Knowledge and practice of Brazilian pediatricians on gastroesophageal reflux disease in infants / Conhecimento e prática de pediatras brasileiros sobre a doença do refluxo gastroesofágico em lactentes

OBJECTIVE: To assess the knowledge and practice of pediatricians about infants with physiological reflux and gastroesophageal reflux disease. METHODS: 140 pediatricians were interviewed during two scientific events in 2009 and 2010. The questions referred to two clinical cases of infants. One with symptoms of infant regurgitation (physiological reflux) and another with gastroesophageal reflux disease. RESULTS: Among 140 pediatricians, 11.4% (n=16) and 62.1% (n=87) would require investigation tests, respectively for infant regurgitation (physiological reflux) and gastroesophageal reflux disease. A series of upper gastrointestinal exams would be the first requested with a higher frequency. Medication would be prescribed by 18.6% (n=6) in the case of physiological reflux and 87.1% (n=122) in the case of gastroesophageal reflux disease. Prokinetic drugs would be prescribed more frequently than gastric acid secretion inhibitors. Sleeping position would be recommended by 94.2% (n=132) and 92.9% (n=130) of the respondents, respectively for the case of physiological reflux and gastroesophageal reflux disease; however, about half of the respondents would recommend the prone position. Only 10 (7.1%) of the pediatricians would exclude the cow's milk protein from the infants' diet. CONCLUSIONS: Approaches different from the international guidelines are often considered appropriate, especially when recommending a different position other than the supine and prescription of medication. In turn, the interviews enable us to infer the right capacity of the pediatricians to distinguish physiologic reflux and gastroesophageal reflux disease correctly. .

OBJETIVO: Avaliar o conhecimento e a prática de pediatras brasileiros na assistência ao lactente com refluxo fisiológico e doença do refluxo gastroesofágico. MÉTODOS: Foram entrevistados 140 médicos pediatras em dois eventos científicos em 2009 e 2010. As perguntas referiam-se a dois casos clínicos de lactentes, um com quadro compatível com regurgitação do lactente (refluxo fisiológico) e outro com doença do refluxo gastroesofágico. RESULTADOS: Dos 140 participantes, 11,4% (n=16) e 62,1% (n=87) solicitariam exame para lactentes, respectivamente, com refluxo fisiológico e doença do refluxo gastroesofágico. O primeiro exame solicitado com maior frequência seria a radiografia contrastada de esôfago, estômago e duodeno. Medicação seria prescrita por 18,6% (n=26) para o caso de refluxo fisiológico e 87,1% (n=122) para o caso de doença do refluxo gastroesofágico. Procinéticos seriam prescritos com maior frequência do que os redutores da secreção ácida gástrica. Prescrição de posição para dormir fez parte das recomendações de 94,2% (n=132) e 92,9% (n=130) dos entrevistados, respectivamente, para os casos de refluxo fisiológico e doença do refluxo gastroesofágico. Entretanto, cerca da metade dos entrevistados não recomendaria o decúbito dorsal. Prescrição de dieta de exclusão do leite de vaca para um lactente com quadro de doença do refluxo gastroesofágico seria feita por apenas 10 (7,1%) dos participantes. CONCLUSÕES: Condutas diferentes das diretrizes internacionais são frequentemente consideradas adequadas, especialmente quanto à recomendação de posição diferente do decúbito dorsal e prescrição de medicamentos. As respostas permitem inferir a capacidade de correta diferenciação entre refluxo fisiológico e doença do refluxo gastroesofágico. .

Vitamin D deficiency in pregnancy and its impact on the fetus, the newborn and in childhood / Deficiência de vitamina D na gravidez e o seu impacto sobre o feto, o recém-nascido e na infância

OBJECTIVE: Vitamin D deficiency (VDD) in pregnant women and their children is an important health problem with severe consequences for the health of both. Thus, the objectives of this review were to reassess the magnitude and consequences of VDD during pregnancy, lactation and infancy, associated risk factors, prevention methods, and to explore epigenetic mechanisms in early fetal life capable of explaining many of the non-skeletal benefits of vitamin D (ViD). DATA SOURCE: Original and review articles, and consensus documents with elevated level of evidence for VDD-related clinical decisions on the health of pregnant women and their children, as well as articles on the influence of ViD on epigenetic mechanisms of fetal programming of chronic diseases in adulthood were selected among articles published on PubMed over the last 20 years, using the search term VitD status, in combination with Pregnancy, Offspring health, Child outcomes, and Programming. DATA SYNTHESIS: The following items were analyzed: ViD physiology and metabolism, risk factors for VDD and implications in pregnancy, lactation and infancy, concentration cutoff to define VDD, the variability of methods for VDD detection, recommendations on ViD replacement in pregnant women, the newborn and the child, and the epigenetic influence of ViD. CONCLUSIONS: VDD is a common condition among high-risk pregnant women and their children. The routine monitoring of serum 25(OH)D3 levels in antenatal period is mandatory. Early preventive measures should be taken at the slightest suspicion of VDD in pregnant women, to reduce morbidity during pregnancy and lactation, as well as its subsequent impact on the fetus, the newborn and the child. .

OBJETIVO: Deficiência de vitamina D (DVD) nas gestantes e seus filhos é problema de saúde, com consequências graves à saúde de ambos. Assim, esta revisão visou reavaliar a magnitude e as consequências da DVD na gestação, lactação e infância, fatores de risco associados, métodos de prevenção, além de explorar os mecanismos epigenéticos na vida fetal capazes de explicar benefícios não-esqueléticos da vitamina D (ViD). FONTES DE DADOS: Selecionaram-se artigos originais, de revisão e consensos com nível elevado de evidência para decisões clínicas relacionadas à DVD na saúde das gestantes e seus filhos e artigos sobre sua ação sobre os mecanismos epigenéticos da programação fetal de doenças crônicas na vida adulta, publicados no PubMed nos últimos 20 anos, empregando-se VitD status, e em combinação com Pregnancy, Offspring health, Child outcomes e Programming. SÍNTESE DOS DADOS: Abordou-se fisiologia, metabolismo, fatores de risco para a DVD e implicações na gravidez, lactação e infância, concentração de corte para definir DVD, variabilidade de métodos na sua detecção, recomendações sobre a reposição de ViD nas gestantes, no recém-nascido e na criança, bem como sobre ter as influências epigenéticas da ViD. CONCLUSÕES: DVD é frequente entre gestantes de alto risco e seus filhos. Monitorar rotineiramente os níveis séricos de 25(OH)D3 no período antenatal é imperativo. Medidas preventivas precoces devem ser instituídas à menor suspeita de DVD na gestante, para reduzir morbidades durante a gestação e a lactação, bem como seu posterior impacto sobre o feto, o recém-nascido e na infância. .

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

[Study of the effect of light and heat on rosuvastatin calcium stability]

The effect of light on the stability of rosuvastatin was investigated by exposing rosuvastatin powder to white light [neon light] between 100 to 3000 Luxes for 3 days, according to health and safety requirements. In addition, five series of rosuvastatin powder was exposed, for 3 days, to different colors of light: White, blue, green, orange and red, with intensity 1000 Luxes. Also, the effect of heat on stability of rosuvastatin was studied. Three series were stored in the dark for 24 hours. The first series was stored without any additive under heat temperatures 30, 40, 50, 60 and 90°C with HR 100%. The second series was conducted under the same previous conditions of humidity and temperatures with 20% Calcium ascorbate as an anti oxidant. The third one was incubated in dry heat under the same temperatures, without any additive. All samples were analyzed using HPLC with a column C18 octadecyl, [250 mm X 4.6 mm]. The Studies have shown that rosuvastatin starts to deteriorate when exposed to white light, intensity of 200 Luxes for three days. The percentage of deteriorated rosuvastatin increases to reach more than 50% as light intensity increase to 3000 luxes. The study shows that the increase of temperature with the existence of humidity [relative humidity 100%] destroys rosuvastatin, and the addition of calcium ascorbat improves its stability in these conditions, while dry temperature up to 90° has no negative effect on its stability, and the lights [white, green, blue] destroy mainly Rosuvastatin, on the other side the lights red and orange have no any destroying effect on it, therefore we can use these lights [red and orange] successfully for lighting the laboratories and production sections during its preparation and its control in drugs factories for conservation its stability

Rational design, synthesis and computational structure-activity relationship of novel 3-[4-chlorophenyl]-5-[3-hydroxy-4-ethoxyphenyl]-4,5-dihydro-1H-pyrazole-1-carboxamide

Densely functionalized 3-[4-chlorophenyl]-5-[3-hydroxy-4-etoxyphenyl]-4, 5-dihydro-1H- pyrazole-1- carboxamide was synthesized in an expedient manner through specification and transamidation respectively, of ester-functionalized pyrazoles. This synthetic protocol allowed for three diversifying steps in which appendages on the pyrazole scaffold were adjusted to optimize inhibition of protein kinases. Computational design and study of novel 3-[4- chlorophenyl]-5-[3hydroxy-4-etoxyphenyl]-4, 5-dihydro-1H-pyrazole-1-carboxamide is reported. This computational prediction analysis will improve the understanding of candidate drugs and help in identifying its properties and effects on the human body. Simulation analysis of candidate drugs is necessary for providing clues about regulatory mechanisms, biochemical pathways and broader drug functions

Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor / 대한간학회지

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC.

Polyamines in inflammation and their modulation by conventional anti-inflammatory drugs.

Significant increase in polyamines levels in inflamed tissue was observed in the experimental animal models of inflammation. Treatment with dexamethasone positively modulated the levels of polyamines whereas non-steroidal drugs, diclofenac and valdecoxib negatively modulated their levels.

Comparative QSAR modeling of COX-2 inhibitor 1,2-diarylimidazoles using E-state and physicochemical parameters.

Considering importance of developing selective COX-2 inhibitors, COX-2 binding affinity data of 4-(2-aryl-1-imidazolyl)-phenyl methyl sulfones and sulfonamides (n = 83) have been modeled using electrotopological state (E-state) index as electronic parameter, hydrophobic substituent constant (pi) and molar refractivity (MR) of aryl ring substituents as lipophilic and steric parameters, respectively. Additionally, suitable dummy parameters have been used for the development of multiple regression equations in a stepwise manner. The study suggests that lipophilicity of ortho, meta and para substituents of the aryl ring increases the binding affinity, while molar refractivity (MR) of ortho and meta substituents of the aryl ring decreases the binding affinity. Again, electron-withdrawing substituents at meta and para positions of the aryl ring increase the binding affinity. Additionally, a 4-fluoro substituent on the aryl ring, a trifluoromethyl substituent at R position and simultaneous presence of 3-chloro and 4-methyl groups on the aryl ring are conducive to the binding affinity. Also, an amino substituent is preferred over a methyl group at R2 position suggesting preference of the sulfonamide moiety over the methyl sulfone moiety for the COX-2 binding affinity. Furthermore, importance of E-state values of different atoms in the generated relations suggests the influence of electron density distribution over the 1,2-diarylimidazole nucleus for the binding affinity. For this data set, E-state parameters perform better as electronic parameters in comparison to Hammett sigma parameters. When lipophilic whole molecular descriptor (ClogP) is used, instead of hydrophobic substituent constant (pi), the former performs better than the latter.

Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po).The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.