Fluoride dose response in pH-cycling models using bovine enamel

The aim of this study was to establish methodologies for verification of the fluoride solution dose-response relationship using bovine enamel and pH-cycling models. Six models of the cariogenic challenge were performed, varying the time of demineralization and pH, time of remineralization, composition of de- and remineralization solutions, frequency and time of application of treatment solutions and pH-cycling duration. For the evaluation of the fluoride effect on caries dynamics, two proposed models provided for improvement in standardization of methods leading to a higher level of precision, demonstrating a dose response between treatments with regard to surface microhardness and Delta Z. For the evaluation of the fluoride effect on enamel remineralization, the addition of fluoride to the de- and remineralization solutions and the reduction of frequency and time of application of fluoride solutions led to a more suitable pH-cycling model. Copyright (C) 2005 S. Karger AG, Basel.

Dose response relationship of droplet applications for the leaf-specific weed control in vegetable crops

As a prelude to leaf-specific weed control using droplets targeted by a robotic weeder, amounts of herbicide required to control individual weed seedlings were estimated. Roundup Biactive was applied at doses equivalent to 1/128th to four times the recommended rate in addition to undiluted Roundup and water controls. Based on the mean ground cover of the seedlings, the recommended dose (1.5 l ha 1) was estimated and droplets were applied to individual plants by micropipette. All treatments contained 1% AS 500 SL, Agromix (adjuvant). Three weeks after application dry weights (DW) of each seedling was recorded. DW reductions of 50% were achieved in the five species tested at less than the recommended rate whereas only in one species was a 90% reduction obtained at that rate. In Galium aparine for example, 19.3 μg of glyphosate reduced DW per plant by 90% compared to the recommended dose of 8.4 μg.

Extragenic Suppressors of the Arabidopsis gai Mutation Alter the Dose-Response Relationship of Diverse Gibberellin Responses1

Active gibberellins (GAs) are endogenous factors that regulate plant growth and development in a dose-dependent fashion. Mutant plants that are GA deficient, or exhibit reduced GA responses, display a characteristic dwarf phenotype. Extragenic suppressor analysis has resulted in the isolation of Arabidopsis mutations, which partially suppress the dwarf phenotype conferred by GA deficiency and reduced GA-response mutations. Here we describe detailed studies of the effects of two of these suppressors, spy-7 and gar2–1, on several different GA-responsive growth processes (seed germination, vegetative growth, stem elongation, chlorophyll accumulation, and flowering) and on the in planta amounts of active and inactive GA species. The results of these experiments show that spy-7 and gar2–1 affect the GA dose-response relationship for a wide range of GA responses and suggest that all GA-regulated processes are controlled through a negatively acting GA-signaling pathway.

Metodologia para determinar a relação dose-resposta de produtos fluoretados utilizando esmalte bovino e modelo de ciclagem de pH

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Copper and human health: biochemistry, genetics, and strategies for modeling dose-response relationships

Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Acute and chronic methylphenidate dose-response assessment on three adolescent male rat strains.

Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to compare whether there were strain differences. An automated, computerized, open-field activity monitoring system was used to study the dose-response characteristics of acute and repeated MPD administration throughout the 11-day experimental protocol. Results showed that all three adolescent rat groups exhibited dose-response characteristics following acute and chronic MPD administration, as well as strain differences. These strain differences depended on the MPD dose and locomotor index. Chronic treatment of MPD in these animals did not elicit behavioral sensitization, a phenomenon described in adult rats that is characterized by the progressive augmentation of the locomotor response to repeated administration of the drug. These results suggest that the animal's age at time of drug treatment and strain/genetic variability play a crucial role in the acute and chronic effect of MPD and in the development of behavioral sensitization.

Efeito de vernizes fluoretados suplementados com trimetafosfato de sódio na desmineralização e remineralização do esmalte bovino: estudos in vitro e in situ

Pós-graduação em Ciência Odontólogica - FOA

Validação de um modelo de ciclagem de pH para verificar a relação dose-resposta de materiais que liberam flúor na desmineralização e remineralização in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

In situ protocol for the detemination of dose-response effect of low-fluoride dentifrices on enamel remineralization

No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F]) on bovine enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol) separately for 3 and 7 days. Surface hardness (SH), integrated subsurface hardness (AKHN) and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p<0.05). Results: Dose-response relationships were verified between [F] in dentifrices and SH, AKHN and enamel [F]. Higher correlation coefficients between enamel [F] and SH and AKHN were obtained for the 3-day period. Significant differences in SH and AKHN were observed among all groups for the 3-day period, but not between 0-275, 275-550, and 550-1,100 mu g F/g dentifrices for the 7-day period, nor between 3- and 7-day periods for the 1,100 mu g F/g groups. Conclusions: Considering that the peak remineralization capacity of the conventional dentifrice (1,100 mu g F/g) was achieved in 3 days, this experimental period could be used in future studies assessing new dentifrice formulations, especially at low-fluoride concentrations.

In vitro Remineralizing Effect of Fluoride Varnishes Containing Sodium Trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anticariogenic potencial of acidulate solutions with low fluoride concentration

Objetives: The aim of this study was to verify the anticariogenic effect of acidulate solutions with low NaF concentration, using pH-cycling model and bovine enamel. Material and Methods: Enamel blocks were submitted to the surface microhardness (SMH) test and randomly divided in 12 experimental and one placebo groups. The blocks were submitted to pH cycling for 7 days, with daily applications once/day of 0.05% NaF and 0.1% NaF and twice/day of 0.02% NaF solutions. Four different pH: 4.0, 5.0, 6.0 and 7.0 were used. Next, SMH test was again used to determine the surface microhardness percentage change (%SMH). Data obtained for %SMH were homogeneous and passed through variance analyses and Tukey's test (5%) as far as fluoride concentrations and pH. Results: The results showed that pH influenced %SMH in 0.02% NaF and 0.05% NaF solutions with pH 4.0, which had less mineral loss compared to pH 7.0 (p<0.05). The 0.02% NaF - pH 4.0, and 0.05% NaF – pH 7.0 groups showed similar results (p>0.05). A dose-response relationship was observed among the tested solutions, with better anticariogenic effect for the 0.1% NaF solution. Conclusion: The results suggest that the addition of citric acid to acidulate mouth rinses reduce mineral loss.

Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat

Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 mug/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 mug/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two-to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.