Estudo comparativo de fórmulas empregadas no cálculo de doses medicamentosas infantis

The present study was conducted to evaluate the utilization of Clark's, Salisbury and Penna's rules and the Body Surface Area (BSA) formula for calculation of pediatric drug dosage, as well as their reliability and viability in the clinical use. These rules are frequently cited in the literature, but much controversy still exists with regards to their use. The pediatric drug dosage was calculated by utilization of the aforementioned rules and using the drugs Paracetamol, Dipyrone, Diclofenac Potassium, Nimesulide, Amoxicillin and Erythromycin, widely employed in Pediatric Dentistry. Weight and body surface areas were considered of children with ages between 1 and 12 years old as well as the dosage for the adult. The pediatric dosages achieved were compared to the predetermined dosages in mg kg-1 herein-named standard dosages. The results were submitted to the parametric test ANOVA and to the Tukey test (pO presente estudo foi realizado com a finalidade de avaliar as fórmulas de Clark, Salisbury, Área da Superfície Corpórea (ASC) e Penna, quanto a sua confiabilidade e viabilidade de uso clínico para o cálculo de doses medicamentosas infantis, uma vez que tais fórmulas são freqüentemente citadas na literatura, mas muita controvérsia ainda existe com relação ao seu uso. As doses infantis foram calculadas utilizando as fórmulas descritas e os medicamentos Paracetamol, Dipirona, Diclofenaco de Potássio, Nimesulida, Amoxicilina e Eritromicina, largamente usados na clínica odontopediátrica. Foram considerados parâmetros como o peso e área da superfície corpórea de crianças com idades entre 1 e 12 anos e a dose para o adulto. As doses obtidas foram comparadas às doses em mg/kg consideradas como padrão de referência para os medicamentos. Os resultados foram submetidos ao teste paramétrico ANOVA e de Tukey (

Reduced caveolae density in arteries of SHR contributes to endothelial dysfunction and ROS production

Caveolae are plasma membrane invaginations enriched with high cholesterol and sphingolipid content; they also contain caveolin proteins in their structure. Endothelial nitric oxide synthase (eNOS), an enzyme that synthesizes nitric oxide (NO) by converting L-arginine to L-citrulline, is highly concentrated in plasma membrane caveolae. Hypertension is associated with decreased NO production and impaired endothelium-dependent relaxation. Understanding the molecular mechanisms that follow hypertension is important. For this study, we hypothesized that spontaneously hypertensive rat (SHR) vessels should have a smaller number of caveolae, and that the caveolae structure should be disrupted in these vessels. This should impair the eNOS function and diminish NO bioavailability. Therefore, we aimed to investigate caveolae integrity and density in SHR aortas and mesenteric arteries and the role played by caveolae in endothelium-dependent relaxation. We have been able to show the presence of caveolae-like structures in SHR aortas and mesenteric arteries. Increased phenylephrine-induced contractile response after treatment with dextrin was related to lower NO release. In addition, impaired acetylcholine-induced endothelium-dependent relaxation could be related to decreased caveolae density in SHR vessels. The most important finding of this study was that cholesterol depletion with dextrin induced eNOS phosphorylation at Serine1177 (Ser1177) and boosted reactive oxygen species (ROS) production in normotensive rat and SHR vessels, which suggested eNOS uncoupling. Dextrin plus L-NAME or BH4 decreased ROS production in aorta and mesenteric arteries supernatant's of both SHR and normotensive groups. Human umbilical vein endothelial cells (HUVECs) treated with dextrin confirmed eNOS uncoupling, as verified by the reduced eNOS dimer/monomer ratio. BH4, L-arginine, or BH4 plus L-arginine inhibited eNOS monomerization. All these results showed that caveolae structure and integrity are essential for endothelium-dependent relaxation. Additionally, a smaller number of caveolae is associated with hypertension. Finally, caveolae disruption promotes eNOS uncoupling in normotensive and hypertensive rat vessels and in HUVECs.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/22180-9, 2016/21239-0, 2017/14797-9]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [400.164/2014-0, 304.137/2014-6]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A mineralização dental e a atividade salivar estão reduzidas em filhotes de ratas espontaneamente hipertensas (SHR)

Several pathologies have been diagnosed in children of hypertensive mothers; however, some studies that evaluated the alterations in their oral health are not conclusive. This study analyzed the salivary gland activity and dental mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day-old SHR males and Wistar rats were studied. The salivary flow was evaluated by injection of pilocarpine, the protein concentration and salivary amylase activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel and dentin mineralization of the mandibular incisors was quantified with aid of the microhardness meter. The results were analyzed by the ANOVA or Student's t test (pDiversas patologias têm sido diagnosticadas em filhos de mães hipertensas, entretanto alguns estudos que avaliaram as possíveis alterações na saúde oral não são conclusivos. Neste trabalho foram analisadas a atividade das glândulas salivares e a mineralização dental de filhotes de ratas espontaneamente hipertensas (SHR). Ratos machos, com 30 dias de vida, SHR e Wistar, foram estudados. O fluxo salivar foi avaliado pela injeção de pilocarpina e a concentração de proteínas e atividade da amilase na saliva, pelo método de Lowry e método cinético a 405 nm, respectivamente. A mineralização do esmalte e dentina de incisivos inferiores foi quantificada através da medida da microdureza. Os resultados foram analisados pelo teste ANOVA ou t de Student's não pareado (

Qualidade de milho verde orgânico e convencional em atmosfera modificada

O presente trabalho teve por objetivo verificar a qualidade pós-colheita de cultivares de milho para colheita de espigas verdes provenientes de cultivo orgânico e convencional embaladas em bandejas de poliestireno expandido recoberto com filme de policloreto de vinila (PVC) em condições ambientais. Foram utilizadas espigas de milho provenientes de cultivos orgânico e convencional conduzidos na área experimental sediada no município de Andradina-SP. Seis bandejas por cultivar foram acondicionadas a 25,5 ± 2 °C e 60 ± 8 % UR por até 7 dias. As avaliações foram realizadas no início do experimento, 3 e 7 dias de armazenamento. O delineamento experimental utilizado foi o inteiramente casualizado, com três repetições, sendo os tratamentos dispostos em esquema fatorial 7 x 2 (cultivares: AG 1051, AG 4051, XB 7116, Cativerde, 20A55, BM 3061 e 2B587 e cultivo: orgânico e convencional). As unidades experimentais foram constituídas por cinco espigas em cada bandeja. Pelos resultados apresentados é possível concluir que a qualidade pós-colheita de espigas de milho verde das cultivares testadas não é influenciada pelo sistema de cultivo (convencional e orgânico)

Losartan improves alveolar bone dynamics in normotensive rats but not in hypertensive rats

Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. Objectives: To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. Methodology: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. Results: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. Conclusion: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension

Destabilisation, aggregation, toxicity and cytosolic mislocalisation of nucleophosmin regions associated with acute myeloid leukemia

Nucleophosmin (NPM1) is a multifunctional protein that is implicated in the pathogenesis of several human malignancies. To gain insight into the role of isolated fragments of NPM1 in its biological activities, we dissected the C-terminal domain (CTD) into its helical fragments. Here we focus the attention on the third helix of the NPM1-CTD in its wild-type (H3 wt) and AML-mutated (H3 mutA and H3 mutE) sequences. Conformational studies, by means of CD and NMR spectroscopies, showed that the H3 wt peptide was partially endowed with an a-helical structure, but the AML-sequences exhibited a lower content of this conformation, particularly the H3 mutA peptide. Thioflavin T assays showed that the H3 mutE and the H3 mutA peptides displayed a significant aggregation propensity that was confirmed by CD and DLS assays. In addition, we found that the H3 mutE and H3 mutA peptides, unlike the H3 wt, were moderately and highly toxic, respectively, when exposed to human neuroblastoma cells. Cellular localization experiments confirmed that the mutated sequences hamper their nucleolar accumulation, and more importantly, that the helical conformation of the H3 region is crucial for such a localization

Destabilisation, aggregation, toxicity and cytosolic mislocalisation of nucleophosmin regions associated with acute myeloid leukemia

Nucleophosmin (NPM1) is a multifunctional protein that is implicated in the pathogenesis of several human malignancies. To gain insight into the role of isolated fragments of NPM1 in its biological activities, we dissected the C-terminal domain (CTD) into its helical fragments. Here we focus the attention on the third helix of the NPM1-CTD in its wild-type (H3 wt) and AML-mutated (H3 mutA and H3 mutE) sequences. Conformational studies, by means of CD and NMR spectroscopies, showed that the H3 wt peptide was partially endowed with an a-helical structure, but the AML-sequences exhibited a lower content of this conformation, particularly the H3 mutA peptide. Thioflavin T assays showed that the H3 mutE and the H3 mutA peptides displayed a significant aggregation propensity that was confirmed by CD and DLS assays. In addition, we found that the H3 mutE and H3 mutA peptides, unlike the H3 wt, were moderately and highly toxic, respectively, when exposed to human neuroblastoma cells. Cellular localization experiments confirmed that the mutated sequences hamper their nucleolar accumulation, and more importantly, that the helical conformation of the H3 region is crucial for such a localization

Alveolar bone healing process in spontaneously hypertensive rats (SHR): A radiographic densitometry study

Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. Objectives: The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Material and Methods: Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. Results: The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. Conclusions: These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats

Comparative study of rules employed for calculation of pediatric drug dosage

The present study was conducted to evaluate the utilization of Clark's, Salisbury and Penna's rules and the Body Surface Area (BSA) formula for calculation of pediatric drug dosage, as well as their reliability and viability in the clinical use. These rules are frequently cited in the literature, but much controversy still exists with regards to their use. The pediatric drug dosage was calculated by utilization of the aforementioned rules and using the drugs Paracetamol, Dipyrone, Diclofenac Potassium, Nimesulide, Amoxicillin and Erythromycin, widely employed in Pediatric Dentistry. Weight and body surface areas were considered of children with ages between 1 and 12 years old as well as the dosage for the adult. The pediatric dosages achieved were compared to the predetermined dosages in mg kg-1 herein-named standard dosages. The results were submitted to the parametric test ANOVA and to the Tukey test (p<0,05). The antibiotics and Diclofenac provides acceptable utilization of the rules in pediatric dentistry, however for the Dipyrone, the dosages obtained by the rules suggest their clinical ineffectiveness. For the Paracetamol, the Penna's rule and the BSA formula should not be clinically employed, especially for children between 1 and 5 years old, once such dosages were much close to the hepatotoxic dosage of the drug. It can be concluded that the use of the rules for safe calculation of the pediatric drug dosage is possible and it depends on the used drug and age group