Aspectos sociales, sobrecarga y calidad de vida de las madres de niños con microcefalia / Social aspects, work overload, and quality of life among mothers of children with microcephaly / Aspectos sociais, sobrecarga e qualidade de vida de mães de crianças com microcefalia

RESUMEN Introducción: Cuidar completamente de niños con microcefalia es un gran desafío para sus cuidadores. La situación de vulnerabilidad social junto con la complejidad de la atención puede llevar a sobrecarga con pérdida de la calidad de vida. Objetivo: Analizar la relación entre aspectos socioeconómicos, dominio social de la calidad de vida y la sobrecarga de madres cuidadoras de niños con microcefalia. Metodología: Estudio transversal con 105 participantes, mediante aplicación de cuestionarios sociodemográficos, WHOQOL-BREF, sobrecarga del cuidador. Se utilizaron pruebas ANOVA, t de Student, coeficiente de correlación de Pearson (r). Resultados: Población de madres mestizas (65.7%), desempleadas (88.6%), dependientes de la prestación social (76.2%), bajo nivel educativo (50.5%) e insuficiencia financiera (90.5%). El promedio del dominio social se consideró bajo (51.11). Hubo asociación entre beneficio social y puntaje de calidad de vida total (p=0.046). Las madres sufren sobrecarga severa (39%) e intensa (30.4%). Se encontró asociación entre niveles de sobrecarga y variables etnia (p= 0.027), ocupación (p= 0.043) y medios de transporte (p <0.0001). La sobrecarga tiene impacto negativo en la calidad de vida (r= -.463, p <0.0001), percepción de la calidad de vida (r= -.476, p= <0.0001), calidad de vida total (r= -.576, p= <0.0010). Conclusiones: Las madres cuidadoras manifiestan sobrecarga con pérdida de calidad de vida. Los aspectos sociales influyen directamente y pueden potenciar la sobrecarga del cuidado. El personal de enfermería tiene un papel fundamental para crear e implementar líneas de atención con énfasis en promover la salud y alivio de la sobrecarga en el cuidador.

ABSTRACT Introduction: Taking care of children with microcephaly is a great challenge for their care providers because of the associated social vulnerability, work overload, and loss of quality of life. Objective: To analyze the associations related to the social aspects, the quality of life, and the work overload among care providing mothers of children with microcephaly. Methodology: This is a transversal study with 105 participants. Social and demographic questionnaires and WHOQOL-BREF were used. ANOVA tests, Student's t-test, and Pearson's correlation coefficient were calculated. Results: 65.7% were of mixed ethnicity; 88.6% were unemployed; 76.2% were dependent on Social Welfare; 50.5% had a low level of education; and 90.5% were financially insufficient. The social domain average was considered low (51.11). An association was found between social benefits and quality of life (p=0.046). 39% of these mothers suffer from severe work overload while 30.4% suffer from intense work overload. An association was found between the levels of work overload and ethnicity (p= 0.027), occupation (p= 0.043), and transportation means (p <0.0001). Work overload had a negative impact on the quality of life (r= -.463, p <0.0001), the perception of quality of life (r= -.476, p= <0.0001), and total quality of life (r= -.576, p= <0.0010). Conclusions: These care providing mothers suffer work overload with an associated loss of quality of life. Social aspects have a direct influence and can increase work overload. Nursing professionals have a fundamental role in the creation and implementation of attention initiatives aimed at promoting health and relief to this kind of care providing mothers.

RESUMO Introdução: Cuidar completamente das crianças com microcefalia é um grande desafio para os seus cuidadores. A situação de vulnerabilidade social aliada à complexidade do cuidado pode levar à sobrecarga com perda de qualidade de vida. Objetivo: Analisar a relação entre aspectos socioeconómicos, domínio social da qualidade de vida e sobrecarga de mães cuidadoras de crianças com microcefalia. Metodologia: Estudo transversal com 105 participantes, por meio da aplicação de questionários sociodemográficos, WHOQOL-BREF, sobrecarga do cuidador. Foram utilizados os testes ANOVA, t de Student, e coeficiente de correlação de Pearson (r). Resultados: População de mães pardas (65.7%), desempregadas (88.6%), dependentes de benefícios sociais (76.2%), baixa escolaridade (50.5%) e insuficiência financeira (90.5%). A média do domínio social foi considerada baixa (51.11). Houve associação entre benefício social e pontuação total de qualidade de vida (p=0.046). As mães sofrem sobrecarga severa (39%) e intensa (30.4%). Foi encontrada associação entre os níveis de sobrecarga e as variáveis de etnia (p= 0.027), ocupação (p= 0.043) e meio de transporte (p <0.0001). A sobrecarga tem um impacto negativo na qualidade de vida (r= -.463, p <0.0001), percepção de qualidade de vida (r= -.476, p= <0.0001), qualidade de vida total (r= -.576, p= <0.0010). Conclusões: As mães cuidadoras sofrem sobrecarga com perda de qualidade de vida. Os aspectos sociais influenciam diretamente e podem potenciar a sobrecarga do cuidado. A enfermagem tem um papel fundamental na criação e implementação de linhas de cuidados com ênfase na promoção da saúde e no alívio da sobrecarga do cuidador.

Maternal polymorphisms in the FADS1 and FADS2 genes modify the association between PUFA ingestion and plasma concentrations of omega-3 polyunsaturated fatty acids.

There is a lack of studies about polymorphisms in FADS genes in pregnant women. We aimed to verify the interaction between three FADS gene polymorphisms (rs174561; rs174575; rs3834458) and dietary α-linolenic acid (ALA) or linoleic/α-linolenic acid ratio (LA/ALA) and plasma concentrations of omega-3 (n-3) PUFAs in pregnant women. Of the 250 women evaluated, the homozygous for the rs174561 and rs3834458 minor allele had high plasma ALA concentrations at the highest ALA and LA/ALA ratio tertile (p < 0.05). Plasma concentrations of EPA and DHA were not influenced by diet. For the rs174575 SNP, pregnant women who carried the minor allele presented lower proportions of plasma EPA in the second LA/ALA ratio tertile (p < 0.05). Increased dietary intake of ALA and LA/ALA ratio promoted plasma ALA accumulation in homozygotes for the minor allele rs174561 and rs3834458. Moderate intake of LA/ALA ratio may reduce plasma concentration of EPA in pregnants carrying the rs174575 minor allele.

Ureaplasma urealyticum and U. parvum in sexually active women attending public health clinics in Brazil.

Ureaplasma urealyticum and U. parvum have been associated with genital infections. The purpose of this study was to detect the presence of ureaplasmas and other sexually transmitted infections in sexually active women from Brazil and relate these data to demographic and sexual health, and cytokines IL-6 and IL-1ß. Samples of cervical swab of 302 women were examined at the Family Health Units in Vitória da Conquista. The frequency of detection by conventional PCR was 76·2% for Mollicutes. In qPCR, the frequency found was 16·6% for U. urealyticum and 60·6% U. parvum and the bacterial load of these microorganisms was not significantly associated with signs and symptoms of genital infection. The frequency found for Trichomonas vaginalis, Neisseria gonorrhoeae, Gardnerella vaginalis and Chlamydia trachomatis was 3·0%, 21·5%, 42·4% and 1·7%, respectively. Higher levels of IL-1ß were associated with control women colonized by U. urealyticum and U. parvum. Increased levels of IL-6 were associated with women who exhibited U. parvum. Sexually active women, with more than one sexual partner in the last 3 months, living in a rural area were associated with increased odds of certain U. parvum serovar infection.

Changes in energetic metabolism of Biomphalaria glabrata (Mollusca, Planorbidae) in response to exogenous calcium / Alterações no metabolismo energético de Biomphalaria glabrata em resposta ao cálcio exógeno

Abstract Calcium is considered an essential element for the metabolism of aquatic snail Biomphalaria glabrata (Say, 1818), intermediate host of Schistosoma mansoni Sambon, 1907 in Brazil, and represents a limiting factor to its distribution and adaptation to the environment. This study investigated the effect of different concentrations of exogenous CaCO3 on the energetic metabolism of B. glabrata for better understanding the physiological interference of chemical elements dissolved in the environment with the physiology of this species. Sixty-day-old snails were distributed into six groups, five exposed to different concentrations of CaCO3 (20, 40, 60, 80 and 100 mg/L) and a control group. The exposure to CaCO3 was assessed over time, with analysis of 15 snails of each group in the following intervals: 1, 14, 21 or 30 days for hemolymph extraction. Concentrations of calcium and glucose in the hemolymph were determined by commercial kits, and organic acids were extracted using an ion exchange column and analyzed by high-performance liquid chromatography. Concentration of calcium in the hemolymph showed no significant difference (p>0.05) from the control group and between the concentrations tested. Concentration of glucose decreased (p<0.05) in the treatments of exposure to 20 and 40 mg/L and increased when exposed to 80 and 100 mg/L CaCO3 compared to control and to other concentrations tested over 30 days. The organic acids pyruvate, oxaloacetate, citrate, succinate, fumarate, beta-hydroxybutyrate and lactate presented increased concentrations, while propionate and acetoacetate, decreased concentrations, when exposed to CaCO3 compared to control. Considering the influence of different periods of exposure to CaCO3, on the 14th day, there were stronger alterations in the metabolism of B. glabrata. In conclusion, exposure to CaCO3 reduced the concentration of glucose, which is metabolized into pyruvate, the final product of glycolysis, and also influenced the energetic metabolism pathways, indicating an aerobic or partially anaerobic functioning.

Resumo O cálcio é considerado um elemento essencial no metabolismo do molusco aquático Biomphalaria glabrata (Say, 1818), principal hospedeiro intermediário de Schistosoma mansoni Sambon, 1907 no Brasil e, tem sido descrito como um fator limitante na distribuição e adaptação desse molusco no ambiente. O presente trabalho avaliou o efeito de diferentes concentrações de carbonato de cálcio (CaCO3) exógeno ao metabolismo energético de B. glabrata, a fim de subsidiar uma melhor compreensão da interferência de elementos químicos dissolvidos no meio aquático na fisiologia destes moluscos. Foram utilizados moluscos com sessenta dias de vida, distribuídos em seis grupos, cinco expostos a diferentes concentrações de CaCO3 (20, 40, 60, 80 e 100mg/L) e um controle. A exposição ao CaCO3 foi avaliada em função do tempo, sendo retirados 15 moluscos de cada grupo nos seguintes intervalos: 1, 14, 21 ou 30 dias para extração da hemolinfa. As concentrações de cálcio e glicose na hemolinfa foram determinadas usando-se kits comercial e os ácidos orgânicos foram extraídos por meio da coluna de troca iônica e analisados através cromatografia líquida de alta eficiência. Os resultados demonstraram que a concentração de cálcio na hemolinfa não apresentou diferença significativa (p>0,05) em relação ao controle e nas concentrações testadas. A concentração de glicose diminuiu (p<0,05) nas exposições a 20 mg e 40 mg/L e aumentou nas exposições a 80 mg e 100 mg/L de CaCO3 em relação ao controle e demais concentrações testadas ao longo de 30 dias. Os ácidos orgânicos piruvato, oxaloaceato, citrato, succinato, fumarato, β-hidroxibutirato e lactato tiveram suas concentrações aumentadas, enqunato, propionato e acetoacetato tiveram suas concentrações diminuídas na exposição ao CaCO3 comparada ao controle. Quanto a influência dos diferentes períodos de exposição ao CaCO3, aos 14 dias, as alterações no metabolismo de B. glabrata foram mais expressivas. Conclui-se que as exposições ao CaCO3 influenciaram na redução de glicose, sendo esta metabolizada a piruvato, produto final da glicólise e alteraram as vias de metabolismo energético, indicando um funcionamento aeróbio ou parcialmente anaeróbio.

The uremic toxin methylguanidine increases the oxidative metabolism and accelerates the apoptosis of canine neutrophils.

We investigated the hypothesis that the increased concentration of plasma methylguanidine (MG) increases oxidative metabolism and accelerates apoptosis of neutrophils from dogs with chronic kidney disease (CKD). To achieve this, the levels of MG were quantified in healthy (n=16) and uremic dogs with CKD stage 4 of according to the guidelines of the International Renal Interest Society (IRIS, 2015) (n=16) using high performance liquid chromatography (HPLC). To evaluate the isolated effect of MG on neutrophil oxidative metabolism and apoptosis, neutrophils isolated from 12 healthy dogs were incubated with the highest concentration of plasma MG (0.005g/L) observed in dogs with CKD. Neutrophil oxidative metabolism was assessed by flow cytometry, using the probes hydroethidine for superoxide production and 2',7'-dichlorofluorescein diacetate for hydrogen peroxide production, with or without phorbol myristate acetate (PMA) stimulus. Neutrophil apoptosis and viability were also evaluated in flow cytometer using the Annexin V-PE system, with or without the apoptosis-inducing effect of camptothecin. Uremic dogs presented higher concentrations of MG (p<0.0001), increased oxidative stress and primed neutrophils with higher apoptosis rate. The neutrophil abnormalities observed in vivo were also reproduced in vitro, using cells isolated from healthy dogs and incubated with MG. We obtained strong evidence that in dogs with CKD, increased MG levels contributed to oxidative stress and potentially compromised the non-specific immune response by altering the oxidative metabolism and viability of canine neutrophils.

Changes in energetic metabolism of Biomphalaria glabrata (Mollusca, Planorbidae) in response to exogenous calcium.

Calcium is considered an essential element for the metabolism of aquatic snail Biomphalaria glabrata (Say, 1818), intermediate host of Schistosoma mansoni Sambon, 1907 in Brazil, and represents a limiting factor to its distribution and adaptation to the environment. This study investigated the effect of different concentrations of exogenous CaCO3 on the energetic metabolism of B. glabrata for better understanding the physiological interference of chemical elements dissolved in the environment with the physiology of this species. Sixty-day-old snails were distributed into six groups, five exposed to different concentrations of CaCO3 (20, 40, 60, 80 and 100 mg/L) and a control group. The exposure to CaCO3 was assessed over time, with analysis of 15 snails of each group in the following intervals: 1, 14, 21 or 30 days for hemolymph extraction. Concentrations of calcium and glucose in the hemolymph were determined by commercial kits, and organic acids were extracted using an ion exchange column and analyzed by high-performance liquid chromatography. Concentration of calcium in the hemolymph showed no significant difference (p>0.05) from the control group and between the concentrations tested. Concentration of glucose decreased (p<0.05) in the treatments of exposure to 20 and 40 mg/L and increased when exposed to 80 and 100 mg/L CaCO3 compared to control and to other concentrations tested over 30 days. The organic acids pyruvate, oxaloacetate, citrate, succinate, fumarate, beta-hydroxybutyrate and lactate presented increased concentrations, while propionate and acetoacetate, decreased concentrations, when exposed to CaCO3 compared to control. Considering the influence of different periods of exposure to CaCO3, on the 14th day, there were stronger alterations in the metabolism of B. glabrata. In conclusion, exposure to CaCO3 reduced the concentration of glucose, which is metabolized into pyruvate, the final product of glycolysis, and also influenced the energetic metabolism pathways, indicating an aerobic or partially anaerobic functioning.

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer.

Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations. Understanding how these mutations impact on ER function is a prerequisite for identifying methods to treat breast cancer patients featuring such mutations. Towards this end, we used CRISPR-Cas9 genome editing to make a single allele knock-in of the most commonly mutated amino acid residue, tyrosine 537, in the estrogen-responsive MCF7 breast cancer cell line. Genomic analyses using RNA-seq and ER ChIP-seq demonstrated that the Y537S mutation promotes constitutive ER activity globally, resulting in estrogen-independent growth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen and fulvestrant. Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. These studies confirm the functional importance of ER mutations in endocrine resistance, demonstrate the utility of knock-in mutational models for investigating alternative therapeutic approaches and highlight CDK7 inhibition as a potential therapy for endocrine-resistant breast cancer mediated by ER mutations.

Obesity and vitamin D deficiency: a systematic review and meta-analysis.

Over the past decade, there have been an increasing number of studies on the association between vitamin D deficiency and anthropometric state. However, we did not identify any meta-analyses of the relationship between obesity and vitamin D deficiency in different age groups. Thus, we evaluated the association between obesity and vitamin D deficiency. We searched for observational studies published up to April 2014 in PubMed/Medline, Web of Science and Scopus databases. We performed a meta-analysis in accordance with the random-effects model to obtain the summary measurement (prevalence ratio, PR). Among the 29,882 articles identified, 23 met the inclusion criteria. The prevalence of vitamin D deficiency was 35% higher in obese subjects compared to the eutrophic group (PR: 1.35; 95% CI: 1.21-1.50) and 24% higher than in the overweight group (PR: 1.24; 95% CI: 1.14-1.34). These results indicate that the prevalence of vitamin D deficiency was more elevated in obese subjects. The vitamin D deficiency was associated with obesity irrespective of age, latitude, cut-offs to define vitamin D deficiency and the Human Development Index of the study location.

Probucol mitigates streptozotocin-induced cognitive and biochemical changes in mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss and cognitive impairments. Although AD is the most prevalent aging-related neurodegenerative disease, therapeutic strategies remain palliative. Recent studies have shown that probucol presents neuroprotective effects in experimental models of neurodegenerative disease. The present study aimed to investigate the potential protective effects of probucol against streptozotocin (STZ)-induced cognitive impairment and hippocampal biochemical changes (oxidative stress-related parameters, acetylcholinesterase (AChE) activity, cholesterol levels and ß-secretase (BACE) protein levels) in mice. Adult Swiss mice received STZ [150 µg/bilateral, i.c.v.], and treated daily with probucol (≅10 mg/kg/day, in drinking water, for 5 weeks,). Twenty-one days after i.c.v. administrations, STZ-infused animals displayed significant deficits in cognition (evaluated in the displaced and new object recognition tasks), which were paralleled by a significant increase in hippocampal AChE activity. Moreover, STZ-infused mice showed increased levels of BACE and decreased glutathione reductase (GR) activity in the hippocampus compared with the control group. Probucol treatment significantly protected against the behavioral and hippocampal biochemical changes induced by STZ. However, it was unable to prevent STZ-induced increase of hippocampal BACE levels and did not change hippocampal cholesterol levels. It is noteworthy that probucol treatment increased the glutathione peroxidase (GPx) activity per se independent of STZ injection. The present findings are the first to show that i.c.v. STZ infusions are able to increase hippocampal BACE expression. Moreover, the results also show that probucol can counteract STZ-induced cognitive impairments and biochemical parameters independently of potential modulator effects toward BACE levels. The study is the first to report the protective effects of probucol against STZ-induced biochemical hippocampal changes and behavioral impairments, rendering this compound a promising molecule for further pharmacological studies on the search for therapeutic strategies to treat or prevent AD.

Hypercholesterolemia as a risk factor for depressive disorder?

AIMS: Epidemiological findings demonstrated that increased plasma cholesterol levels are frequently observed in depressive patients. In this regard, there is enhancing evidence that hypercholesterolemia is associated with impairment of brain function. Recently, we demonstrated that low-density lipoprotein receptor knockout (LDLr(-/-)) mice- a widely used rodent model of familial hypercholesterolemia - exhibited memory deficits and cortico-cerebral mitochondrial dysfunction. In this study, we aimed to assess the hypercholesterolemic mice in predictive tasks for depressive-like behavior. METHODS: Adult wild type C57BL/6 and LDLr (-/-) mice were evaluated in two tests for depressive like behavior, the splash test and forced swimming test. In addition, the activity of monoamine oxidase isoforms and the mRNA levels of hemeoxygenase-1 were assessed in the hippocampus and cerebral cortex of C57BL/6 and LDLr (-/-) mice. Finally, the blood-brain-barrier (BBB) permeability was investigated using the AQP-4 immunofluorescence staining in the mice hippocampus. RESULTS: The LDLr (-/-) mice showed a significant reduction in the grooming time in the splash test and increased immobility time in the forced swimming test, and both parameters were reversed by fluoxetine antidepressant treatment (10mg/kg, 7 days, o.g.). Interestingly, the depressive like behavior of LDLr (-/-) mice was associated with increased activity of monoamine oxidase A, decreased hemeoxygenase-1 mRNA levels and increase of BBB permeability in the hippocampus. CONCLUSIONS: Overall, these data provide new evidence that hypercholesterolemia could trigger brain alterations involved in depressive disorders.

Qualidade do leite de propriedades familiares praticantes de integração lavoura-pecuária em função do uso do solo / Milk quality of family farms practicing crop-livestock integration depending on land use

O objetivo do estudo foi investigar o uso do solo em propriedades familiares (PF) manejadas sob integração lavoura-pecuária (ILP) em bacia hidrográfica e relacionar com a qualidade do leite. Para tal, 14 PF foram caracterizadas e agrupadas quanto ao uso do solo (Grupos 1, 2 e 3) e monitoradas quanto à qualidade do leite, durante os meses de maio de 2010 a fevereiro de 2011. Nas amostras de leite, avaliou-se o teor de gordura, proteína e sólidos não gordurosos. Observou-se que o uso do solo objetivando o cultivo de grãos em detrimento do pastejo animal influencia negativamente o teor de gordura e proteína, em média 6,3% e 5,4%, respectivamente, sobretudo no período de verão. Assim, o planejamento de uso do solo em PF manejadas sob ILP é fundamental, pois a competição entre as atividades reflete na qualidade do leite. As PF especializadas na atividade leiteira apresentam melhor qualidade do leite durante as estações do ano.

The aim of this study was to investigate the land use practiced on family farms (FF), managed under crop-livestock integration (CLP) in the watershed and to evaluate the quality of milk. 14 FFs were characterized and grouped regarding soil use (Group 1, 2 and 3) and the quality of milk was monitored during the months of May, 2010 to February 2011. In these milk samples, we evaluated the fat, protein and non-fat solids content. It can be observed that the use of soil in a crop-livestock integration system, when the grain cultivation is prioritized over the animal grazing, influences negatively the fat and protein content, on average 6.3% and 5.4%, respectively, especially during the summer. Thus, the planning of the use of soil in FF managed under CLP is essential, because the competition between the activities was reflected in the quality of milk. The FF specialized in dairy farming produces better quality milk in all annual seasons.

Association of polymorphism +874 A/T of interferon-γ and susceptibility to the development of tuberculosis: meta-analysis.

The immune defence against Mycobacterium tuberculosis is complex and involves multiple interacting cells. Studies in subjects with polymorphisms in genes for IFN or its receptor gene evaluate their relationship with mycobacterium infections. The purpose of this study was to analyze the evidence of the effect of polymorphism +874 A/T from interferon-γ on the occurrence of tuberculosis. We performed a meta-analysis of studies published between June 2002 and April 2012. The articles analyzed assessed the relationship between the polymorphism +874 A/T and the development of tuberculosis. The meta-analysis was performed with a random effect model, considering the heterogeneity among studies. Genotype TT showed a protective effect (OR, 0.77; 95% CI = 0.67-0.88) while genotype AA may be associated with increased susceptibility to developing tuberculosis (OR, 1.51; 95% CI = 1.38-1.65). In relation to alleles, we can verify that the A allele is related to the development of tuberculosis (OR, 1.56; 95% CI = 1.42-1.71). This information reinforces the importance of host genetics in the development of infectious diseases. Studies in this area can result in the promotion of new and more accurate genetic markers.

Genotoxicity of organoselenium compounds in human leukocytes in vitro.

DNA damage and cell viability of human leukocytes cells were examined as simple tests for screening the potential toxicity of organoselenium compounds. Leukocytes were incubated with different organoselenium compounds at 4, 10, 40 and 100 microM or vehicle (DMSO) for 3h at 37 degrees C before of in vitro assays. Cell viability was determined by Trypan blue exclusion. DNA damage was assessed using the alkaline comet assay with silver staining. The exposure of leukocytes to (S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl, (S)-2-amino-1-diselenide-3-phenylpropanyl, 3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide, in the range of 10-100muM, induced a significant increase in Damage Index (DI). The genotoxic effect of all compounds was associated with high frequencies of cells with damage level 4 and all compounds caused a decrease in cell viability. Our results suggest that the selenium compounds tested were genotoxic and cytotoxic to human leukocytes cells in vitro and that the organoselenium amino acid derivatives ((S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl and (S)-2-amino-1-diselenide-3-phenylpropanyl) were more genotoxic than aromatic derivatives (3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide). These effects may be linked to the pro-oxidant activity exhibited by selenium compounds when used in relatively high concentrations.

Hemolytic and genotoxic evaluation of organochalcogens in human blood cells in vitro.

This study investigated the hemolytic and genotoxic effect of different organoselenium and organotellurium compounds in human blood cells, as simple tests for screening the toxicity of organochalcogenides. For osmotic fragility (OF) test, samples of total blood were incubated with the organochalcogens at 4, 8, 50, 75 and 100 microM or vehicle (DMSO) for 90 min at 37 degrees C. The EC(50) values for hemolysis were significantly increased in erythrocytes exposed to diphenyl selenide (II), diphenyl diselenide (III), diphenyl telluride (IV), diphenyl ditelluride (V), (S)-2-amino-1-diselenide-3-methylpropanyl (IX), butyl(styryl)telluride (XIII) and 2-(butyltellurium)furan (XIV) at higher concentrations tested. The exposure of erythrocytes to organochalcogens diphenyl diselenide (II) and butyl(styryl)telluride (XIII), which had greater hemolytic effect, did not modify catalase activity, reactive oxygen species (ROS) production and -SH content. On the other hand, Na(+)/K(+) ATPase activity of erythrocyte ghosts was significantly inhibited by the compounds diphenyl diselenide (II) and butyl(styryl)telluride (XIII) (P<0.05) in a concentration-dependent manner. The inhibition of Na(+)/K(+) ATPase activity was completely reversed by dithiothreitol (DTT); indicating reaction of these organochalcogens with thiol groups of the enzyme. The thiol oxidase activity of the compounds II and XIII was supported by the fact that the rate of DTT oxidation was increased significantly by both chalcogens. In the higher concentrations, the compounds (II) and (XIII) were strongly genotoxic and cytotoxic to human leukocytes cells, as verified by the DNA damage and cell viability evaluation. Our results suggest that at relatively high concentration organochalcogenides exhibit hemolytic and genotoxic action in human blood cells, which are probably linked to their thiol oxidase activity and preferential interaction with sulfhydryl groups critical to enzymes.

Absence of antimutagenicity of Cochlospermum regium (Mart. and Schr.) Pilger 1924 by micronucleus test in mice.

Cochlospermum regium (Mart. and Schr.) Pilger, popularly known as "algodãozinho do campo", is a medicinal plant that grows in the Cerrado of Brazil. This plant has been used in traditional medicine against various diseases such as leucorrhoea, gastritis and ulcers. It has also been effective in treating skin problems like pimples, boils and blotches. In the present study, the in vivo antimutagenicity of aqueous extract of C. regium was evaluated. The Micronucleus Test was performed in polychromatic erythrocytes from Swiss male mice treated with one of the four doses of extract of the plant (19, 38, 76 and 114 mg.kg(-1) body weight), administered by intraperitonial injection (i.p.) simultaneously with cyclophosphamide (24 mg.kg(-1) b.w.) or mitomycin C (4 mg.kg(-1) b.w.). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed no significant reduction of the micronucleated polychromatic erythrocytes frequency (P > 0.05). In conclusion, the data indicate that C. regium roots aqueous extract, for the conditions used, did not exhibit the antimutagenic effect.

Absence of antimutagenicity of Cochlospermum regium (Mart. and Schr.) Pilger 1924 by micronucleus test in mice

Cochlospermum regium (Mart. and Schr.) Pilger, popularly known as "algodãozinho do campo", is a medicinal plant that grows in the Cerrado of Brazil. This plant has been used in traditional medicine against various diseases such as leucorrhoea, gastritis and ulcers. It has also been effective in treating skin problems like pimples, boils and blotches. In the present study, the in vivo antimutagenicity of aqueous extract of C. regium was evaluated. The Micronucleus Test was performed in polychromatic erythrocytes from Swiss male mice treated with one of the four doses of extract of the plant (19, 38, 76 and 114 mg.kg-1 body weight), administered by intraperitonial injection (i.p.) simultaneously with cyclophosphamide (24 mg.kg-1 b.w.) or mitomycin C (4 mg.kg-1 b.w.). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed no significant reduction of the micronucleated polychromatic erythrocytes frequency (P > 0.05). In conclusion, the data indicate that C. regium roots aqueous extract, for the conditions used, did not exhibit the antimutagenic effect.

Cochlospermum regium (Mart. & Schr.) Pilger, conhecido popularmente como "algodãozinho-do-campo", é uma planta medicinal que cresce no Cerrado brasileiro. Esta planta tem sido utilizada na medicina tradicional contra várias doenças como leucorréia, gastrites e úlceras. Esta também tem se mostrado efetiva no tratamento de doenças de pele como espinhas, furúnculos e manchas. No presente estudo, foi avaliada a antimutagenicidade do extrato aquoso de C. regium pelo Teste do Micronúcleo in vivo. Este ensaio foi realizado em eritrócitos policromáticos de camundongos machos Swiss tratados com quatro concentrações diferentes do extrato da planta (19, 38, 76 e 114 mg.kg-1 por peso corpóreo), administrado por injeção intraperitonial (i.p.) simultaneamente com ciclofosfamida (24 mg.kg-1 p.c.) ou mitomicina C (4 mg.kg-1 p.c.). A citotoxicidade foi avaliada pela razão eritrócitos policromáticos e normocromáticos (PCE/NCE). Os resultados obtidos não mostraram redução significativa da freqüência de eritrócitos policromáticos micronucleados (P > 0,05). Em conclusão, os resultados indicam que o extrato aquoso de raiz de C. regium, para as condições utilizadas, não exibiu efeito antimutagênico.

Folate, vitamin B12 and total homocysteine levels in neonates from Brazil.

OBJECTIVE: To determine folates, vitamin B12 and total homocysteine levels among neonates from mothers of low or high socioeconomic status. DESIGN: We carried out a cross-sectional transversal study comprising 143 neonates from two maternity hospitals in the city of Salvador, Northeast of Brazil. Cord blood samples were obtained at the time of delivery from newborns from low (group 1, n=77) or high (group 2, n=66) socioeconomic status. The vitamin B12 and folates were analyzed by electrochemiluminescence immunoassay and by a competitive test using a natural folate-binding protein (FBP), respectively. Total homocyteine levels were measured by fluorescence polarization immunoassay. Maternal environmental risk factors for pregnancy complications were obtained from all mothers. RESULTS: Only 2% of women from group 1 received prenatal care/vitamin supplementation, whereas almost all mothers from group 2 (96%) were properly followed. Anemia and/or infections pre- or during pregnancy was more prevalent among mothers of babies from group 1. Folate levels among newborns from group 1 and 2 were 7.38+/-2.71 and 8.83+/-4.06 ng/ml, respectively. No difference in the vitamin B12 levels was determined between groups. In addition, tHcy serum levels were higher among newborns from group 1 compared to those from group 2 (8.54+/-4.06 vs 6.35+/-1.33 micromol/l, respectively; P=0.005). CONCLUSION: These results demonstrate that unprivileged young woman has limited accesses to prenatal care, present high-risk factors that hamper both maternal and newborn health. Maternal and newborn health status could be improved by simply reinforcing the use of folate-enriched diet. The work presented illustrates the challenges that developing countries have to face in order to provide preventive adequate health care to the population at large.

A new depsipeptide from the sacoglossan mollusk Elysia ornata and the green alga Bryopsis species.

A new cyclic depsipeptide, kahalalide O (1), was isolated from the sacoglossan Elysia ornata and its algal diet Bryopsis sp. The structure was elucidated primarily by NMR and MS spectral methods, and the stereochemistry of the amino acid residues was determined by chiral HPLC and Marfey analyses. Unlike the related metabolite kahalalide F, which is in development as a potential anticancer agent, kahalalide O (1) was inactive in arresting the growth of P-388, A549, HT29, and MEL28 cancer cell lines in vitro.