Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune((R)) vaccine

In order to assess the immunotherapeutic potential on canine visceral leishmaniasis of the Leishmune (R) vaccine, formulated with an increased adjuvant concentration (1 mg of saponin rather than 0.5 mg), 24 mongrel dogs were infected with Leishmania (L.) chagasi. The enriched-Leishmune (R) vaccine was injected on month 6, 7 and 8 after infection, when animals were seropositive and symptomatic. The control group were injected with a saline solution. Leishmune (R)-treated dogs showed significantly higher levels of anti-FML IgG antibodies (ANOVA; p < 0.0001), a higher and stable IgG2 and a decreasing IgG I response, pointing to a TH1 T cell mediated response. The vaccine had the following effects: it led to more positive delayed type hypersensitivity reactions against Leishmania lysate in vaccinated dogs (75%) than in controls (50%), to a decreased average of CD4+ Leishmania-specific lymphocytes in saline controls (32.13%) that fell outside the 95% confidence interval of the vaccinees (41.62%, CI95% 43.93-49.80) and an increased average of the clinical scores from the saline controls (17.83) that falls outside the 95% confidence interval for the Leishmune (R) immumotherapy-treated dogs (15.75, CI95% 13.97-17.53). All dogs that received the vaccine were clustered, and showed lower clinical scores and normal CD4+ counts, whereas 42% of the untreated dogs showed very diminished CD4+ and higher clinical score. The increase in clinical signs of the saline treated group was correlated with an increase in anti-FML antibodies (p < 0.0001), the parasitological evidence (p = 0.038) and a decrease in Leishinania-specific CD4+ lymphocyte proportions (p = 0.035). These results confirm the immunotherapeutic potential of the enriched-Leishmune (R) vaccine. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog's potential infectiosity to phlebotomines. The enriched-Leishmune (R) vaccine was subjected to a safety analysis and found to be well tolerated and safe. (c) 2007 Elsevier Ltd. All rights reserved.

X-chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate

Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft palate group showing the most significant result (P=0.01). We did not find evidence for involvement of skewed XCI in the discordance for clefting in our sample of female MZ twins. However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate. (C) 2007 Wiley-Liss, Inc.

The karyotype of Cabassous unicinctus (Dasypodidae, Xenarthra)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Search for Genomic Alterations in Monozygotic Twins Discordant for Cleft Lip and/or Palate

Phenotypically discordant monozygotic twins offer the possibility of gene discovery through delineation of molecular abnormalities in one member of the twin pair. One proposed mechanism of discordance is postzygotically occurring genomic alterations resulting from mitotic recombination and other somatic changes. Detection of altered genomic fragments can reveal candidate gene loci that can be verified through additional analyses. We investigated this hypothesis using array comparative genomic hybridization; the 50K and 250K Affymetrix GeneChip (R) SNP arrays and an Illumina custom array consisting of 1,536 SNPs, to scan for genomic alterations in a sample of monozygotic twin pairs with discordant cleft lip and/or palate phenotypes. Paired analysis for deletions, amplifications and loss of heterozygosity, along with sequence verification of SNPs with discordant genotype calls did not reveal any genomic discordance between twin pairs in lymphocyte DNA samples. Our results demonstrate that postzygotic genomic alterations are not a common cause of monozygotic twin discordance for isolated cleft lip and/or palate. However, rare or balanced genomic alterations, tissue-specific events and small aberrations beyond the detection level of our experimental approach cannot be ruled out. The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance.

The effects of propolis on antibody production by laying hens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Uncaria tomentosa Aqueous-ethanol Extract Triggers an Immunomodulation toward a Th2 Cytokine Profile

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunization protected well nourished mice but not undernourished ones from lung injury in Methicillin-resistant Staphylococcus aureus (MRSA) infection

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Is the BCG Vaccine Safe for Undernourished Individuals?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both?

Ethnopharmacological relevance: Uncaria tomentosa (Willd.) DC (Rubiaceae) is a species native to the Amazon rainforest and surrounding tropical areas that is endowed with immunomodulatory properties and widely used around the world. In this study we investigated the immunomodulatory potential of Uncaria tomentosa (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes.Materials and methods: C57BL/6 male mice were injected with MLDS (40 mg/kg) and orally treated with UT at 10-400 mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and beta-cell insulin content were analyzed by HE and immunohistochemical staining, respectively, and measured by digital morphometry. Lymphocyte immunophenotyping and cytokine production were determined by flow cytometry analysis.Results: Treating the animals with 50-400 mg/kg of UT caused a significant reduction in the glycemic levels, as well as in the incidence of diabetes. The morphometric analysis of insulitis revealed a clear protective effect. Animals treated with UT at 400 mg/kg presented a higher number of intact islets and a significant inhibition of destructive insulitis. Furthermore, a significant protection against the loss of insulin-secreting presented beta-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400 mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in healthy animals. These same higher doses also increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the production of Th1 and Th2, with increased levels of IL-4 and IL-5.Conclusions: The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways. (C) 2011 Elsevier B.V. All rights reserved.

Developmental exposure to diuron causes splenotoxicity in male Sprague-Dawley rat pups

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Characterization and localization of dynein and myosins V and VI in the ovaries of queen bees

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Three-Dimensional Modelling of Honeybee Venom Allergenic Proteases: Relation to Allergenicity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effectiveness of ozonated water on Candida albicans, Enterococcus faecalis, and endotoxins in root canals

The aim of this study was to evaluate the effectiveness of ozonated water in the elimination of Candida albicans, Enterococcus faecalis, and endotoxins from root canals. Twenty-four single-rooted human teeth were inoculated with C. albicans and E. faecalis, and 24 specimens were inoculated with Escherichia coli endotoxin. Ozonated water (experimental group) or physiologic solution (control group) was used as irrigant agent. Antimicrobial effectiveness was evaluated by the reduction of microbial counts. Lipopolissacharide complex presence was assessed by limulus amebocyte lysate test and B-lymphocyte stimulation. Data were analyzed by Wilcoxon and Mann-Whitney tests (5%). Ozonated water significantly reduced the number of C. albicans and E. faecalis at the immediate sampling, but increased values were detected after 7 days. Ozonated water did not neutralize endotoxin. It could be concluded that ozonated water was effective against C. albicans and E. faecalis but showed no residual effect. No activity on endotoxin was observed.

B-cell lymphoblastic lymphoma in the maxilla of a child: A rare case report

Lymphoblastic lymphoma is a malignant neoplasia that originates from B or T lymphocyte precursors and rarely occurs in the mouth. The authors report a rare case of B-cell lymphoblastic lymphoma in the maxilla of a child. Clinical examination revealed facial asymmetry with a swelling of the right maxilla, covered by healthy mucosa and painful to palpation. Radiographic examination revealed a poorly defined radiolucent lesion. Based on the hypothesis of malignant neoplasia of hematopoietic origin, an incisional biopsy was performed. Histological examination revealed malignant neoplasia with proliferation of monomorphic, lymphoid cells. Immunohistochemical staining was positive for leucocyte common antigen (LCA), CD 10, CD20, CD79, and terminal deoxynucleotidyl transferase (TdT). After the diagnosis of B-cell lymphoblastic lymphoma, the patient underwent chemotherapy, but died of leukoencephalopathy and demyelinization caused by high doses of methotrexate.