Unjustified use of amber necklaces for teething symptoms alleviation: Succinic acid release underperforms compared with natural skin bacteria production.

BACKGROUND: There is limited evidence of succinic acid release from amber necklace that justifies its biological plausibility. AIM: This study aimed to evaluate the release of succinic acid from Baltic amber beads in the presence of Staphylococcus epidermidis. DESIGN: The Baltic amber beads from the necklace were stratified according to their weight (average 0.05 g ± 0.067). Subsequently, the beads (n = 8) were submerged in 0.9% buffered saline (Control) or brain-heart infusion culture medium in the presence of a commercial strain of S. epidermidis, a resident skin bacterium incubated at 37°C for 24 h or 7 days. The samples were centrifuged, and the supernatants were analyzed by 1H Nuclear Magnetic Resonance. Multivariate analyses were adopted using the sparse partial least squares discriminant analysis method (p < .05). RESULTS: The group incubated with saline solution showed small release of succinic acid only after 7 days. In the groups with S. epidermidis, the release of succinic acid was observed in the both presence and absence of amber beads, indicating that succinic acid is a product released by bacteria. CONCLUSIONS: It was found that amber beads do not exhibit the ability to release expressive succinic acid, especially in a short period of time, which does not justify their use in infants. The most production of succinic acid is tributed to S. epidermidis.

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway.

BACKGROUND: Ischemia-reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. METHODS: (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. RESULTS: (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. CONCLUSION: None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.

Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana) against gastrointestinal nematodes of goats / Atividade ovicida do ácido succínico isolado do resíduo de sisal (Agave sisalana) sobre nematoides gastrintestinais de caprinos

ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA) isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide) test. The SA induced a significant inhibition of egg hatching (P 0.05) at all concentrations tested (60 to 250µg mL-1), and the concentrations to inhibit 50% (EC50) and 90% (EC90) values (mean ± standard deviation) were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.(AU)

RESUMO: O objetivo deste estudo foi avaliar a atividade anti-helmíntica in vitro do ácido succínico (AS) isolado do resíduo de sisal sobre nematódeos gastrointestinais de caprinos, utilizando os ensaios de inibição da eclosão de ovos e motilidade larval. Além disso, a citotoxicidade do AS em culturas de células Vero foi investigada empregando-se o teste de MTT (brometo de 3-4,5-dimetiltiazol-2-ilo, brometo de 2,5-difeniltetrazólio). O AS promoveu redução significativa no percentual de eclosão de ovos (P 0,05) em todas as concentrações testadas (60 a 250g mL-1). As médias (± desvio padrão) da CE50 e CE90 (Concentração efetiva 50% e 90%) sobre ovos foram de 90.3±2.8 e 130±3.5g mL-1, respectivamente. O AS não apresentou atividade larvicida. O AS foi menos tóxico para as células Vero, com média do percentual de viabilidade celular igual a 85±6.2% na concentração de 130g mL-1. Os resultados sugerem que o AS tem potencial efeito anti-helmíntico, embora sejam necessários a realização de estudos in vivo para confirmar seu uso terapêutico.(AU)

Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana) against gastrointestinal nematodes of goats / Atividade ovicida do ácido succínico isolado do resíduo de sisal (Agave sisalana) sobre nematoides gastrintestinais de caprinos

ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA) isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide) test. The SA induced a significant inhibition of egg hatching (P 0.05) at all concentrations tested (60 to 250µg mL-1), and the concentrations to inhibit 50% (EC50) and 90% (EC90) values (mean ± standard deviation) were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.

RESUMO: O objetivo deste estudo foi avaliar a atividade anti-helmíntica in vitro do ácido succínico (AS) isolado do resíduo de sisal sobre nematódeos gastrointestinais de caprinos, utilizando os ensaios de inibição da eclosão de ovos e motilidade larval. Além disso, a citotoxicidade do AS em culturas de células Vero foi investigada empregando-se o teste de MTT (brometo de 3-4,5-dimetiltiazol-2-ilo, brometo de 2,5-difeniltetrazólio). O AS promoveu redução significativa no percentual de eclosão de ovos (P 0,05) em todas as concentrações testadas (60 a 250g mL-1). As médias (± desvio padrão) da CE50 e CE90 (Concentração efetiva 50% e 90%) sobre ovos foram de 90.3±2.8 e 130±3.5g mL-1, respectivamente. O AS não apresentou atividade larvicida. O AS foi menos tóxico para as células Vero, com média do percentual de viabilidade celular igual a 85±6.2% na concentração de 130g mL-1. Os resultados sugerem que o AS tem potencial efeito anti-helmíntico, embora sejam necessários a realização de estudos in vivo para confirmar seu uso terapêutico.

Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons.

Polycomb Repressive Complex 2 (PRC2) mediates transcriptional silencing by catalyzing histone H3 lysine 27 trimethylation (H3K27me3), but its role in the maturation of postmitotic mammalian neurons remains largely unknown. We report that the PRC2 paralogs Ezh1 and Ezh2 are differentially expressed during hippocampal development. We show that depletion of Ezh2 leads to increased expression of PSD-95, a critical plasticity gene, and that reduced PSD-95 gene transcription is correlated with enrichment of Ezh2 at the PSD-95 gene promoter; however, the H3K27me3 epigenetic mark is not present at the PSD-95 gene promoter, likely due to the antagonizing effects of the H3S28P and H3K27Ac marks and the activity of the H3K27 demethylases JMJD3 and UTX. In contrast, increased PSD-95 gene transcription is accompanied by the presence of Ezh1 and elongation-engaged RNA Polymerase II complexes at the PSD-95 gene promoter, while knock-down of Ezh1 reduces PSD-95 transcription. These results indicate that Ezh1 and Ezh2 have antagonistic roles in regulating PSD-95 transcription.

Diagnostic accuracy of renal pelvic dilatation for detecting surgically managed ureteropelvic junction obstruction.

PURPOSE: In this study we evaluate the diagnostic accuracy of renal pelvic dilatation for detecting infants with prenatal hydronephrosis who will need surgical intervention for ureteropelvic junction obstruction during followup. MATERIALS AND METHODS: Between 1999 and 2010, 371 newborns diagnosed with isolated prenatal hydronephrosis were prospectively followed. The main event of interest was the need for pyeloplasty. Diagnostic odds ratio, sensitivity, specificity and diagnostic accuracy (assessed by AUC) of fetal renal pelvic dilatation and postnatal renal pelvic dilatation were evaluated. RESULTS: A total of 312 patients were included in the analysis and 25 (7.5%) infants underwent pyeloplasty. The diagnostic performance for detecting the need for pyeloplasty was excellent for all ultrasonography measurements. The AUC was 0.96 (95% CI 0.92-0.98) for fetal renal pelvic dilatation, 0.97 (95% CI 0.95-0.98) for postnatal renal pelvic dilatation and 0.95 (95% CI 0.92-0.97) for the Society for Fetal Urology grading system. A cutoff of 18 mm for fetal renal pelvic dilatation and a cutoff of 16 mm for postnatal renal pelvic dilatation had the best diagnostic odds ratio to identify infants who needed pyeloplasty. Considering a diagnosis to be positive only if fetal renal pelvic dilatation was greater than 18 mm and postnatal dilatation was greater than 16 mm, sensitivity was 100% and specificity was 86% (95% CI 80.7-89.9). CONCLUSIONS: Our findings suggest that the combination of fetal and postnatal renal pelvic dilatation is able to increase the diagnostic accuracy for detecting infants who need a more comprehensive postnatal investigation for upper urinary tract obstruction.

Intoxicación familiar por mercurio elemental: caso clínico / Family poisoned by elemental mercury: a case report

Introduction: mercury is a heavy metal widely dispersed in nature, occurring in three chemical forms. Exposure to mercury at work sites and even at home may be clinically significant. Objective: to update the knowledge about the risks of this toxic element. Case report: the case of a teenager and his family poisoned by elemental mercury is reported. The diagnostic process was difficult, mainly due to an initial presumption of probable infectious etiology, unavailability of key anamnestic data and unusual clinical behavior, with signs and symptoms of multisystem compromise (neurological, hepatic, renal and dermatological compromise). Discussion: the study was based on literature review of various clinical presentations regarding this poisoning and its management, emphasizing the need for dimercaptosuccinic acid chelator. As a major public health problem, the importance of education and implementation of public policies to have a mercury-free environment is discussed.

Introducción: el mercurio es un metal pesado ampliamente distribuido en el medio ambiente, en sus tres formas químicas. La exposición a dicho metal en recintos laborales e incluso en el hogar, puede llegar a ser clínicamente significativa. Objetivo: actualizar el conocimiento acerca de los riesgos de este tóxico. Caso clínico: se presenta el caso clínico de un adolescente y su familia intoxicados por mercurio elemental, cuyo proceso diagnóstico fue difícil, principalmente por la presunción inicial de una probable etiología infecciosa, falta de disponibilidad de datos anamnésticos claves y el inusual comportamiento clínico, con signos y síntomas de compromiso multisistémico (neurológico, hepático, renal y dermatológico). Discusión: se revisa la literatura en relación a las diversas formas de presentación clínica de esta intoxicación y su manejo, destacando la utilidad del quelante ácido dimercaptosuccínico. Por ser un importante problema de salud pública, se destaca la trascendencia de la educación e implementación de políticas públicas por un ambiente libre de mercurio.

Produção de crisântemo (Dendranthema grandiflora Tzvelev.) ‘Snowdon’ em vaso II: ciclo da cultivar, comprimento, largura e área da folha

The aim of this study was to investigate the response of cultivation cycle, length, width and area leaf, to the growth retardant Daminozide, sprayed on the Chrysanthemum (Dendranthema grandiflora Tzvelev.) ‘Snowdon’ cultivated in pot. The study consisted of two experiments with five repetitions. The experiments were bifactorial 4 x 2, with four concentrations of Daminozide (0, 2.000, 4.000 and 6.000 mg.L-1) and two frequencies of application (weekly and bi-weekly) of product. Cultivation cycle, leaf length, width and area were determined. The ‘Snowdon’ was able to produce pots commercially acceptable, with increase in the cultivation cycle and decrease of the leaf size.

O objetivo do trabalho foi avaliar a resposta quanto ao ciclo e comprimento, largura e área da folha, ao redutor de crescimento Daminozide, pulverizado na cultivar de crisântemo (Dendranthema grandiflora Tzvelev.) de corte Snowdon, conduzida em vaso. O estudo foi composto por dois ensaios com cinco repetições, no delineamento experimental inteiramente casualizado bifatorial 4 x 2, sendo formado por quatro doses de Daminozide (0, 2000, 4000 e 6000 mg.L-1) e duas freqüências de aplicações (semanal e bissemanal). Os resultados mostraram que a cultivar Snowdon pode ser conduzida em vaso, porém, com aumento de ciclo e redução de até 28% na área da folha.

Produção de crisântemo (Dendranthema grandiflora Tzvelev.) ‘Snowdon em vaso II: ciclo da cultivar, comprimento, largura e área da folha

The aim of this study was to investigate the response of cultivation cycle, length, width and area leaf, to the growth retardant Daminozide, sprayed on the Chrysanthemum (Dendranthema grandiflora Tzvelev.) ‘Snowdon cultivated in pot. The study consisted of two experiments with five repetitions. The experiments were bifactorial 4 x 2, with four concentrations of Daminozide (0, 2.000, 4.000 and 6.000 mg.L-1) and two frequencies of application (weekly and bi-weekly) of product. Cultivation cycle, leaf length, width and area were determined. The ‘Snowdon was able to produce pots commercially acceptable, with increase in the cultivation cycle and decrease of the leaf size.

O objetivo do trabalho foi avaliar a resposta quanto ao ciclo e comprimento, largura e área da folha, ao redutor de crescimento Daminozide, pulverizado na cultivar de crisântemo (Dendranthema grandiflora Tzvelev.) de corte Snowdon, conduzida em vaso. O estudo foi composto por dois ensaios com cinco repetições, no delineamento experimental inteiramente casualizado bifatorial 4 x 2, sendo formado por quatro doses de Daminozide (0, 2000, 4000 e 6000 mg.L-1) e duas freqüências de aplicações (semanal e bissemanal). Os resultados mostraram que a cultivar Snowdon pode ser conduzida em vaso, porém, com aumento de ciclo e redução de até 28% na área da folha.

Produção de crisântemo (Dendranthema grandiflora Tzvelev.) 'Snowdon' em vaso I: doses e freqüências de aplicação de daminozide

The aim of this study was to investigate the response of potted chrysanthemum cv. Snowdon, to the growth retardant Daminozide, in terms of fenometric parameters. The study consisted of two experiments with five repetitions. The experiments were bifactorial 4 x 2, with four concentrations of Daminozide (0, 2,000, 4,000 and 6,000 mg.L-1) and two times of application (weekly and bi-weekly) of the product. Plant height, number of nodes, length of internodes, diameter of stems and inflorescences, length and diameter of floral peduncle were determinated. All concentrations and times of applications were able to reduce plant height, length of internodes, flower diameter and floral peduncle length. However, the diameter of the stem and floral peduncle were increased. The weekly application of 4,000 mg.L-1 Daminozide produced plants with the best quality within the commercial standards.

O trabalho teve como objetivo avaliar a resposta de crisântemo através da análise de parâmetros fenométricos, ao redutor de crescimento Daminozide, pulverizado na cultivar de crisântemo de corte "Snowdon", cultivada em vaso. O estudo foi formado por dois ensaios com cinco repetições, usando delineamento experimental inteiramente casualizado em esquema fatorial 4 x 2, sendo formado por quatro doses de Daminozide (0, 2.000, 4.000 e 6.000 mg.L-1) e duas freqüências de aplicações (semanal e bissemanal). Os resultados evidenciaram que as diferentes doses e freqüências de aplicações reduziram a altura da planta, o número de nós, o comprimento de entrenós, o diâmetro da inflorescência e o comprimento do pedúnculo floral. Entretanto, constatou-se aumento dos diâmetros da haste e do pedúnculo floral. Na dose 4.000 mg.L-1 aplicada semanalmente, produziram-se os vasos de melhor qualidade, com altura da planta nos padrões recomendados para comercialização.

Produção de crisântemo (Dendranthema grandiflora Tzvelev.) 'Snowdon' em vaso I: doses e freqüências de aplicação de daminozide

The aim of this study was to investigate the response of potted chrysanthemum cv. Snowdon, to the growth retardant Daminozide, in terms of fenometric parameters. The study consisted of two experiments with five repetitions. The experiments were bifactorial 4 x 2, with four concentrations of Daminozide (0, 2,000, 4,000 and 6,000 mg.L-1) and two times of application (weekly and bi-weekly) of the product. Plant height, number of nodes, length of internodes, diameter of stems and inflorescences, length and diameter of floral peduncle were determinated. All concentrations and times of applications were able to reduce plant height, length of internodes, flower diameter and floral peduncle length. However, the diameter of the stem and floral peduncle were increased. The weekly application of 4,000 mg.L-1 Daminozide produced plants with the best quality within the commercial standards.

O trabalho teve como objetivo avaliar a resposta de crisântemo através da análise de parâmetros fenométricos, ao redutor de crescimento Daminozide, pulverizado na cultivar de crisântemo de corte "Snowdon", cultivada em vaso. O estudo foi formado por dois ensaios com cinco repetições, usando delineamento experimental inteiramente casualizado em esquema fatorial 4 x 2, sendo formado por quatro doses de Daminozide (0, 2.000, 4.000 e 6.000 mg.L-1) e duas freqüências de aplicações (semanal e bissemanal). Os resultados evidenciaram que as diferentes doses e freqüências de aplicações reduziram a altura da planta, o número de nós, o comprimento de entrenós, o diâmetro da inflorescência e o comprimento do pedúnculo floral. Entretanto, constatou-se aumento dos diâmetros da haste e do pedúnculo floral. Na dose 4.000 mg.L-1 aplicada semanalmente, produziram-se os vasos de melhor qualidade, com altura da planta nos padrões recomendados para comercialização.