Association of synthetic anthelmintics and natural monoterpenes against Haemonchus contortus

The resistance of Haemonchus contortus to synthetic anthelmintics is an increasing concern and different strategies are being evaluated. The present trial studied the in vitro effect of the association of synthetic compound and natural monoterpene on eggs and larvae of H. contortus. The monoterpenes carvacrol, thymol, r-carvone, s-carvone, citral and p-cymene, and the synthetic antihelmintic ivermectin, and albendazole were used. Egg Hatch Test (EHT) and Larval Migration Inhibition Test (LMIT) were performed. The lowest efficient concentration of monoterpenes in EHT (≤ 11% of efficacy) and LMIT (≤ 18% of efficacy) was used in association with different concentration of synthetic compound. The IC50 and Synergism Rate (SR) were calculated. The highest efficiency of monoterpenes in EHT was obtained with r-carvone (IC50 = 0.25 mg/mL) and s-carvone (IC50 = 0.79 mg/mL) and in the LMIT with r-carvone (IC50 = 0.60 mg/mL). The best association was observed in the EHT with albendazol (thymol SR: 2.9 and r-carvone SR: 1.6) and ivermectin (citral SR: 1.9 and carvacrol SR:1.7). No synergistic effect was obtaining using the LMIT. The combination of synthetic compound and natural monoterpenes could be positive to gastrointestinal nematodes control: However this strategy should be carefully analysed due to the possibility of antagonic effects among the different compounds.Fil: Costa Junior, Livio. Universidade Federal do Maranhao; BrasilFil: Silva, Carolina R.. Universidade Federal do Maranhao; BrasilFil: Macedo, Sara R. D.. Universidade Federal do Maranhao; BrasilFil: Campos, Nagilla R. C. L.. Universidade Federal do Maranhao; BrasilFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina26th Conference World Association for the Advancement of Veterinary ParasitologyKuala LumpurMalasiaWorld Association for the Advancement of Veterinary Parasitolog

Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1)

Host cells respond to exogenous infectious agents such as viruses, including HIV-1. Studies have evaluated the changes associated with virus infection at the transcriptional and translational levels of the cellular genes involved in specific pathways. While this approach is useful, in our view it provides only a partial view of genome-wide changes. Recently, technological advances in the expression profiling at the microRNA (miRNA) and mRNA levels have made it possible to evaluate the changes in the components of multiple pathways. To understand the role of miRNA and its interplay with host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative global miRNA and mRNA microarray using human PBMCs infected with HIV-1. The PBMCs were derived from multiple donors and were infected with virus generated from the molecular clone pNL4-3. The results showed that HIV-1 infection led to altered regulation of 21 miRNAs and 444 mRNA more than 2-fold, with a statistical significance of p<0.05. Furthermore, the differentially regulated miRNA and mRNA were shown to be associated with host cellular pathways involved in cell cycle/proliferation, apoptosis, T-cell signaling, and immune activation. We also observed a number of inverse correlations of miRNA and mRNA expression in infected PBMCs, further confirming the interrelationship between miRNA and mRNA regulation during HIV-1 infection. These results for the first time provide evidence that the miRNA profile could be an early indicator of host cellular dysfunction induced by HIV-1

Neuronal apoptosis by HIV-1 Vpr: contribution of proinflammatory molecular networks from infected target cells

Background: Human immunodeficiency virus type 1 (HIV-1) induces neuronal dysfunction through host cellular factors and viral proteins including viral protein R (Vpr) released from infected macrophages/microglia. Vpr is important for infection of terminally differentiated cells such as macrophages. The objective of this study was to assess the effect of Vpr in the context of infectious virus particles on neuronal death through proinflammatory cytokines released from macrophages.Methods: Monocyte-derived macrophages (MDM) were infected with either HIV-1 wild type (HIV-1wt), Vpr deleted mutant (HIV-1{increment}Vpr) or mock. Cell lysates and culture supernatants from MDMs were analyzed for the expression and release of proinflammatory cytokines by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay respectively. Mitogen-activated protein kinases (MAPK) were analyzed in activated MDMs by western blots. Further, the effect of Vpr on neuronal apoptosis was examined using primary neurons exposed to culture supernatants from HIV-1wt, HIV-1{increment}Vpr or mock-infected MDMs by Annexin-V staining, MTT and Caspase - Glo® 3/7 assays. The role of interleukin (IL)-1β, IL-8 and tumor necrosis factor (TNF)-α on neuronal apoptosis was also evaluated in the presence or absence of neutralizing antibodies against these cytokines.Results: HIV-1{increment}Vpr-infected MDMs exhibited reduced infection over time and specifically a significant downregulation of IL-1β, IL-8 and TNF-α at the transcriptional and/or protein levels compared to HIV-1wt-infected cultures. This downregulation was due to impaired activation of p38 and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in HIV-1{increment}Vpr-infected MDMs. The association of SAPK/JNK and p38 to IL-1β and IL-8 production was confirmed by blocking MAPKs that prevented the elevation of IL-1β and IL-8 in HIV-1wt more than in HIV-1{increment}Vpr-infected cultures. Supernatants from HIV-1{increment}Vpr-infected MDMs containing lower concentrations of IL-1β, IL-8 and TNF-α as well as viral proteins showed a reduced neurotoxicity compared to HIV-1wt-infected MDM supernatants. Reduction of neuronal death in the presence of anti-IL-1β and anti-IL-8 antibodies only in HIV-1wt-infected culture implies that the effect of Vpr on neuronal death is in part mediated through released proinflammatory factors.Conclusion: Collectively, these results demonstrate the ability of HIV-1{increment}Vpr to restrict neuronal apoptosis through dysregulation of multiple proinflammatory cytokines in the infected target cells either directly or indirectly by suppressing viral replication. © 2012 Guha et al.; licensee BioMed Central Ltd

Comparative evaluation of human breast milk, bovine milk, and infant milk formula on cariogenicity in children: An in vivo study

Aim: The aim of the study was to compare the cariogenicity of human breast milk (HBM), bovine milk, and infant milk formulas. Patients and Methods: Ninety children of 1–4 years were randomly selected according to the type of milk they consume and were divided into five groups: Group I – HBM, Group II – cow milk, Group III – buffalo milk, Group IV – Lactogen 2, and Group V – Dexolac 4. Three parameters were assessed (salivary pH, plaque pH, and Streptococcus mutans count). Baseline salivary pH was measured, plaque sample was collected from children before feeding, and then, children were fed with milk. The second sample was collected after 45 min of feeding and the third sample after 3 h of second sample collection. Collected plaque samples were assessed for plaque pH and were sent to microbiological laboratory and cultured on blood agar. The intergroup comparison was done by one-way analysis of variance (ANOVA) and Tukey test. Intragroup comparison was done by one-way anova and Bonferroni test. P < 0.05 was considered statistically significant. Results: No statistically significant difference in intra- and intergroup comparisons of salivary pH was noted. However, with regard to plaque pH, there is a statistically significant difference in the second sample in Groups III, IV, and V. There was an increase in colony-forming units of S. mutans in plaque samples from baseline to the third sample in Groups IV and V. Conclusion: Lactogen 2 and Dexolac 4 showed greater cariogenic activity, buffalo milk is mildly cariogenic, whereas HBM and cow milk showed least cariogenicity