111) and B large-cell lymphoma (BLCL; 1/1). Densitometric analysis of RT-PCR products and Western-blot autoradiograms, in addition to cytogenetic data, indicated that activation of the cyclin-D1 gene occurred independently of the t(11;14)(q13;q32) translocation in patients with HCL. Indeed, a normal-sized protein of 36 kDa exhibiting a level incompatible with gene activation by a translocation mechanism was detected in lymphoid cells with a normal karyotype. Moreover, we found a discrepancy between cyclin-D1 mRNA and protein levels in MCL and B-CLL, which suggested that some regulatory mechanisms acting at a post-transcriptional level persist in tumor cells.

Adult↗

Enzyme immunoassay detection of Cryptosporidium parvum inhibition by sinefungin in sporozoite infected HCT-8 enterocytic cells.

Complete parasite development was obtained in differentiated human enterocytic HCT-8 cells infected at confluence with Cryptosporidium parvum sporozoites, and evaluated in a quantitative enzyme immunoassay. Forty-eight hours after infection, a linear correlation was found between optical density values and the number of parasites determined in an immunofluorescent assay. Sinefungin exerted an inhibitory effect when added within 4 h after sporozoite addition to HCT-8 cultures (MIC50 = 38 mumol L-1), while the inhibitory effects of paromomycin and pentamidine dimethanesulfonate were also easily detected (MIC50 = 0.87 mumol L-1 and 0.27 mumol L-1, respectively). Except for high pentamidine dimethanesulfonate concentrations, no alteration in optical microscopy morphology or trypan blue exclusion of HCT-8 cells was observed in the presence of anticryptosporidial agents, which suggests that they were primarily active against developing parasites. Data suggest that EIA detection of C. parvum development in sporozoite-infected HCT-8 cells provides an accurate and convenient model for in vitro evaluation of parasite infectivity, growth and response to anticryptosporidial agents.

Adenosine↗

Detection by the comet assay of apoptosis induced in lymphoid cell lines after growth factor deprivation.

Dysregulation of apoptosis contributes to various diseases such as neurodegenerative or aging disorders, autoimmune syndromes or cancers. Numerous experimental paradigms have been explored to characterize molecular and cellular modulators of apoptosis. Similarly, numerous techniques have been described for detecting and/or quantifying accurately cells committed to apoptosis. Besides the conventional techniques, we describe in this report that the comet assay, which detects DNA single- and double-strand breaks in situ, at the cellular level, is relevant for the characterization of apoptotic cells. The comet assay is very sensitive and detects DNA fragmentation occurring in the apoptotic process as early as exposure of phosphatidylserine residues on the outer leaflet. Thus the comet assay can be used for the recognition of apoptosis that follows the death signal caused, for example, by genotoxic stress as well as lack of survival signal as in growth factor deprivation.

Animals↗