Genotoxic and mutagenic properties of Bauhinia platypetala extract,a traditional Brazilian medicinal plant

Ethnopharmacological relevance

Bauhinia platypetala Burch. is a traditionally used Brazilian medicinal plant, although no evidence in the literature substantiates the safety of its use.

Aim of the study

The aim of this study was to investigate the safety of the ethanolic extract and the ethereal fraction of B. platypetala leaves.

Materials and methods

The identification of chemical compounds from the B. platypetala ethanolic extract and its ethereal fraction was performed by GC/MS and ESI-MS/MS. The plant’s toxicological, cytotoxic, mutagenic and genotoxic properties were determined in Saccharomyces cerevisiae strains and V79 cell culture by survival assays and comet assay.

Results

The major compound identified in the B. platypetala ethanolic extract is palmitic acid, kaempferitirin and quercitrin, while the B. platypetala ethereal fraction was found to be rich in phytol, gamma-sitosterol and vitamin E. Moreover, the results indicated that the B. platypetala ethanolic extract has an anti-oxidative effect against H₂O₂ in yeast. In addition, the B. platypetala ethanolic extract did not induce mutagenic effects on the S. cerevisiae N123 strain, but the ethereal fraction of B. platypetala at higher concentrations (250–500 μg/mL) induced cytotoxicity and mutagenicity. A slight cytotoxic effect was observed in mammalian V79 cells; however, both the B. platypetala ethanolic extract and its ethereal fraction were able to induce DNA strand breaks in V79 cells, as detected by the alkaline comet assay.

Conclusion

The B. platypetala ethanolic extract has antioxidant action and showed absence of mutagenic effects in yeast S. cerevisiae. On the other hand B. platypetala ethereal fraction is mutagenic and does not show antioxidant activity in yeast. In mammalian cells B. platypetala ethanolic extract and it's ethereal fraction induce cyotoxic and genotoxic action.     

Susceptibility genetic variants associated with early-onset colorectal cancer

Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.     

DNA damage induced by the anthracycline cosmomycin D in DNA repair-deficient cells

Purpose

Anthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side effects related to cardiotoxicity. New anthracyclines have been designed and tested, but the first ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene.

Methods

We assessed the induction of apoptosis (Sub-G₁) by cosmomycin D in nucleotide excision repair-deficient fibroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay).

Results

Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with highest apoptosis levels observed 96 h after treatment. The effects of cosmomycin D were equivalent to those obtained with doxorubicin. The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells, and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay.

Conclusions

Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to differences in structure between cosmomycin D and doxorubicin.     

Intrauterine contraception in Saint Louis: a survey of obstetrician and gynecologists' knowledge and attitudes

Background

Many obstacles to intrauterine contraception (IUC) use exist, including provider and patient misinformation, high upfront cost and clinician practice patterns. The aim of our study was to investigate knowledge and attitudes about IUC among obstetricians and gynecologists in the area of Saint Louis.

Study Design

We mailed a self-administered, anonymous survey to 250 clinicians who provide obstetric and gynecologic care in Saint Louis City and County which included questions about demographics, training, family planning visits and intrauterine contraceptive knowledge and use.

Results

The overall survey response rate among eligible clinicians was 73.7%. Clinicians who had recently finished training or saw higher numbers of contraceptive patients per week were more likely to insert IUC than clinicians who completed training prior to 1989 or saw fewer contraceptive patients. Several misconceptions among clinicians were identified, including an association between intrauterine contraceptives and an elevated risk of pelvic inflammatory disease.

Conclusions

Physician misconceptions about the risks of IUC continue to occur. Improved clinician education is greatly needed to facilitate the use of these highly effective, long-acting, reversible methods of contraception.     

Observation as a therapeutic intervention for infants and young children in care

More than half of all children entering care in the UK are infants and children under five. The emotional and mental health needs of this population tend to be overlooked. Research described in this paper aimed to find out about the experience of an infant or young child in care and to inform training and support for health and social care professionals. The study found that therapeutic observation with a looked-after infant was feasible and provided an in-depth perspective on the experiences of the baby and his foster carers. The paper outlines the clinical context, defines therapeutic observation, describes stages in the first year of life of the observed infant and his transition to adoption, discusses functions of the therapeutic observer, describes applications of the research and makes suggestions for further research.     

Effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT—phantom study

Background

CT optimization has a special importance in children. Smaller body size accentuates the importance of patient positioning affecting both radiation dose and image quality.

Objective

To determine the effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT examination.

Materials and methods

Chest scans of a pediatric 5-year anthropomorphic phantom were performed in different vertical positions (?6 cm to +5.4 cm) with a 64-slice CT scanner. Organ doses were measured with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Image noise and contrast were determined from the CT number histograms corresponding to different tissues.

Results

Significant changes in organ doses resulting from vertical positioning were observed, especially in radiosensitive anterior organs. The breast dose increased up to 16% and the thyroid dose up to 24% in lower positions. The noise was increased up to 45% relative to the centre position in the highest and lowest vertical positions, with a particular increase observed on the anterior and posterior sides, respectively. Off-centering also affected measured image contrast.

Conclusion

Vertical off-centering markedly affects organ doses and measured image-quality parameters in pediatric chest CT examination. Special attention should be given to correct patient centering when preparing patients for CT scans, especially when imaging children.     

Prostaglandin inhibitors in preterm labour

Prematurity accounts for the majority of neonatal morbidity and mortality in the developed world. The process of labour resembles inflammation, with prostaglandin and cytokine production both before and during labour. Anti-inflammatory drugs therefore have the potential to prevent preterm delivery. Indomethacin is the only tocolytic drug proven to delay delivery beyond 37 weeks and to reduce the incidence of low birth weight (<2500 g). There are, however, fetal side-effects such as ductal constriction and impaired renal function associated with its use. It is the type 2 isoform of cyclo-oxygenase (COX-2), which is important for the production of prostaglandins within intrauterine tissues and that up-regulation of COX-2 is associated with labour. Although indomethacin is currently the most common non-steroidal anti-inflammatory drug (NSAID) used in the treatment of preterm labour, it was hoped that COX-2-selective drugs, used as tocolytics, would target COX-2 activity and potentially spare COX-1-specific fetal side-effects. Experience with sulindac and nimesulide has been linked with both constriction of the ductus arteriosus and oligohydramnios. It is unclear whether this is due to COX-2-dependent side-effects, or due to accumulation of drug in the fetal circulation leading to levels that would cause COX-1 inhibition. Currently, the use of COX-2-selective drugs should therefore be confined to randomized controlled trials.