Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster

The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and β-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture

Dentinogenesis imperfecta in Osteogenesis imperfecta type XI in South Africa: a genotype–phenotype correlation

BACKGROUND: The maxillofacial and dental manifestations of Osteogenesis imperfecta (OI) have significant implications in terms of management. Although the occurrence of abnormal dentine in some forms of OI is well documented, there is scant information on the association of abnormal dentine in the Black African persons with phenotypic OI III and genotypic OI XI in South Africa. METHODS: This was a cross-sectional analytic study. A series of 64 Black South African individuals with a confirmed phenotypic diagnosis of OI III, ages ranging from 3 months to 29 years, were assessed clinically, radiographically, and at a molecular level. RESULTS: A total number of 64 saliva samples were analyzed and 3 DNA variations were identified in exon 5 of the FKBP10 gene. The homozygous mutation, c.[831dupC]; [831dupC], was identified in 23 affected persons who had no clinically obvious features of DI in their primary and secondary teeth. Radiologically, mild features of DI were evident in 10 persons in whom radiographic images were obtained and were given a Clinical–radiological score of 2. A compound heterozygous mutation, c. [831delC]; [831dupC], was identified in three siblings. An intraoral examination of these affected persons revealed no clinically apparent features of DI in their primary and secondary teeth. Due to the lack of radiological facilities, the presence or absence of DI could not be confirmed or negated. A second compound heterozygous mutation, c.[831dupC]; [1400-4C>G], was identified in a female of 29 years belonging to the Xhosa linguistic group. Her teeth appeared clinically normal but it was not possible to obtain radiographs. In 37 affected individuals, no disease-causing mutations were identified. CONCLUSION: Black African individuals in SA with the homozygous mutation in the FKBP10 gene have clinically unaffected teeth yet exhibited radiographic features of DI to varying degrees. This characterization is suggestive of a relationship between the genetic abnormality and the clinical manifestations of DI. The authors suggest that this diagnosis must include teeth that are clinically and/or radiologically aberrant, and should not exclude the presence of other, milder, dentinal aberrations associated with OI. There was no correlation between severity of OI and DI in this cohort of individuals

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

BACKGROUND: alpha/beta-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5[prime] regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients

The compatibility of denture cleansers and resilient liners Influência dos agentes químicos de limpeza sobre reembasadores resilientes de próteses

PURPOSE: Difficulty in cleaning resilient denture liners remains a material disadvantage. The purpose of the present study was to evaluate the effect of denture cleansers on hardness of resilient liner materials. MATERIALS AND METHODS: Three resilient liners, Luci Sof® (Dentsply), Molloplast-B® (Dentax), and Sofreliner® (Tokuyama), and two denture cleansers, Efferdent® (Warner-Lamber), and 0.5% alkaline hypochlorite preparation were used. Twenty specimens of each material were prepared, measuring 25X15X3mm. Two denture cleansing approaches were used: 1) alkaline hypochlorite, for 20 minutes; 2) alkaline peroxide, for 30 minutes. This procedure was repeated 8 times a day, during 90 days. The specimens were evaluated before and after 360 and 720 cycles, to simulate 1 and 2 years of clinical cleaning procedures, respectively. The Shore A hardness was evaluated in a durometer (Teclock GS-709A), with a penetrating load of 10N for 1 second. Any macroscopic changes, such as loss of color or alteration in surface texture were recorded by one observer. All numeric data were subject to ANOVA with repeated measures followed by Tukey's test (alpha= 0.05). RESULTS: All materials were significantly different, independently to time and treatment. Initially, Luci Sof® and Sofreliner® immersed in either hypochlorite or peroxide increased the hardness mean values significantly. These hardness mean values decreased significantly after 720 cycles. Molloplast-B® showed no significant difference after the treatments, in any time. CONCLUSIONS: Denture cleansers had no effect on hardness of the resilient denture liners evaluated after 2 years of in vivo simulated conditions of hygiene. Sofreliner® was the smoothest material before and after all treatments.<br>PROPOSIÇÃO: A maior desvantagem dos materiais reembasadores resilientes é a dificuldade em mantê-los limpos. Esse trabalho avaliou o efeito de agentes de limpeza sobre a dureza de reembasadores resilientes. MATERIAL E MÉTODOS: Foram utilizados os materiais Luci Sof® (Dentsply), Molloplast-B® (Dentax) e Sofreliner® (Tokuyama), e os agentes de limpeza Hipoclorito de Sódio a 0,5% (Medicinallis-Farmácia de Manipulação) e Efferdent® (Warner-Lamber). Foram confeccionadas 20 amostras de cada material, com dimensões de 25X14X3mm. Foram realizados 2 tratamentos: 1) Hipoclorito de Sódio a 0,5% a 37 + 1ºC, durante 20 minutos; 2) Peróxido Alcalino, a 37 + 1ºC, durante 30 minutos. Após as imersões, as amostras foram lavadas e imersas em água destilada, a 37 &plusmn; 1ºC, pelo período restante das 24 h. Esse processo foi repetido 8 vezes por dia, durante 90 dias. A dureza foi avaliada antes e após 360 e 720 ciclos, correspondente a 1 e 2 anos de uso clínico, respectivamente. O ensaio de dureza Shore A foi realizado em durômetro modelo GS-709 (Teclock-Japão), com aplicação de carga de 10 N por 1 segundo. Alterações macroscópicas, como perda de cor e alteração da superfície, foram avaliadas por um observador. Os resultados obtidos foram submetidos à ANOVA com medidas repetidas e ao Teste de Tukey (5%). RESULTADOS: Os materiais apresentaram diferença significante nos valores médios de dureza, independente do tratamento e do tempo. Luci Sof® e Sofreliner® aumentaram os valores médios de dureza inicialmente, os quais diminuíram após 720 ciclos significativamente, para ambos os tratamentos. Molloplast-B® não apresentou diferença significante nos diferentes tempos e tratamentos. CONCLUSÕES: Os tratamentos em agentes de limpeza não alteraram os valores de dureza dos reembasadores resilientes após 2 anos de simulação clínica. Sofreliner® apresentou os menores valores de dureza, em todos os tempos e tratamentos, apresentando-se como o material mais macio