Host-guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), Hydroxypropyl-beta-cyclodextrin (HP-beta-CD), Dimethyl-beta-cyclodextrin (DM-beta-CD) and gamma-cyclodextrin (gamma-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand-Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-beta-CD > beta-CD > alpha-CD > HP-beta-CD > gamma-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.

Validation of a gas chromatographic method to quantify sesquiterpenes in copaiba oils

Copaifera species (Leguminoseae) are popularly known as ""copaiba"" or ""copaiva"". The oleoresins obtained from the trunk of these species have been extensively used in folk medicine and are commercialized in Brazil as crude oil and in several pharmaceutical and cosmetic products. This work reports a complete validated method for the quantification of beta-caryophyllene, alpha-copaene, and alpha-humulene in distinct copaiba oleoresins available commercially. Thus, essential oil samples (100 mu L) were dissolved in 20 mL of hexanes containing internal standard (1,2,4,5-tetramethylbenzene, 3.0 mM) in a 25 mL glass flask. A 1 mu L aliquot was injected into the GC-FID system. A fused-silica capillary column HP-5, coated with 5% phenylmethylsiloxane was used for this study. The developed method gave a good detection response with linearity in the range of 0.10-18.74 mM. Limits of detection and quantitation variety ranged between 0.003 and 0.091 mM. beta-Caryophyllene, alpha-copaene, and alpha-humulene were recovered in a range from 74.71% to 88.31%, displaying RSD lower than 10% and relative errors between -11.69% and -25.30%. Therefore, this method could be considered as an analytical tool for the quality control of different Copaifera oil samples and its products in both cosmetic and pharmaceutical companies. (C) 2010 Elsevier B.V. All rights reserved.

IMAGE QUANTIFICATION FOR RADIATION DOSE CALCULATIONS-LIMITATIONS AND UNCERTAINTIES

Radiation dose calculations in nuclear medicine depend on quantification of activity via planar and/or tomographic imaging methods. However, both methods have inherent limitations, and the accuracy of activity estimates varies with object size, background levels, and other variables. The goal of this study was to evaluate the limitations of quantitative imaging with planar and single photon emission computed tomography (SPECT) approaches, with a focus on activity quantification for use in calculating absorbed dose estimates for normal organs and tumors. To do this we studied a series of phantoms of varying complexity of geometry, with three radionuclides whose decay schemes varied from simple to complex. Four aqueous concentrations of (99m)Tc, (131)I, and (111)In (74, 185, 370, and 740 kBq mL(-1)) were placed in spheres of four different sizes in a water-filled phantom, with three different levels of activity in the surrounding water. Planar and SPECT images of the phantoms were obtained on a modern SPECT/computed tomography (CT) system. These radionuclides and concentration/background studies were repeated using a cardiac phantom and a modified torso phantom with liver and ""tumor"" regions containing the radionuclide concentrations and with the same varying background levels. Planar quantification was performed using the geometric mean approach, with attenuation correction (AC), and with and without scatter corrections (SC and NSC). SPECT images were reconstructed using attenuation maps (AM) for AC; scatter windows were used to perform SC during image reconstruction. For spherical sources with corrected data, good accuracy was observed (generally within +/- 10% of known values) for the largest sphere (11.5 mL) and for both planar and SPECT methods with (99m)Tc and (131)I, but were poorest and deviated from known values for smaller objects, most notably for (111)In. SPECT quantification was affected by the partial volume effect in smaller objects and generally showed larger errors than the planar results in these cases for all radionuclides. For the cardiac phantom, results were the most accurate of all of the experiments for all radionuclides. Background subtraction was an important factor influencing these results. The contribution of scattered photons was important in quantification with (131)I; if scatter was not accounted for, activity tended to be overestimated using planar quantification methods. For the torso phantom experiments, results show a clear underestimation of activity when compared to previous experiment with spherical sources for all radionuclides. Despite some variations that were observed as the level of background increased, the SPECT results were more consistent across different activity concentrations. Planar or SPECT quantification on state-of-the-art gamma cameras with appropriate quantitative processing can provide accuracies of better than 10% for large objects and modest target-to-background concentrations; however when smaller objects are used, in the presence of higher background, and for nuclides with more complex decay schemes, SPECT quantification methods generally produce better results. Health Phys. 99(5):688-701; 2010

Effects of different mechanical ventilation strategies on the mucociliary system

To evaluate the effects of different mechanical ventilation (MV) strategies on the mucociliary system. Experimental study. Twenty-seven male New Zealand rabbits. After anesthesia, animals were tracheotomized and ventilated with standard ventilation [tidal volume (Vt) 8 ml/kg, positive end expiratory pressure (PEEP) 5 cmH(2)O, flow 3 L/min, FiO(2) 0.4] for 30 min. Next, animals were randomized into three groups and ventilated for 3 h with low volume (LV): Vt 8 ml/kg, PEEP 5 cmH(2)O, flow 3 L/min (n = 6); high volume (HV): Vt 16 ml/kg, PEEP 5 cmH(2)O, flow 5 L/min (n = 7); or high pressure (HP): Ppeak 30 cmH(2)O, PEEP 12 cmH(2)O (n = 8). Six animals (controls) were ventilated for 10 min with standard ventilation. Vital signals, blood lactate, and respiratory system mechanics were verified. Tracheal tissue was collected before and after MV. Lung and tracheal tissue sections were stained to analyze inflammation and mucosubstances by the point-counting method. Electron microscopy verified tracheal cell ultrastructure. In situ tracheal ciliary beating frequency (CBF), determined using a videoscopic technique, and tracheal mucociliary transport (TMCT), assessed by stereoscopic microscope, were evaluated before and after MV. Respiratory compliance decreased in the HP group. The HV and HP groups showed higher lactate levels after MV. Macroscopy showed areas of atelectasis and congestion on HV and HP lungs. Lung inflammatory infiltrate increased in all ventilated groups. Compared to the control, ventilated animals also showed a reduction of total and acid mucus on tracheal epithelium. Under electron microscopy, injury was observed in the ciliated cells of the HP group. CBF decreased significantly after MV only in the HP group. TMCT did not change significantly in the ventilated groups. Different MV strategies induce not only distal lung alterations but also morphological and physiological tracheal alterations leading to mucociliary system dysfunction.

Rhipicephalus (Boophilus) microplus: Distinct acute phase proteins vary during infestations according to the genetic composition of the bovine hosts, Bos taurus and Bos indicus

Tick bites may trigger acute phase responses. Positive and negative acute phase proteins were measured in infested cattle genetically resistant and susceptible to ticks. During heavier infestations levels of haptoglobin increased significantly in susceptible bovines; levels of serum amyloid A increased in resistant bovines; levels of alpha-l-acid glycoprotein decreased significantly in resistant bovines; levels of transferrin decreased significantly in susceptible bovines. In conclusion, tick infestations trigger acute phase responses and enhancement of specific acute phase proteins differs according to the genetic composition of hosts. Acute phase proteins may constitute useful biological signatures for monitoring the stress induced by tick infestations. (c) 2007 Elsevier Inc. All rights reserved.

Protein Intake during Weight Loss Influences the Energy Required for Weight Loss and Maintenance in Cats

The effects of 2 diets with different protein contents on weight loss and subsequent maintenance was assessed in obese cats. The control group [Cc; n = 8; body condition score (BCS) = 8.6 +/- 0.2] received a diet containing 21.4 g crude protein (CP)/MJ of metabolizable energy and the high-protein group (HP; n = 7; BCS = 8.6 +/- 0.2) received a diet containing 28.4 g CP/MJ until the cats achieved a 20% controlled weight loss (0.92 +/- 0.2%/wk). After the weight loss, the cats were all fed a diet containing 28.0 g CP/MJ at an amount sufficient to maintain a constant body weight (MAIN) for 120 d. During weight loss, there was a reduction of lean mass in Cc (P < 0.01) but not in HIP cats and a reduction in leptinemia in both groups (P < 0.01). Energy intake per kilogram of metabolic weight (kg(-0.40)) to maintain the same rate of weight loss was lower (P < 0.04) in the Co (344 +/- 15.9 kJ.kg(-0.40).d(-1)) than in the HP group (377 +/- 12.4 kJ.kg-(0.40).d(-1)). During the first 40 d of MAIN, the energy requirement for weight maintenance was 398.7 +/- 9.7 kJ.kg(-0.40).d(-1) for both groups, corresponding to 73% of the NRC recommendation. The required energy gradually increased in both groups (P < 0.05) but at a faster rate in HP; therefore, the energy consumption during the last 40 d of the MAIN was higher (P < 0.001) for the HP cats (533.8 +/- 7.4 kJ.kg(-0.40).d(-1)) than for the control cats (462.3 +/- 9.6 kJ.kg(-0.40).d(-1)). These findings suggest that HIP diets allow a higher energy intake to weight loss in cats, reducing the intensity of energy restriction. Protein intake also seemed to have long-term effects so that weight maintenance required more energy after weight loss. J. Nutr, 139: 855-860, 2009.

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension

Background: Abnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C(-) (1562) T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension. Methods: We studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C(- 1562) T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program. Results: For the g.-90(CA)13-25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.-1562C>T polymorphism were more commonly found in GH subjects compared with the HP group (both P<0.05). Conversely, we found no differences in genotypes or allele distributions for the g.-1562C>T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group. Conclusions: The C(- 1562) T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP. (C) 2010 Elsevier B.V. All rights reserved.

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with GH and 94 with PE). When white and non-white pregnant women were considered together, no significant differences were found in the distributions of VEGF genotypes or haplotypes (P > 0.05) in the three groups. However, with only white subjects, significant differences were found in genotypes distributions for two (C-2578A and G-634C) VEGF polymorphisms (both P < 0.05) between the HP and the PE groups. Importantly, the haplotype including the variants C-2578, G-1154 and C-634, which is associated with higher VEGF gene expression, was less common in the PE group compared with the HP group (4% versus 16%; P = 0.0047). However, we found no significant differences in VEGF haplotypes distributions when the HP and GH groups were compared (P > 0.05). These findings suggest a protective effect for the `C-2578, G-1154 and C-634` haplotype against the development of PE, but no major effects of VEGF gene variants on susceptibility to GH.

The Effect of Fluoride Therapies on the Morphology of Bleached Human Dental Enamel

The aim of this in vitro study was to evaluate qualitatively the surface morphology of enamel bleached with 35% hydrogen peroxide (HP) followed by application of fluoridated agents. Forty intact pre molars were randomly distributed into four groups (n = 10), treated as follows: Group I (control group) remained stored in artificial saliva at 37 degrees C, Group II - 35% HP; Group III - 35% HP + acidulated fluoride (1.23%) and Group IV - 35% HP + neutral fluoride (2%). The experimental groups received three applications of bleaching gel and after the last application all specimens were polished. This procedure was repeated after 7 and 14 days, and during the intervals of applications, the specimens were stored in artificial saliva at 37 degrees C. Scanning electron microscopy (SEM) analysis showed superficial irregularities and porosities to varying degrees in bleached enamel compared to control group. Sample evaluation was made by attributing scores, and data were statistically analyzed using Kruskal-Wallis and Dunn tests (P < 0.05). SEM qualitative investigation demonstrated that 35% hydrogen peroxide affected human dental enamel morphology, producing porosities, depressions, and superficial irregularities at various degrees. These morphological changes were higher after the application of 1.23% acidulated fluoride gel. Microsc. Res. Tech. 74:512-516, 2011. (C) 2010 Wiley-Liss, Inc.

Effect of different surface treatments on the repair bond strength of indirect composites

Purpose: To evaluate the tensile bond strength of indirect composites repaired with different surface treatments and direct composites. Methods: 180 specimens were prepared with Targis, belleGlass HP and Sculpture indirect composites, light-activated and post-cured according to the manufacturers` recommendations. The specimens were stored in distilled water for 24 hours at 37 degrees C. The bonding surfaces were prepared with air abrasion, hydrofluoric acid or hydrofluoric acid followed by a neutralizing solution. All the treated surfaces were subject to the application of a silane and a bonding agent before the repair procedures with Tetric Ceram and Tetric Flow for the Targis specimens, Herculite XRV and Revolution for the belleGlass HP specimens and Sculp-It and Flow-It for Sculpture specimens. The tensile bond strength tests were carried out using a universal testing machine at cross-head speed of 0.5 mm/minute. The type of fracture was observed under a light microscope at x40 magnification. Data were analyzed by a two-way ANOVA and Tukey`s post-hoc tests (P<0.05). Results: Targis showed a statistically higher repair bond strength than belleGlass HP and Sculpture, which were not significantly different from each other. Air abrasion increased the repair bond strength of belleGlass HP and Sculpture. For Targis, all the surface treatments resulted in similar repair bond strength. The different viscosity of repair composites did not affect the repair of indirect composites. Fractured surfaces showed mostly adhesive failures, mainly with hydrofluoric acid treatment.

Bleaching Agents with Varying Concentrations of Carbamide and/or Hydrogen Peroxides: Effect on Dental Microhardness and Roughness

To evaluate the effect of low and highly concentrated bleaching agents on microhardness and surface roughness of bovine enamel and root dentin. According to a randomized complete block design, 100 specimens of each substrate were assigned into five groups to be treated with bleaching agents containing carbamide peroxide (CP) at 10% (CP10); hydrogen peroxide (HP) at 7.5% (HP7.5) or 38% (HP38), or the combination of 18% of HP and 22% of CP (HP18/CP22), for 3 weeks. The control group was left untreated. Specimens were immersed in artificial saliva between bleaching treatments. Knoop surface microhardness (SMH) and average surface roughness (Ra) were measured at baseline and post-bleaching conditions. For enamel, there were differences between bleaching treatments for both SMH and Ra measurements (p = 0.4009 and p = 0.7650, respectively). SMH significantly increased (p < 0.0001), whereas Ra decreased (p = 0.0207) from baseline to post-bleaching condition. For root dentin, the group treated with CP10 exhibited the significantly highest SMH value differing from those groups bleached with HP18/CP22, HP7.5, which did not differ from each other. Application of HP38 resulted in intermediate SMH values. No significant differences were found for Ra (p = 0.5975). Comparing the baseline and post-bleaching conditions, a decrease was observed in SMH (p < 0.0001) and an increase in Ra (p = 0.0063). Bleaching agents with varying concentrations of CP and/or HP are capable of causing mineral loss in root dentin. Enamel does not perform in such bleaching agent-dependent fashion when one considers either hardness or surface roughness evaluations. Bleaching did not alter the enamel microhardness and surface roughness, but in root dentin, microhardness seems to be dependent on the bleaching agent used.

Shear Bond Strength and Ultrastructural Interface Analysis of Different Adhesive Systems to Bleached Dentin

Background: It remains unclear as to whether or not dental bleaching affects the bond strength of dentin/resin restoration. Purpose: To evaluated the bond strength of adhesive systems to dentin submitted to bleaching with 38% hydrogen peroxide (HP) activated by LED-laser and to assess the adhesive/dentin interfaces by means of SEM. Study design: Sixty fragments of dentin (25 mm(2)) were included and divided into two groups: bleached and unbleached. HP was applied for 20 s and photoactivated for 45 s. Groups were subdivided according to the adhesive systems (n = 10): (1) two-steps conventional system (Adper Single Bond), (2) two-steps self-etching system (Clearfil standard error (SE) Bond), and (3) one-step self-etching system (Prompt L-Pop). The specimens received the Z250 resin and, after 24 h, were submitted to the bond strength test. Additional 30 dentin fragments (n = 5) received the same surface treatments and were prepared for SEM. Data were analyzed by ANOVA and Tukey`s test (alpha = 0.05). Results: There was significant strength reduction in bleached group when compared to unbleached group (P < 0.05). Higher bond strength was observed for Prompt. Single Bond and Clearfil presented the smallest values when used in bleached dentin. SEM analysis of the unbleached specimens revealed long tags and uniform hybrid layer for all adhesives. In bleached dentin, Single Bond provided open tubules and with few tags, Clearfil determined the absence of tags and hybrid layer, and Prompt promoted a regular hybrid layer with some tags. Conclusions: Prompt promoted higher shear bond strength, regardless of the bleaching treatment and allowed the formation of a regular and fine hybrid layer with less deep tags, when compared to Single Bond and Clearfil. Microsc. Res. Tech. 74:244-250, 2011. (C) 2010 Wiley-Liss, Inc.

Effect of different bleaching systems on the ultrastructure of bovine dentin

The aim of this study was to evaluate in vitro the effect of different in-office bleaching systems on the surface morphology of bovine dentin. Thirty tooth fragments measuring 4 x 4mm, containing enamel and dentin, were obtained from the crowns of extracted bovine incisors. Samples were subjected to simulated intracoronal bleaching techniques using conventional (Opalescence Endo (R) and Whiteness Super Endo (R)) and light-activated systems (Opalescence Xtra (R) and Whiteness HP Maxx (R)). Controls were treated with either sodium perborate mixed with 10% hydrogen peroxide or no bleaching agent. The samples were observed under SEM and the recorded images were evaluated for topographic alterations. The ultrastructural alterations of dentin observed in this study varied greatly between groups according to the products used. Higher pH products (Whiteness HP Maxx (R) and Opalescence Xtra (R)) associated with in-office techniques yielded better maintenance of dentin ultrastructure. Apparently, both low pH and hydrogen peroxide oxidation play a role in altering the ultrastructure of dentin during internal dental bleaching. The use of alkaline products with reduced time of application (in-office techniques) may decrease such morphological alterations.

Additive genetic relationships between scrotal circumference, heifer pregnancy, and stayability in Nellore cattle

Scrotal circumference data from 47,605 Nellore young bulls, measured at around 18 mo of age (SC18), were analyzed simultaneously with 27,924 heifer pregnancy (HP) and 80,831 stayability (STAY) records to estimate their additive genetic relationships. Additionally, the possibility that economically relevant traits measured directly in females could replace SC18 as a selection criterion was verified. Heifer pregnancy was defined as the observation that a heifer conceived and remained pregnant, which was assessed by rectal palpation at 60 d. Females were exposed to sires for the first time at about 14 mo of age (between 11 and 16 mo). Stayability was defined as whether or not a cow calved every year up to 5 yr of age, when the opportunity to breed was provided. A Bayesian linear-threshold-threshold analysis via Gibbs sampler was used to estimate the variance and covariance components of the multitrait model. Heritability estimates were 0.42 +/- 0.01, 0.53 +/- 0.03, and 0.10 +/- 0.01, for SC18, HP, and STAY, respectively. The genetic correlation estimates were 0.29 +/- 0.05, 0.19 +/- 0.05, and 0.64 +/- 0.07 between SC18 and HP, SC18 and STAY, and HP and STAY, respectively. The residual correlation estimate between HP and STAY was -0.08 +/- 0.03. The heritability values indicate the existence of considerable genetic variance for SC18 and HP traits. However, genetic correlations between SC18 and the female reproductive traits analyzed in the present study can only be considered moderate. The small residual correlation between HP and STAY suggests that environmental effects common to both traits are not major. The large heritability estimate for HP and the high genetic correlation between HP and STAY obtained in the present study confirm that EPD for HP can be used to select bulls for the production of precocious, fertile, and long-lived daughters. Moreover, SC18 could be incorporated in multitrait analysis to improve the prediction accuracy for HP genetic merit of young bulls.