Study of an alternative phosphate sealer for replacement of hexavalent chromium

This study evaluates the possibility of replacing the hexavalent chromium passivation treatment used as a sealer after phosphating of carbon steel (SAE 1010) by a treatment with niobium ammonium oxalate (Ox). Samples of carbon steel (SAE 1010) after being phosphated in a zinc phosphate bath (PZn + Ni) were immersed in solution of niobium ammonium oxalate (250 mg L(-1) of Nb) either at pH 3.0 or pH 8.0. A passivation treatment with a solution with CrO(3) (200 mg L(-1) of Cr(6+)) was also used for reference. The corrosion resistance of the phosphated samples after passivation treatments was analyzed in a NaCl 0.5 mol L(-1) solution using electrochemical impedance spectroscopy (EIS) and anodic polarization curves. Salt spray tests were also performed to evaluate their corrosion resistance. The results showed that the highest corrosion resistance was obtained by passivation in a solution with (250 mg L(-1) of Nb) at pH 8.0. (C) 2010 Elsevier B.V. All rights reserved.

Correlation Between Autofluorescence Intensity and Tumor Area in Mice Bearing Renal Cell Carcinoma

Protoporphyrin IX (PpIX) is a porphyrin derivative that is accumulated in cancerous tissue in consequence of the tumor-specific metabolic alterations. The aim of this study was to evaluate the accumulation of PpIX in mice bearing renal cell carcinoma by spectroscopy analysis. A total of 24 male Balb/c mice, 6 weeks old, were divided into six groups: Normal (without inoculation of tumor cells) and 4, 8, 13, 16, and 20 days after inoculation of tumor cells. The orthotopic tumor model of renal cancer was used. Murine renal cell carcinoma (Renca cells) were inoculated into the subcapsular space of the kidney. Normal and tumor-bearing kidneys in different progression stages were removed and analyzed by ex-vivo spectroscopy and by microscopy, for tumor histometric analysis. Emission spectra were obtained by exciting the samples at 405 nm. Significant differences between normal and tumor-bearing kidneys in autofluorescence shape occurred in the 600-700 nm spectral region. A good correlation was found between emission band intensity at 635 nm and the tumor area.

Normal Doppler velocimetry of renal vasculature in Persian cats

Renal diseases are common in older cats. Decreased renal blood flow may be the first sign of dysfunction and can be evaluated by Doppler ultrasound. But previous studies suggest that the resistive index (RI) has a low sensitivity for detecting renal disease. Doppler waveforms of renal and intrarenal arteries demonstrate decreased blood flow before there are any changes in the RI. The purpose of this study was to evaluate the normal Doppler flowmetrics parameters of renal arteries (RAs), interlobar arteries (IAs) and abdominal aorta (AO) in adult healthy, Persian cats. Twenty-five Persian cats (13 females and 12 males with mean age of 30 months and an age range 12-60 months) with normal clinical examinations and biochemical tests and normal systemic blood pressure were given B-mode ultrasonographies in order to exclude all nephropathies, including polycystic kidney disease. All measurements were performed on both kidneys. Both kidneys (n = 50) were examined by color mapping of the renal vasculature. Pulsed Doppler was used to examine both RAs, the IAs at cranial, middle and caudal sites, and the AO. The RI was calculated for all of the vessels. Early systolic acceleration (ESA) of RA and IA was obtained with Doppler spectral analysis. Furthermore, the ratio indices between RA/AO, and IA/RA velocities were calculated. The mean values of peak systolic velocity (PSV) and the diameter for AO were 53.17 +/- 13.46 cm/s and 0.38 +/- 0.08 cm, respectively. The mean RA diameter for all 50 kidneys was 0.15 +/- 0.02 cm. Considering the velocimetric values in both RAs, the mean PSV and RI that were obtained were 41.17 +/- 9.40 cm/s and 0.54 +/- 0.07. The RA had a mean ESA of 1.12 +/- 1.14 m/s(2) and the calculated upper limit of the reference value was 3.40 m/s(2). The mean renal-aortic ratio was 0.828 +/- 0.296. The IA showed PSV and RI values of 32.16 +/- 9.33 cm/s and 0.52 +/- 0.06, respectively. The mean ESA of all IAs was 0.73 +/- 0.61 m/s(2). The calculated upper limit of the reference value was 2.0 m/s(2). The mean renal-interlobar artery ratio was 1.45 +/- 0.57. The RI values obtained in this study were similar to values reported in the literature. Some conditions that lead to a decrease in compliance and to an increase in vascular resistance can affect the Doppler spectral waveforms without changes in RI. To our knowledge, there are no studies that were directed toward to the normal ESA values of the renal vasculature in Persian cats. This study introduced a new ratio between the PSV of the RA and the IA. This index was developed based on the well-known effects of Doppler on the detection of stenosis, regardless of the cause. Further studies are necessary to verify the hemodynamic behavior of this index under pathological conditions in cats as well as the effect of aging, nephropathies and systemic pressure on Doppler velocimetric parameters. (C) 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Effects of refrigeration, freezing and replacement of milk fat by inulin and whey protein concentrate on texture profile and sensory acceptance of synbiotic guava mousses

The effects of refrigeration, freezing and substitution of milk fat by inulin and whey protein concentrate (WPC) on the texture and sensory features of synbiotic guava mousses supplemented with the probiotic, Lactobacillus acidophilus La-5, and the prebiotic fibre oligofructose, were studied. The frozen storage (-18 +/- 1 degrees C), followed by thawing at 4 degrees C before the analyses, and the complete replacement of the milk fat by inulin plus WPC, led to significant differences in the instrumental texture parameters of mousses (P < 0.05). Nonetheless, these changes did not affect the sensory acceptability of the products studied. The frozen storage may be employed to extend the shelf-life of synbiotic guava mousses. Additionally, to obtain a texture profile similar to the traditional product, the simultaneous addition of inulin and WPC is recommended only for the partial replacement of milk fat in refrigerated and frozen mousses, and the total proportion of both ingredients together should not exceed 2.6%. (C) 2010 Elsevier Ltd. All rights reserved.

Timing and Dose of Statin Therapy Define Its Impact on Inflammatory and Endothelial Responses During Myocardial Infarction

Objective-Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. Methods and Results-ST-elevation MI patients (n = 125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0 +/- 4.1 mg/L) and patients treated with 20 (8.5 +/- 4.0 mg/L), 40 (3.8 +/- 2.5 mg/L), and 80 mg/day (1.4 +/- 1.5 mg/L), and the daily differences remained significant until the seventh day (P < 0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-alpha, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P < 0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-alpha, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P < 0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P = 0.001). Conclusion-This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit.

Alpha-tocopherol supplementation decreases electronegative low-density lipoprotein concentration [LDL(-)] in haemodialysis patients

Background. Oxidative stress is a significant contributor to cardiovascular diseases (CVD) in haemodialysis (HD) patients, predisposing to the generation of oxidized low-density lipoprotein (oxLDL) or electronegatively charged LDL subfraction. Antioxidant therapy such as alpha-tocopherol acts as a scavenger of lipid peroxyl radicals attenuating the oxidative stress, which decreases the formation of oxLDL. The present study was designed to investigate the influence of the alpha-tocopherol supplementation on the concentration of electronegative low-density lipoprotein [LDL(-)], a minimally oxidized LDL, which we have previously described to be high in HD patients. Methods. Blood samples were collected before and after 120 days of supplementation by alpha-tocopherol (400 UI/day) in 19 stable HD patients (50 +/- 7.8 years; 9 males). The concentrations of LDL(-) in blood plasma [using an anti-LDL- human monoclonal antibody (mAb)] and the anti-LDL(-) IgG auto-antibodies were determined by ELISA. Calculation of body mass index (BMI) and measurements of waist circumference (WC), triceps skin folds (TSF) and arm muscle area (AMA) were performed. Results. The plasma alpha-tocopherol levels increased from 7.9 mu M (0.32-18.4) to 14.2 mu M (1.22-23.8) after the supplementation (P = 0.02). The mean concentration of LDL(-) was reduced from 570.9 mu g/mL (225.6-1241.0) to 169.1 mu g/mL (63.6-621.1) (P < 0.001). The anti-LDL(-) IgG auto-antibodies did not change significantly after the supplementation. The alpha-tocopherol supplementation also reduced the total cholesterol and LDL-C levels in these patients, from 176 +/- 42.3 mg/dL to 120 +/- 35.7 mg/dL (P < 0.05) and 115.5 +/- 21.4 mg/dL to 98.5 +/- 23.01 mg/dL (P < 0.001), respectively. Conclusion. The oral administration of alpha-tocopherol in HD patients resulted in a significant decrease in the LDL(-), total cholesterol and LDL-C levels. This effect may favour a reduction in cardiovascular risk in these patients, but a larger study is required to confirm an effect in this clinical setting.

Manufacture of low-sodium Minas fresh cheese: Effect of the partial replacement of sodium chloride with potassium chloride

We investigated the effect of sodium reduction by partial substitution of sodium chloride (NaCl) with potassium chloride (KCl) on the manufacture of Minas fresh cheese during 21 d of refrigerated storage. Four treatments of low-sodium Minas fresh cheese were manufactured, with partial replacement of NaCl by KCl at 0, 25, 50, and 75% (wt/wt), respectively. The cheeses showed differences in the content of moisture, ash, protein, salt, and lipid contents, as well as on the extent of proteolysis and hardness throughout the storage period. However, no difference was observed among treatments within each storage day tested. The partial substitution of NaCl by KCl decreased up to 51.8% the sodium concentration of the cheeses produced. The consumer test indicated that it is possible to manufacture a low-sodium Minas fresh cheese that is acceptable to consumers by partial substitution of NaCl by KCl at 25% (wt/wt) in the salting step.

Photoinduced Nitric Oxide and Singlet Oxygen Release from ZnPC Liposome Vehicle Associated with the Nitrosyl Ruthenium Complex: Synergistic Effects in Photodynamic Therapy Application

Under continuous photolysis at 675 nm, liposomal zinc phthalocyanine associated with nitrosyl ruthenium complex [Ru(NH.NHq)(tpy)NO](3+) showed the detection and quantification of nitric oxide (NO) and singlet oxygen ((1)O(2)) release. Photophysical and photochemical results demonstrated that the interaction between the nitrosyl ruthenium complex and the photosensitizer can enable an electron transfer process from the photosensitizer to the nitrosyl ruthenium complex which leads to NO release. Synergistic action of both photosensitizers and the nitrosyl ruthenium complex results in the production of reactive oxygen species and reactive nitrogen species, which is a potent oxidizing agent to many biological tissues, in particular neoplastic cells.

Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats

We have described a new compound (trans-[RuCl([15]ane N(4))NO](2+)), which in vitro releases NO by the action of a reducing agent such as catecholamines. We investigated the effect of this NO donor in lowering the mean arterial pressure (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured before and after intravenous in bolus injection of the compound in conscious 2K-1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70 +/- 8.70 mmHg, n=5), the MAP was reduced in -34.25 +/- 13.50 mmHg(P < 0.05) 6 h after administration of 10 mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no effect. We have also studied the effect of the injection of 0.1 mmol/L/Kg in normotensive (basal 118.20 +/- 11.25 mmHg, n = 4), moderate (basal 160.90 +/- 2.30 mmHg, n = 6), and severe hypertensive rats (basal 202.46 +/- 16.74 mmHg, n = 6). The compound at the dose of 0.1 mmol/L/Kg did not have effect (P> 0.05) on MAP of normotensive and moderate hypertensive rats. However, in the severe hypertensive rats (basal 202.46 +/- 16.70 mmHg, n = 6) there was a significant reduction on the MAP of -28.64 +/- 12.45 mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10 mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1 mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1 mmol/LKg that produced the maximum relaxation. (C) 2008 Elsevier Inc. All rights reserved.

Molecular dynamics, density functional, ADMET predictions, virtual screening, and molecular interaction field studies for identification and evaluation of novel potential CDK2 inhibitors in cancer therapy

In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter. One of the proposals and one of the drug-like compounds selected by virtual screening indicated to be promising candidates for CDK2-based cancer therapy.

Photophysical studies and in vitro skin permeation/retention of Foscan (R)/nanoemulsion (NE) applicable to photodynamic therapy skin cancer treatment.

In this work we evaluated the photophysical and in vitro properties of Foscan (R), a second-generation photosensitizer drug (PS) widely used in systemic clinical protocols for cancer therapy based on Photodynamic Therapy (PDT). We employed biodegradable nanoemulsions (NE) as a colloidal vehicle of the oil/water (o/w) type focusing in topical administration of Foscan (R) and other photosensitizer drugs. This formulation was obtained and stabilized by the methodology described by Tabosa do Egito et al.,(30) based on the mixture of two phases: an aqueous solution and an organic medium consisting of nonionic surfactants and oil. The photodynamic potential of the drug incorporated into the NE was studied by steady-state and time-resolved spectroscopic techniques. We also analyzed the in vitro biological behavior carried out in mimetic biological environment protocols based on the animal model. After topical application in a skin animal model, we evaluated the Foscan (R)/NE diffusion flux into the skin layers (stratum corneum and epidermis + dermis) by classical procedures using Franz Diffusion cells. Our results showed that the photophysical properties of PS were maintained after its incorporation into the NE when compared with homogeneous organic medium. The in vitro assays enabled the determination of an adequate profile for the interaction of this system in the different skin layers, with an ideal time lag of 6 h after topical administration in the skin model. The Foscan (R) diffusion flux (J) was increased when this PS was incorporated into the NE, if compared with its flux in physiological medium. These parameters demonstrated that the NE can be potentially applied as a drug delivery system (DDS) for Foscan (R) in both in vitro and in vivo assays, as well as in future clinical applications involving topical skin cancer PDT.

The influence of positive or negative charges in the passive and iontophoretic skin penetration of porphyrins used in photodynamic therapy

Meso-tetra-(N-methylpiridinium-4-yl)-porphyrin (TMPyP) and meso-tetra-(4-sulfonatophenyl)-porphyrin (TPPS(4)) are photosensitizing drugs (PS) used in photodynamic therapy (PDT). Based on the fact that these compounds present similar chemical structures but opposite charges at pH levels near physiological conditions, this work aims to evaluate the in vitro and in vivo influence of these electrical charges on the iontophoretic delivery of TMPyP and TPPS4, attempting to achieve maximum accumulation of PS in skin tissue. The iontophoretic transport of these drugs from a hydrophilic gel was investigated in vitro using porcine ear skin and vertical, flow-through diffusion cells. In vivo experiments using rats were also carried out, and the penetration of the PSs was analyzed by fluorescence microscopy to visualize the manner of how these compounds were distributed in the skin after a short period of iontophoresis application. In vitro, both passive and iontophoretic delivery of the positively charged TMPyP were much greater (20-fold and 67-fold, respectively) than those of the negatively charged TPPS(4). TPPS(4) iontophoresis in vivo increased the fluorescence of the skin only in the very superficial layers. On the other hand, iontophoresis of the positively charged drug expressively increased the rat epidermis and dermis fluorescence, indicating high amounts of this drug throughout the skin layers. Moreover, TMPyP was homogeneously distributed around and into the nuclei of the skin cells, suggesting its potential use in topical PDT. (C) 2010 Elsevier B.V. All rights reserved.

Renal toxicity caused by oral use of medicinal plants: The yacon example

Aim of the study: Yacon [Smallanthus sonchifolius (Poepp. 82 Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs). Materials and methods: The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. Results: The PE was rich in CGAs, but we did not detect any STLs. The AE and LEE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10,50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys. Conclusions: The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic compounds in the leaves of the yacon. Based on our results, we do not recommend the oral use of yacon leaves to treat diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Circulating Interleukin-6 and High-Sensitivity C-Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects

Background: Periodontal disease has been associated with many chronic inflammatory systemic diseases, and a common chronic inflammation pathway has been suggested for these conditions. However, few studies have evaluated whether periodontal disease, in the absence of other known inflammatory conditions and smoking, affects circulating markers of chronic inflammation. This study compared chronic inflammation markers in control individuals and patients with periodontal disease and observed whether non-surgical periodontal therapy affected inflammatory disease markers after 3 months. Methods: Plasma and serum of 20 controls and 25 patients with periodontal disease were obtained prior to and 3 months after non-surgical periodontal therapy. All patients were non-smokers, they did not use any medication, and they had no history or detectable signs and symptoms of systemic diseases. Periodontal and systemic parameters included probing depth, bleeding on probing, clinical attachment level, hematologic parameters, as well as the following inflammatory markers: interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), CD40 ligand, monocyte chemoattractant protein (MCP)-1, soluble P-selectin (sP-selectin), soluble vascular adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. Results: There were no differences in the hematologic parameters of the patients in the control and periodontal disease groups. Among the tested inflammatory markers, IL-6 concentrations were higher in the periodontal disease group at baseline compared to the controls (P=0.006). Therapy was highly effective (P<0.001 for all the analyzed clinical parameters), and a decrease in circulating IL-6 and hs-CRP concentrations was observed 3 months after therapy (P=0.001 and P=0.006, respectively). Our results also suggest that the CD40 ligand marker may have been different in the control and periodontal disease groups prior to the therapy (P=0.009). Conclusions: In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and hs-CRP, which decreased 3 months after non-surgical periodontal therapy. With regard to the CD40 ligand, MCP-1, sP-selectin, sVCAM-1, and sICAM-1, no changes were seen in the periodontal disease group between baseline and 3 months after therapy. J Periodontol 2009;80:594-602.