Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus

<p>Abstract</p> <p>Background</p> <p>Avian influenza virus (AIV) is classified into two pathotypes, low pathogenic (LP) and high pathogenic (HP), based on virulence in chickens.</p> <p>Differences in pathogenicity between HPAIV and LPAIV might eventually be related to specific characteristics of strains, tissue tropism and host responses.</p> <p>Methods</p> <p>To study differences in disease development between HPAIV and LPAIV, we examined the first appearance and eventual load of viral RNA in multiple organs as well as host responses in brain and intestine of chickens infected with two closely related H7N1 HPAIV or LPAIV strains.</p> <p>Results</p> <p>Both H7N1 HPAIV and LPAIV spread systemically in chickens after a combined intranasal/intratracheal inoculation. In brain, large differences in viral RNA load and host gene expression were found between H7N1 HPAIV and LPAIV infected chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and LPAIV could infect cultivated embryonic brain cells, but in accordance with the absence of the necessary proteases, replication of LPAIV was limited. Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens only. In intestine, where endoproteases that cleave HA of LPAIV are available, we found minimal differences in the amount of viral RNA and a large overlap in the transcriptional responses between HPAIV and LPAIV infected chickens. Interestingly, brain and ileum differed clearly in the cellular pathways that were regulated upon an AI infection.</p> <p>Conclusions</p> <p>Although both H7N1 HPAIV and LPAIV RNA was detected in a broad range of tissues beyond the respiratory and gastrointestinal tract, our observations indicate that differences in pathogenicity and mortality between HPAIV and LPAIV could originate from differences in virus replication and the resulting host responses in vital organs like the brain.</p

Developmental delays and dental caries in low-income preschoolers in the USA: a pilot cross-sectional study and preliminary explanatory model

Abstract Background Anecdotal evidence suggests that low-income preschoolers with developmental delays are at increased risk for dental caries and poor oral health, but there are no published studies based on empirical data. The purpose of this pilot study was two-fold: to examine the relationship between developmental delays and dental caries in low-income preschoolers and to present a preliminary explanatory model on the determinants of caries for enrollees in Head Start, a U.S. school readiness program for low-income preschool-aged children. Methods Data were collected on preschoolers ages 3–5 years at two Head Start centers in Washington, USA (N = 115). The predictor variable was developmental delay status (no/yes). The outcome variable was the prevalence of decayed, missing, and filled surfaces (dmfs) on primary teeth. We used multiple variable Poisson regression models to test the hypothesis that within a population of low-income preschoolers, those with developmental delays would have increased dmfs prevalence than those without developmental delays. Results Seventeen percent of preschoolers had a developmental delay and 51.3% of preschoolers had ≥1 dmfs. Preschoolers with developmental delays had a dmfs prevalence ratio that was 1.26 times as high as preschoolers without developmental delays (95% CI: 1.01, 1.58; P < .04). Other factors associated with increased dmfs prevalence ratios included: not having a dental home (P = .01); low caregiver education (P < .001); and living in a non-fluoridated community (P < .001). Conclusions Our pilot data suggest that developmental delays among low-income preschoolers are associated with increased primary tooth dmfs. Additional research is needed to further examine this relationship. Future interventions and policies should focus on caries prevention strategies within settings like Head Start classrooms that serve low-income preschool-aged children with additional targeted home- and community-based interventions for those with developmental delays

Association between clinical parameters and the presence of active caries lesions in first permanent molars Associação entre parâmetros clínicos e a presença de lesões ativas de cárie em primeiros molares permanentes

The aim of the present study was to evaluate the association between clinical parameters and the presence of active caries lesions on the occlusal surface of first permanent molars. Forty eight children (5.8-13.8 years-old) with at least one first permanent molar present were selected. The clinical parameters evaluated were gender, age, DMF-T and dmf-t, presence of active white spots in other teeth, general plaque index, tooth's dental arch (upper or lower), tooth's side (right or left), presence of visible plaque and eruption degree of the first permanent molars. The first permanent molars were evaluated through visual inspection by two examiners in order to assess the presence of active or inactive caries lesions on the occlusal surface. Univariate and multivariate analyses for determination of the association between clinical parameters and the presence of active caries lesions in these teeth were performed. The presence of active white spots in other teeth was associated with the presence of active caries lesions in the first permanent molars, in both univariate and multivariate analyses (Odds ratio = 8.8 and 1.9, respectively). The presence of abundant visible plaque on the occlusal surface of the first permanent molars (Odds ratio = 3.5 in the univariate analysis, and 3.9 in the multivariate one) also presented a significant association. In conclusion, the presence of active white spots in other teeth and the presence of considerable visible plaque were associated with the presence of active caries lesions on the occlusal surfaces of first permanent molars.<br>O objetivo do presente trabalho foi avaliar a associação entre parâmetros clínicos e presença de lesões ativas de cárie sobre a superfície oclusal de primeiros molares permanentes. Quarenta e oito crianças (5,8-13,8 anos) com pelo menos um primeiro molar permanente foram selecionadas. Os parâmetros clínicos avaliados foram sexo, idade, CPO-D e ceo-d, presença de manchas brancas ativas em outros dentes, índice de placa, arco dentário do dente (superior ou inferior), lado do dente (direito ou esquerdo), presença de placa visível e grau de erupção dos primeiros molares permanentes. Os primeiros molares permanentes foram avaliados usando inspeção visual por dois examinadores para avaliar a presença de lesões de cárie ativas ou inativas sobre a superfície oclusal. Análises univariada e multivariada para avaliação da associação dos parâmetros clínicos e presença de lesões ativas nesses dentes foram realizadas. A presença de manchas brancas ativas em outros dentes apresentou associação significante com a presença de lesões ativas de cárie nos primeiros molares permanentes, em ambas as análises univariada e multivariada ("Odds ratio" = 8,8 e 1,9, respectivamente). A presença de placa visível abundante sobre a superfície oclusal dos primeiros molares permanentes ("Odds ratio" = 3,5 na análise univariada, e 3,9 na análise multivariada) também apresentou associação significante. Em conclusão, a presença de manchas brancas ativas em outros dentes e a presença de placa visível abundante apresentaram associação com a presença de lesões ativas de cárie sobre a superfície oclusal dos primeiros molares permanentes