Photodynamic Effects of Curcumin Against Cariogenic Pathogens

Background data: The presence of Streptococcus mutans and Lactobacillus acidophilus in dental structure is an indicator of a cariogenic biofilm. Photodynamic therapy is a technique that involves the activation of photosensitizers by light in the presence of oxygen, resulting in the production of reactive radicals capable of inducing cell death. Reduction of bacteria levels can provide additional means of preventing dental caries. Objective: The present study evaluated the susceptibility of planktonic cultures of S. mutans (ATCC 25175) and L. acidophilus (ATCC-IAL-523) from the Adolfo Lutz Institute (IAL) to photodynamic therapy after sensitization with curcumin and exposure to blue light at 450 nm. Methods: Bacterial suspensions of S. mutans and L. acidophilus isolated (as single species) and combined (multspecies) were prepared and then evaluated. Four different groups were analyzed: L-D- (control group), L-D+ (drug group), L+D- (light group), and L+D+ (photodynamic therapy group). Two different concentrations of curcumin were tested (0.75 and 1.5 g/L) associated with a 5.7 J/cm(2) light emission diode. Results: Significant decreases (p < 0.05) in the viability of S. mutans were only observed when the bacterial suspensions were exposed to both curcumin and light. Then, reductions in viability of up to 99.99% were observed when using 1.5 g/L of the photosensitizer. The susceptibility of L. acidophilus was considerably lower (21% and 37.6%) for both curcumin concentrations. Conclusions: Photodynamic therapy was found to be effective in reducing S. mutans and L. acidophilus on planktonic cultures. No significant reduction was found for L-D+, proving the absence of dark toxicity of the drug.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

Antioxidant defenses and biochemical changes in the neotropical fish pacu, Piaractus mesopotamicus: Responses to single and combined copper and hypercarbia exposure

This study investigated the potentially detrimental effects of copper and elevated aquatic CO2 (hypercarbia), alone or in combination, on pacu, Piaractus mesopotamicus. Fish were exposed for 48 h to control (no copper addition in normocarbia), to 400 mu g Cu2+L-1, to hypercarbic (1% CO2; PCO2=6.9 mm Hg) water and to 400 mu g Cu2+L-1+ hypercarbia. In liver the single factors caused an increase in lipid hydroperoxide concentration that was not observed when the factors were combined. Copper exposure elicited increased hepatic superoxide dismutase activity, irrespective of aquatic CO2 level. On the other hand, the effects of copper on hepatic glutathione peroxidase activity were dependent on water CO2 levels. The two stressors combined did not affect hepatic catalase activity. Hypercarbic water caused a decline in plasma glucose concentration, but this was not observed when hypercarbia was combined with copper exposure. Copper caused a decrease in branchial Na+/K+-ATPase activity that was independent of water CO2 level. Copper caused an increase in branchial metallothionein concentration that was independent of water CO2 level. Thus, branchial metallothionein and Na+/K+-ATPase were effective biomarkers of copper exposure that were not affected by water CO2 level. (C) 2012 Elsevier Inc. All rights reserved.

Effects of Natural Radiation, Photosynthetically Active Radiation and Artificial Ultraviolet Radiation-B on the Chloroplast Organization and Metabolism of Porphyra acanthophora var. brasiliensis (Rhodophyta, Bangiales)

We undertook a study of Porphyra acanthophora var. brasiliensis to determine its responses under ambient conditions, photosynthetically active radiation (PAR), and PAR+UVBR (ultraviolet radiation-B) treatment, focusing on changes in ultrastructure, and cytochemistry. Accordingly, control ambient samples were collected in the field, and two different treatments were performed in the laboratory. Plants were exposed to PAR at 60 mu mol photons m(-2) s(-1) and PAR+UVBR at 0.35 W m(-2) for 3 h per day during 21 days of in vitro cultivation. Confocal laser scanning microscopy analysis of the vegetative cells showed single stellate chloroplast in ambient and PAR samples, but in PAR+UVBR-exposed plants, the chloroplast showed alterations in the number and form of arms. Under PAR+UVBR treatment, the thylakoids of the chloroplasts were disrupted, and an increase in the number of plastoglobuli was observed, in addition to mitochondria, which appeared with irregular, disrupted morphology compared to ambient and PAR samples. After UVBR exposure, the formation of carpospores was also observed. Plants under ambient conditions, as well as those treated with PAR and PAR+UVBR, all showed different concentrations of enzymatic response, including glutathione peroxidase and reductase activity. In summary, the present study demonstrates that P. acanthophora var. brasiliensis shows the activation of distinct mechanisms against natural radiation, PAR and PAR+UVBR.

Serrumab: A human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom

In Brazil, the species Tityus serrulatus is responsible for the most severe cases of scorpion envenomation. There is currently a need for new scorpion anti-venoms that are more effective and less harmful. This study attempted to produce human monoclonal antibodies capable of inhibiting the activity of T. serrulatus venom (TsV), using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Four rounds of phage antibody selection were performed, and the round with the highest phage antibody titer was chosen for the production of monoclonal phage antibodies and for further analysis. The scFv 2A, designated serrumab, was selected for the production and purification of soluble antibody fragments. In a murine peritoneal macrophage cell line (J774.1), in vitro assays of the cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-10 were performed. In male BALB/c mice, in vivo assays of plasma urea, creatinine, aspartate transaminase, and glucose were performed, as well as of neutrophil recruitment and leukocyte counts. It was found that serrumab inhibited the TsV-induced increases in the production of IL-6, TNF alpha, and IL-10 in J774.1 cells. The in vivo inhibition assay showed that serrumab also prevented TsV-induced increases in the plasma levels of urea, creatinine, aspartate transaminase, and glucose, as well as preventing the TsV-induced increase in neutrophil recruitment. The results indicate that the human monoclonal antibody serrumab is a candidate for inclusion in a mixture of specific antibodies to the various toxins present in TsV. Therefore, serrumab shows promise for use in the production of new anti-venom.

Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin - than on footpad-infected mice

Lesion development in tegumentary leishmaniasis is markedly influenced by the inoculation site and the type and number of injected infective forms. This and the yet unclear contribution of Th2 cytokines as susceptibility factors to Leishmania amazonensis infection prompted us to investigate the roles of IL-4, IL-13 and IL-10 on C57BL/6 and BALB/c mice infected in the footpad (paw) or rump with low-dose L. amazonensis purified-metacyclics. Wild-type (WT) mice of either strain developed, in the rump, a single large ulcerated lesion whereas paw lesions never ulcerated and were much smaller in C57BL/6 than in BALB/c mice. However, rump-inoculated IL-4-deficient (IL-4(-/-))C57BL/6 mice did not develop any visible lesions although parasites remained in the dermis and lymph nodes, even after systemic IL-10-receptor blocking. By comparison, all IL-4(-/-) BALB/c mice developed rump ulcers. Strikingly, only 30% of rump-infected IL-4R alpha(-/-) BALB/c mice developed lesions. IL-4(-/-) mice had higher IFN-gamma and lower IL-10 and IL-13 levels than WT mice. Paw-infected IL-4R alpha(-/-) BALB/c mice developed minimal paw lesions. While other factors contributing to L amazonensis susceptibility cannot be discounted, our results indicate that absent signalling by IL-4 or by IL-4/IL-13 have more intense attenuating effects on rump than on paw lesions but do not eradicate parasitism. (C) 2011 Elsevier Inc. All rights reserved.

Effect of a single session of aerobic walking exercise on arterial pressure in community-living elderly individuals

Several studies have demonstrated that one exercise session (ES) on a cycloergometer or ergometric treadmill causes a reduction in blood pressure (BP). However, there are few similar studies on walking, which is the exercise modality most available to the elderly. We investigated the immediate and 24-h effects of walking on BP in independent, community-living elderly individuals. Volunteers participated in a single ES and resting control session (CS). Before and after each session, BP was measured by auscultatory and oscillometric methods. After each session, 24-h ambulatory blood pressure monitoring was conducted. An accelerometer was installed 48 h before the sessions and left in place for 5 days. The mean volunteer age was 67.7 +/- 3.5 years; 11 were hypertensive patients under treatment, and 12 were normotensive. In the total sample, there were immediate 14mm Hg and 12 mm Hg reductions in systolic BP (SBP) after the ES according to the auscultatory and oscillometric methods, respectively. Diastolic BP (DBP) was reduced by 4 mm Hg after the ES according to both methods. SBP during wakefulness and sleep and DBP during wakefulness were lower after the ES than after the CS (P<0.01), when wakefulness and sleep were determined individually (variable-time pattern) using data from the activity monitors and provided by the volunteers. The variable-time pattern was more effective in detecting reductions in BP than the fixed-time pattern. Hypertension Research (2012) 35, 457-462; doi: 10.1038/hr.2011.227; published online 9 February 2012

Anisotropic Flow in Event-by-Event Ideal Hydrodynamic Simulations of root s(NN) 200 GeV Au+Au Collisions

We simulate top-energy Au + Au collisions using ideal hydrodynamics in order to make the first comparison to the complete set of midrapidity flow measurements made by the PHENIX Collaboration. A simultaneous calculation of nu(2), nu(3), nu(4), and the first event-by-event calculation of quadrangular flow defined with respect to the nu(2) event plane (nu(4){Psi(2)}) gives good agreement with measured values, including the dependence on both transverse momentum and centrality. This provides confirmation that the collision system is indeed well described as a quark-gluon plasma with an extremely small viscosity and that correlations are dominantly generated from collective effects. In addition, we present a prediction for nu(5).

Dynamic symmetry loss of high-frequency hysteresis loops in single-domain particles with uniaxial anisotropy

Understanding how magnetic materials respond to rapidly varying magnetic fields, as in dynamic hysteresis loops, constitutes a complex and physically interesting problem. But in order to accomplish a thorough investigation, one must necessarily consider the effects of thermal fluctuations. Albeit being present in all real systems, these are seldom included in numerical studies. The notable exceptions are the Ising systems, which have been extensively studied in the past, but describe only one of the many mechanisms of magnetization reversal known to occur. In this paper we employ the Stochastic Landau-Lifshitz formalism to study high-frequency hysteresis loops of single-domain particles with uniaxial anisotropy at an arbitrary temperature. We show that in certain conditions the magnetic response may become predominantly out-of-phase and the loops may undergo a dynamic symmetry loss. This is found to be a direct consequence of the competing responses due to the thermal fluctuations and the gyroscopic motion of the magnetization. We have also found the magnetic behavior to be exceedingly sensitive to temperature variations, not only within the superparamagnetic-ferromagnetic transition range usually considered, but specially at even lower temperatures, where the bulk of interesting phenomena is seen to take place. (C) 2011 Elsevier B.V. All rights reserved.

Effects of Hepatocyte Growth Factor Injection and Reinjection on Healing in the Rabbit Vocal Fold

Objectives/Hypothesis. Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays various roles in embryogenesis and tissue regeneration and exhibits marked antifibrotic activity. The present study sought to assess the effects of HGF injection and reinjection coinciding with its peak of activity on collagen density, vessel density, inflammatory reaction in the lamina propria, and mean epithelial thickness in the injured rabbit vocal fold. Study Design. Prospective, controlled, experimental animal study. Methods. Fourteen rabbits were subdivided into two groups and underwent injury of the vocal folds. Immediately after injury, animals in group 1 received HGF injections into the right vocal fold (RVF), whereas those in group 2 received bilateral HGF injections and a single reinjection into the RVF 10 days after the first, to coincide with the peak of HGF activity. The left vocal folds (LVFs) served as controls in both groups. Histological assessment of laryngeal specimens was performed at 30 and 40 days, respectively. Results. In both groups, collagen density was lower in the right (treated) vocal folds than in the left (control) folds (P = 0.018). Vessel density was higher in the RVFs in group 2 (P = 0.018). Differences were found in mean epithelial thickness and inflammatory reaction in the lamina propria but did not reach statistical significance. Conclusions. In the scarred rabbit vocal fold, HGF injection is associated with decreased collagen density in the lamina propria, whereas reinjection after 10 days produces decreased collagen density and higher vessel density.

Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan (R) PCR. APOE epsilon 2/epsilon 3/epsilon 4 genotyping was performed using PCR-RFLP. Total cholesterol (TC). LDL-c and apoB were reduced after each treatment (p<0.001). Triglycerides, VLDL-c and apoAl were reduced only after atorvastatin (p<0.05), whereas triglycerides and VLDL-c were increased after HT (p=0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT+AT groups (p<0.05). APOE mRNA expression was reduced after atorvastatin treatment (p=0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms, however the reduction on APOE expression was more pronounced in epsilon 3 epsilon 3 than in epsilon 3 epsilon 4 carriers. Atorvastatin down-regulates APOE mRNA expression and it is modified by APOE genotypes in PBMC from postmenopausal women. (C) 2011 Elsevier Ltd. All rights reserved.

Geochemical evidence of the 8.2 ka event and other Holocene environmental changes recorded in paleolagoon sediments, southeastern Brazil

The paleoclimatic record of Jureia Paleolagoon, coastal southeastem Brazil, includes cyclic and gradual changes with different intensities and frequencies through geological time, and it is controlled by astronomical, geophysical, and geological phenomena. These variations are not due to one single cause, but they result from the interaction of several factors, which act at different temporal and spatial scales. Here, we describe paleoenvironmental evidence regarding climatic and sea level changes from the last 9400 cal yr BP at the Jureia Paleolagoon - one of the main groups of protected South Atlantic ecosystems. Geochemical evidences were used to identify anomalies from multi-proxy analyses of a paleolagoon sediment core. The anomalies of centennial scale were correlated to climate and transgression-regression cycles from the Holocene period. Decadal scale anomalous oscillations in the Quaternary paleolagoon sediments occur between 9400 and 7500 cal yr BP, correlated with long- and short-term natural events, which generated high sedimentation rates, mainly between 8385 and 8375 cal yr BP (10 cm/yr). Our results suggest that a modem-day short-duration North Atlantic climatic event, such as the 82 ka event, could affect the environmental equilibrium in South America and intensify the South American Summer Monsoon. (C) 2011 University of Washington. Published by Elsevier Inc. All rights reserved.

Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.

The immediate effects of local and adjacent acupuncture on the tibialis anterior muscle: a human study

Abstract Background This study compares the immediate effects of local and adjacent acupuncture on the tibialis anterior muscle and the amount of force generated or strength in Kilogram Force (KGF) evaluated by a surface electromyography. Methods The study consisted of a single blinded trial of 30 subjects assigned to two groups: local acupoint (ST36) and adjacent acupoint (SP9). Bipolar surface electrodes were placed on the tibialis anterior muscle, while a force transducer was attached to the foot of the subject and to the floor. An electromyograph (EMG) connected to a computer registered the KGF and root mean square (RMS) before and after acupuncture at maximum isometric contraction. The RMS values and surface electrodes were analyzed with Student's t-test. Results Thirty subjects were selected from a total of 56 volunteers according to specific inclusion and exclusion criteria and were assigned to one of the two groups for acupuncture. A significant decrease in the RMS values was observed in both ST36 (t = -3.80, P = 0,001) and SP9 (t = 6.24, P = 0.001) groups after acupuncture. There was a decrease in force in the ST36 group after acupuncture (t = -2.98, P = 0.006). The RMS values did not have a significant difference (t = 0.36, P = 0.71); however, there was a significant decrease in strength after acupuncture in the ST36 group compared to the SP9 group (t = 2.51, P = 0.01). No adverse events were found. Conclusion Acupuncture at the local acupoint ST36 or adjacent acupoints SP9 reduced the tibialis anterior electromyography muscle activity. However, acupuncture at SP9 did not decrease muscle strength while acupuncture at ST36 did.

Effects of pretreatment on morphology, chemical composition and enzymatic digestibility of eucalyptus bark: a potentially valuable source of fermentable sugars for biofuel production – part 1

Abstract Background In recent years, the growing demand for biofuels has encouraged the search for different sources of underutilized lignocellulosic feedstocks that are available in sufficient abundance to be used for sustainable biofuel production. Much attention has been focused on biomass from grass. However, large amounts of timber residues such as eucalyptus bark are available and represent a potential source for conversion to bioethanol. In the present paper, we investigate the effects of a delignification process with increasing sodium hydroxide concentrations, preceded or not by diluted acid, on the bark of two eucalyptus clones: Eucalyptus grandis (EG) and the hybrid, E. grandis x urophylla (HGU). The enzymatic digestibility and total cellulose conversion were measured, along with the effect on the composition of the solid and the liquor fractions. Barks were also assessed using Fourier-transform infrared spectroscopy (FTIR), solid-state nuclear magnetic resonance (NMR), X-Ray diffraction, and scanning electron microscopy (SEM). Results Compositional analysis revealed an increase in the cellulose content, reaching around 81% and 76% of glucose for HGU and EG, respectively, using a two-step treatment with HCl 1%, followed by 4% NaOH. Lignin removal was 84% (HGU) and 79% (EG), while the hemicellulose removal was 95% and 97% for HGU and EG, respectively. However, when we applied a one-step treatment, with 4% NaOH, higher hydrolysis efficiencies were found after 48 h for both clones, reaching almost 100% for HGU and 80% for EG, in spite of the lower lignin and hemicellulose removal. Total cellulose conversion increased from 5% and 7% to around 65% for HGU and 59% for EG. NMR and FTIR provided important insight into the lignin and hemicellulose removal and SEM studies shed light on the cell-wall unstructuring after pretreatment and lignin migration and precipitation on the fibers surface, which explain the different hydrolysis rates found for the clones. Conclusion Our results show that the single step alkaline pretreatment improves the enzymatic digestibility of Eucalyptus bark. Furthermore, the chemical and physical methods combined in this study provide a better comprehension of the pretreatment effects on cell-wall and the factors that influence enzymatic digestibility of this forest residue.