Nitrogen in common bean in no-tillage system over gramineae

An adequate supply of nitrogen is essential for high yield of common bean seeds; however, the responses to this nutrient in no-tillage systems can vary in function of the species and the amount of straw present. The aim of this research was to evaluate response of the common bean to N in no-tillage systems over maize, millet and Brachiaria brizantha crop residues. Three experiments were conducted, one for each gramineous species. The experimental design was a randomized block in a 5x2x2 factorial scheme, with five N doses (0, 30, 60, 90, 120 kg ha(-1)), in two distinct stadia during the vegetative development (3(rd) and 6(th) trifoliate leaf) and two common bean cultivars (IPR Juriti and Perola), with four replications. The IPR Juriti produced a greater number of pods per plant and showed lower mass per 100 seeds than Perola. It did not show variation in bean yield when the sidedressing N application was carried out in the 3(rd) or 6(th) trifoliate leaf stadia. Based on the obtained results, one concludes that the seed productivity of common beans increases linearly with N doses in a no-tillage system over maize residues.

DOSES OF INDOLBUTYRIC ACID IN THE ROOTING AND GROWTH OF EUCALYPT CUTTINGS (Eucalyptus urophylla)

This work aimed to evaluate the effect of different concentrations of IBA (indolbutyric acid) in the rooting and growth of Eucalyptus urophylla cuttings. The experimental design used was the randomized blocks, in factorial with an arrangement of split plots, with three concentrations of IBA (2.000; 5.000 and 8.000 mg L(-1)), two ways of the application of plant gowth regulators (paste and powder), and three period of evaluations (30, 45 and 60 days). The experiment was carried out in the Farm Buriti de Prata, an entreprise property of Souza Cruz, in the city of Prata - MG in 2003. After the preparation of the cuttings, patterned in 10 cm of length and 0.8 cm of diameter, those were immersed in mixtures of IBA for 10 seconds, in the forms of dry powder and paste and than planted in plastic tubes contening Plantmax substrate with vermiculite. The cuttings were transported to greenhouse with controled humidity, where they remained for 60 days. The variables studied were: height of plant in the 30(th), 45(th) and 60(th) days after seeding; fresh mass of the aerial part and roots. The IBA applied in powder form as well as in paste form, resulted in an greater seedling growth. To the 60 days, the seedlings presented greater growth, being significantly superior to the heights measured in other times of evaluation. The application of 2.000 mg L(-1) and 5,000 mg L(-1) resulted in significant increases on weight of fresh mass of the aerial part and root system.

Antioxidant Capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles

The antioxidant capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles was evaluated. The values of antioxidant capacities of compounds 2d and 2e were found to be, respectively, 2,700 +/- 150 and 3,135 +/- 230 TE by the ORAC method, corresponding to a significant antioxidant capacity.

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in an animal model

Background: Previous work showed that daily ingestion of an aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416, supplemented or not with isoflavones, reduced the total cholesterol and non-HDL-cholesterol levels, increased the high-density lipoprotein (HDL) concentration and inhibited the raising of autoantibody against oxidized low-density lipoprotein (ox-LDL Ab) and the development of atherosclerotic lesions. Objective: The aim of this study was to characterize the fecal microbiota in order to investigate the possible correlation between fecal microbiota, serum lipid parameters and atherosclerotic lesion development in rabbits with induced hypercholesterolemia, that ingested the aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416. Methods: The rabbits were randomly allocated to five experimental groups (n = 6): control (C), hypercholesterolemic (H), hypercholesterolemic plus unfermented soy product (HUF), hypercholesterolemic plus fermented soy product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented soy product (HIF). Lipid parameters and microbiota composition were analyzed on days 0 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment. The fecal microbiota was characterized by enumerating the Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Enterobacteria and Clostridium spp. populations. Results: After 60 days of the experiment, intake of the probiotic soy product was correlated with significant increases (P < 0.05) on Lactobacillus spp., Bifidobacterium spp. and Enterococcus spp. and a decrease in the Enterobacteria population. A strong correlation was observed between microbiota composition and lipid profile. Populations of Enterococcus spp., Lactobacillus spp. and Bifidobacterium spp. were negatively correlated with total cholesterol, non-HDL-cholesterol, autoantibodies against oxidized LDL (ox-LDL Ab) and lesion size. HDL-C levels were positively correlated with Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. populations. Conclusion: In conclusion, daily ingestion of the probiotic soy product, supplemented or not with isoflavones, may contribute to a beneficial balance of the fecal microbiota and this modulation is associated with an improved cholesterol profile and inhibition of atherosclerotic lesion development.

Ultrasound Irradiation Promoted Large-Scale Preparation in Aqueous Media and Antioxidant Activity of Azoles

The scaled-up preparation of 1H-pyrazole, 1-phenylpyrazole and isoxazole via sonocatalysis is reported. The products were isolated in good yields in short time reaction. These compounds had been assayed for antioxidant activity by ORAC and DPPH methodologies. The results showed that only 1-phenylpyrazole presented good antioxidant activity compared with Trolox(R).

Dietary glutamine supplementation increases the activity of peritoneal macrophages and hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guerin

Infants who are breast-fed have been shown to have a lower incidence of certain infectious diseases compared with formula-fed infants. Glutamine is one of the most abundant amino acids found in maternal milk and it is essential for the function of immune system cells such as macrophages. The purpose of this study was to investigate the effect of glutamine supplementation on the function of peritoneal macrophages and on hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guerin (BCG). Mice were wearied at 14 d of age and distributed to 2 groups and fed either a glutamine-free diet (n = 16) or a glutamine-supplemented diet (+Gln (n = 16). Both diets were isonitrogenous (with addition of a mixture of nonessential amino acids) and isocaloric. At d 21, 2 subgroups of mice (n = 16) were intraperitoneally injected with BCG and all mice were killed at d 28. Plasma, muscle and liver glutamine concentrations and muscle glutamine synthetase activity were not affected by diet or inoculation with BCG. The +GIn diet led to increased leukocyte and lymphocyte counts in the peripheral blood (P < 0.05) and granulocyte and lymphocyte counts in the bone marrow and spleen (P < 0.05). The +GIn diet increased spreading and adhesion capacities, hydrogen peroxide, nitric oxide, and tumor necrosis factor-alpha (TNF alpha) syntheses and the phagocytic and fungicidal activity of peritoneal macrophages (P < 0.05). The interaction between the +GIn diet and BCG inoculation increased the area under the curve of interleukin (IL)-1 beta and TNF alpha syntheses (P < 0.05). In conclusion, the intake of glutamine increases the function of peritoneal macrophages and hemopoiesis in early-weaned and BCG-inoculated mice. These data have important implications for the design of breast milk substitutes for human infants.

Comparison of the Rupture and Disintegration Tests for Soft-Shell Capsules

The USP General Chapter < 2040 > Disintegration and Dissolution of Dietary Supplements introduced a rupture test as a performance test of soft-shell capsules. Traditionally, the disintegration test was used for determining the disintegration time of all solid oral dosage forms. The aim of this investigation was to investigate differences between the rupture test and the disintegration test using soft-shell capsules. Five different soft-shell capsule products were chosen based on their filling contents and treated to simulate a production deficiency. The study design compared capsules as received with capsules that were treated by coating them with the liquid contents of another capsule. The capsules were incubated at room temperature and at 40 degrees C. The tests were repeated after two weeks, and at each time point, twelve capsules of each product were tested using the rupture and the disintegration tests. Six capsules were tested untreated, while the other six capsules were treated. Rupture and disintegration times were recorded as dependent variables in each experiment. Thedata were analyzed using ANOVA. According to the USP definition for disintegration, the rupture of a soft-shell capsule can be seen as fulfilling the disintegration criterion if the capsule contents is a semisolid or liquid. Statistical analysis showed no advantage of the rupture test over the disintegration test. On a product-by-product basis, both tests were sensitive to certain investigated parameters. A noticeable difference between both tests was that in most cases, the rupture test reached the defined endpoint faster than the disintegration test. Soft-shell capsules that are subject to a Quality by Design approach should be tested with both methods to determine which performance test is the most appropriate test for a specific product.

Investigation of the Performance of the Disintegration Test for Dietary Supplements

The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, < 701 > and < 2040 >. Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and one with a 1,500-mL volume. The disintegration data were analyzed using ANOVA for the following factors: beaker size, equipment (App A and B) and condition (with/without disk). Two tablet products were not sensitive to any changes in the test conditions or equipment configurations. One product was only partially sensitive to the test conditions. The other products showed impact on the disintegration time for all test conditions. The results revealed that these tablet products might pass or fail current USP disintegration requirements depending on the equipment configuration. Similar results were obtained for the two investigated capsule formulations. One product might fail current USP disintegration requirements if the large beaker was used, but might pass the disintegration requirements when the small beaker was used. Hydroxy propyl methyl cellulose capsules were mostly influenced if sodium instead of a potassium buffer was used as the immersion medium. The results demonstrate that the current harmonized ICH specifications for the disintegration test are insufficient to make the disintegration test into reliable test for dietary supplements.

Molecular Modeling Suggests Cruzain Specificity for Peptide Primaquine Prodrugs

Chagas` disease, infection caused by the protozoan Trypanosoma cruzi, is an important, social and medical ailment in the Latin America. This disease is endemic in 21 countries, mostly Latin America countries, with more than 300,000 new cases every year and about 16-18 million infected people. Current therapy is not effective in the chronic phase of the disease. Thus, new and better drugs are urgently needed. In this sense, the in vitro activity of primaquine (PQ) was reported. Based on this, peptide prodrugs of primaquine containing dipeptides - lysine-arginine (LysArg), phenylalanine-alanine (PheAla) and phenylalanine-arginine (PheArg) -- as carriers, were designed to be selectively cleaved by cruzain, a specific cysteine protease of T. cruzi. The prodrugs have shown to be active against tripomastigote forms according to this order: LysArg-PQ> PheAla-PQ> PheArg-PQ. The molecular mechanism of action considered a probable nucleophilic attack of the catalytic residue of cruzain (Cys25) on the respective prodrug amide carbonyl carbon, releasing PQ. In order to test this hypothesis, molecular modeling studies were performed, physicochemical parameters and stereoelectronic features calculated by using the AM1 semi-empirical method suggest that the amide carbonyl carbon is favorable for cleavage, where the LysArg showed the most electronic reactive and sterically disposable, leading to the prodrug release and action. In addition, the docking study indicates the occurrence of specific interactions between prodrugs and the pockets S1 and S2 of cruzain through the dipeptides carriers, being the distance between cruzain Cys25 and the amide carbonyl group related to the biological activity of the prodrugs.

Determination of Atropine Enantiomers in Ophthalmic Solutions by Liquid Chromatography Using a Chiral AGP (R) Column

Many therapeutic agents are commercialized under their racemic form. The enantiomers can show differences in the pharmacokinetic and pharmacodynamic profile. The use of a pure enantiomer in pharmaceutical formulations may result in a better therapeutic index and fewer adverse effects. Atropine, an alkaloid of Atropa belladonna, is a racemic mixture of l-hyoscyamine and d-hyoscyamine. It is widely used to dilate the pupil. To quantify these enantiomers in ophthalmic solutions, an HPLC method was developed and validated using a Chiral AGP (R) column at 20 degrees C. The mobile phase consisted of a buffered phosphate solution (containing 10 mM 1-octanesulfonic acid sodium salt and 7.5 mM triethylamine, adjusted to pH 7.0 with orthophosphoric acid) and acetonitrile (99 + 1, v/v). The flow rate was 0.6 mL/min, with UV detection at 205 nm. In the concentration range of 14.0-26.0 mu g/mL, the method was found to be linear (r > 0.9999), accurate (with recovery of 100.1-100.5%), and precise (RSD system: <= 0.6%; RSD intraday: <= 1.1%; RSD interday: <= 0.9%). The method was specific, and the standard and sample solutions were stable for up to 72 h. The factorial design assures robustness with a variation of +/-10% in the mobile phase components and 2 degrees C of column temperature. The complete validation, including stress testing and factorial design, was studied and is presented in this research.

Rational Design and 3D-Pharmacophore Mapping of 5 `-Thiourea-Substituted alpha-Thymidine Analogues as Mycobacterial TMPK Inhibitors

Thymidine monophosphate kinase (TMPK) has emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. In this study the receptor-independent (RI) 4D-QSAR formalism has been used to develop QSAR models and corresponding 3D-pharmacophores for a set of 5`-thiourea-substituted alpha-thymidine inhibitors. Models were developed for the entire training set and for a subset of the training set consisting of the most potent inhibitors. The optimized (RI) 4D-QSAR models are statistically significant (r(2) = 0.90, q(2) = 0.83 entire set, r(2) = 0.86, q(2) = 0.80 high potency subset) and also possess good predictivity based on test set predictions. The most and least potent inhibitors, in their respective postulated active conformations derived from the models, were docked in the active site of the TMPK crystallographic structure. There is a solid consistency between the 3D-pharmacophore sites defined by the QSAR models and interactions with binding site residues. This model identifies new regions of the inhibitors that contain pharmacophore sites, such as the sugar-pyrimidine ring structure and the region of the 5`-arylthiourea moiety. These new regions of the ligands can be further explored and possibly exploited to identify new, novel, and, perhaps, better antituberculosis inhibitors of TMPKmt. Furthermore, the 3D-pharmacophores defined by these models can be used as a starting point for future receptor-dependent antituberculosis drug design as well as to elucidate candidate sites for substituent addition to optimize ADMET properties of analog inhibitors.

Double-blind, randomized, placebo-controlled trial of a cream containing the Stryphnodendron adstringens (Martius) Coville bark extract for suppressing terminal hair growth

Background Excess of terminal hair can be defined as excessive hair that appears in male-like pattern in women. Some experts consider this condition as a result of an atypical relationship between levels of circulating androgens and sensitivity of androgen receptors in hair follicles to circulating androgens. Aims The aim of this research work was to evaluate the efficacy of a topical treatment for suppressing terminal hair growth of a cream containing 6.0% of the Stryphnodendron adstringens bark extract. Study design and subjects Study was randomized, double-blind and placebo-controlled. Subjects with excess of terminal hair were randomized to placebo and to the active treatment (cream with 6.0% of the extract). Evaluation was performed before and after 6 months, and subjects were photographed in each time. Clinical examination was carried out with the same physicians and in accordance with the Ferriman-Gallwey (FG) score. Results Benefits of the cream containing S. adstringens bark extract was observed in 60.98% (P < 0.001) of the subjects. FG score changed from 4 to 3 in the placebo group compared to 4-2 in the active. The cream suppressed the terminal hair growth and diminished the number of terminal hair. Subjects also described the reduction of skin hyperpigmentation, folliculitis and acne. Adverse events were not verified by physicians or patients. Conclusions The cream with 6.0% of the S. adstringens bark extract was effective on the reduction and on the reversion of the terminal hair excess, being considered a new promissory product for such finality.

Influence of Urea, Isopropanol, and Propylene Glycol on Rutin In Vitro Release from Cosmetic Semisolid Systems Estimated by Factorial Design

Rutin, one of the major flavonoids found in an assortment of plants, was reported to act as a sun protection factor booster with high anti-UVA defense, antioxidant, antiaging, and anticellulite, by improvement of the cutaneous microcirculation. This research work aimed at evaluating the rutin in vitro release from semisolid systems, in vertical diffusion cells, containing urea, isopropanol and propylene glycol, associated or not, according to the factorial design with two levels with center point. Urea (alone and in association with isopropanol and propylene glycol) and isopropanol (alone and in association with propylene glycol) influenced significant and negatively rutin liberation in diverse parameters: flux (g/cm2.h); apparent permeability coefficient (cm/h); rutin amount released (g/cm2); and liberation enhancement factor. In accordance with the results, the presence of propylene glycol 5.0% (wt/wt) presented statistically favorable to promote rutin release from this semisolid system with flux = 105.12 8.59 g/cm2.h; apparent permeability coefficient = 7.01 0.572 cm/h; rutin amount released = 648.80 53.01 g/cm2; and liberation enhancement factor = 1.21 0.07.

Emulsified systems based on glyceryl monostearate and potassium cetyl phosphate: Scale-up and characterization of physical properties

introducing a pharmaceutical product on the market involves several stages of research. The scale-up stage comprises the integration of previous phases of development and their integration. This phase is extremely important since many process limitations which do not appear on the small scale become significant on the transposition to a large one. Since scientific literature presents only a few reports about the characterization of emulsified systems involving their scaling-up, this research work aimed at evaluating physical properties of non-ionic and anionic emulsions during their manufacturing phases: laboratory stage and scale-up. Prototype non-ionic (glyceryl monostearate) and anionic (potassium cetyl phosphate) emulsified systems had the physical properties by the determination of the droplet size (D[4,3 1, mu m) and rheology profile. Transposition occurred from a batch of 500-50,000 g. Semi-industrial manufacturing involved distinct conditions: intensity of agitation and homogenization. Comparing the non-ionic and anionic systems, it was observed that anionic emulsifiers generated systems with smaller droplet size and higher viscosity in laboratory scale. Besides that, for the concentrations tested, augmentation of the glyceryl monostearate emulsifier content provided formulations with better physical characteristics. For systems with potassium cetyl phosphate, droplet size increased with the elevation of the emulsifier concentration, suggesting inadequate stability. The scale-up provoked more significant alterations on the rheological profile and droplet size on the anionic systems than the non-ionic. (C) 2008 Elsevier B.V. All rights reserved.

Optimization of Pothomorphe umbellata (L.) Miquel topical formulations using experimental design

Pothomorphe umbellata is a native plant widely employed in the Brazilian popular medicine. This plant has been shown to exert a potent antioxidant activity on the skin and to delay the onset and reduce the incidence of UVB-induced skin damage and photoaging. The aim of this work was to optimize the appearance, the centrifuge stability and the permeation of emulsions containing R umbellata (0. 1% 4-nerolidylchatecol). Experimental design was used to study ternary mixtures models with constraints and graphical representation by phase diagrams. The constraints reduce the possible experimental domain, and for this reason, this methodology offers the maximum information while requiring the minimum investment. The results showed that the appearance follows a linear model, and that the aqueous phase was the principal factor affecting the appearance; the centrifuge stability parameter followed a mathernatic quadratic model and the interactions between factors produced the most stable emulsions; skin permeation was improved by the oil phase, following a linear model generated by data analysis. We propose as optimized P. umbellata formulation: 68.4% aqueous phase, 26.6% oil phase and 5.0% of self-emulsifying phase. This formulation displayed an acceptable compromise between factors and responses investigated. (c) 2007 Elsevier B.V. All rights reserved.