A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

Desensitization of thermal hyperemia in the skin is reproducible.

OBJECTIVE: Local heating increases skin blood flow SkBF (thermal hyperemia). In a previous study, we reported that a first local thermal stimulus could attenuate the hyperemic response to a second one applied later on the same skin spot, a phenomenon that we termed desensitization. However, other studies found no evidence for desensitization in similar conditions. The aim of the present work was to test whether it was related to differences in instrumentation. METHODS: Twenty-eight healthy young males were studied. Two pairs of heating chambers, one custom-made (our study) and one commercial (other groups), were affixed to forearm skin. SkBF was measured with single-point laser-Doppler flowmetry (LDF) (780nm) in one pair, and laser-Doppler imaging (LDI) (633nm) in the other. A temperature step from 34 to 41°C, was applied for 30minutes and repeated after two hours. RESULTS: During the second thermal challenge, the plateau SkBF was lower than during the first thermal and was observed with each of the four combinations of SkBF measurement techniques and heating equipment (p<0.05 for all conditions, range -9% to -16% of the initial value). CONCLUSION: Desensitization of thermal hyperemia is not specific to peculiar operating conditions.

Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.

OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. CONCLUSION: The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.

Recovery pattern of brachiopods after the Permian-Triassic crisis in South China

In South China, the Changhsingian brachiopods are extraordinarily abundant and diverse, comprising 468 species in 144 genera. However, approximately 91% of brachiopod species were eliminated during the Permian-Triassic (P-Tr) mass extinction event. Brachiopods in the aftermath of the P-Tr mass extinction were extremely rare, with only one opportunistic taxon, Lingulida, occasionally found in the Griesbachian and Smithian at a high abundance. Species-diversity of articulated brachiopods in the early Griesbachian, late Griesbachian, Dienerian, and Smithian are 35, 3, 2, and 0, respectively. Although a few of Mesozoic-type species occurred in the Griesbachian, Dienerian and Smithian, a marked diversification of brachiopods occurred in the Spathian and early Anisian and was characterised by 9 and 17 Mesozoic-type species, respectively. The diversification of brachiopods in the Spathian and early Anisian coincides with the contemporaneous expansion of the refuge zone, suggesting that the improvement of marine environmental conditions (e.g., lethally hot temperature and anoxic seawater) played a key role in brachiopod recovery after the P-Tr mass extinction.

Dietas de baixa proteína no desempenho de frangos criados em diferentes temperaturas

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

Efeito da temperatura ambiente e da idade do frango sobre o valor energético do farelo de soja

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

Empenamento, níveis hormonais de triiodotironina e tiroxina e temperatura corporal de frangos de corte de diferentes genótipos criados em diferentes condições de temperatura

Estudou-se o empenamento, os níveis hormonais de Triiodotironina (T3) e Tiroxina (T4) e a temperatura corporal de frangos criados em diferentes temperaturas. Foram alojados 180 pintainhos Cobb 500 e 180 pintainhos ISA Label JA57, em temperaturas termoneutra, quente ou fria. O delineamento utilizado foi inteiramente ao acaso, em modelo fatorial 2 x 3 (2 linhagens e 3 temperaturas) com 8 repetições. Houve um aumento das concentrações de T3, nas aves criadas no frio, e uma redução no calor. Também no calor, os frangos ISA Label apresentaram níveis mais altos de T4. As aves Cobb apresentaram uma redução de T4 no calor ou no frio aos 42 dias e no calor aos 21 dias de idade. Houve menor empenamento aos 42 dias, quando os frangos foram criados em alta temperatura e um menor empenamento das aves ISA Label, quando comparadas aos frangos Cobb. As aves criadas no calor apresentaram maior temperatura corporal. Os frangos Cobb apresentaram um aumento na sua temperatura interna, quando criados em ambiente quente. Já os frangos da linhagem ISA Label mantiveram sua temperatura interna, independentemente da temperatura ambiente. É possível concluir que a temperatura ambiente afeta o empenamento dos frangos de corte de linhagens de rápido ganho de peso, que também apresentaram menor tolerância ao calor, demonstrada através de uma maior temperatura corporal e temperatura interna.

Thermal degradation of geomembranes after exposure to heat

HDPE and PVC geomembranes are sensitive to changes in their properties when in contact with high temperatures. The effects of hot temperature on polymeric geomembranes are assessed by the ASTM D794 and ASTM D5721.This paper brings an analysis of degradation of the Poly Vinyl Chloride (PVC) and High Density Poly Ethylene (HDPE) geomembranes when exposed to conventional and air oven after specific periods.. Mechanical and physical properties were evaluated. OIT tests were also performanced to evaluate the level of oxidation degradation occurred on the HDPE geomembranes. Geomembranes of two thicknesses were tested: 1.0, 2.0 nun (PVC) and 0.8, 2.5 mm, (HDPE). The results obtained show, for example, that after the last period of exposure, the PVC geomembranes (1.0, 2.0 mm) were more rigid and stiffer than fresh samples. The HDPE geomembranes, on the other hand, when exposed to heat presented increases in deformation. OIT tests showed efficient to detect some level of degradation on the HDPE geomembranes.

Influence of storage period and effect of different brands of acrylic resin on the dimensional accuracy of the maxillary denture base

The aim of this study was to evaluate the dimensional changes of denture bases made from different resins after different storage periods. For this purpose, 25 sets of plaster models/resin bases were prepared using 4 acrylic resins submitted to two types of polymerization: 1- QC-20 submitted to polymerization by microwave energy; 2- QC-20 submitted to polymerization by water hot bath; 3- Vipi Cril submitted to polymerization by water hot bath; 4- Vipi Wave submitted to polymerization by microwave energy; and 5- Onda Cryl submitted to polymerization by microwave energy. After polymerization, the specimens were sectioned for accuracy readings using a comparison microscope. Readings were taken at 3 points: the crests of the right (A) and left (B) ridges, and the median region of the palate, in 4 different periods. The data obtained were submitted to two-way ANOVA and Tukey's test at 5% significance level. The greatest distortions were found in the posterior palatal region of the base (M), with statistically significant difference (p<0.05) for the studied resins. All acrylic resins presented dimensional changes and the storage period influenced these alterations.

Evaluation of hardness and color stability in the soft lining materials after thermocycling and chemical polishing.

The aim of this study was to evaluate the Shore A hardness and color stability of two soft lining materials after thermocycling and when chemical polishing was used or omitted. Two acrylic-based soft lining materials were tested: Coe-Soft and Soft Confort, 14 specimens were made for each material. They were distributed in four groups according to the treatment performed. The specimens were thermocycled (1000 cycles) and half of the group submitted to chemical polishing (methyl methacrylate). Shore A hardness was determined and color stability was calculated by means of Commission International de l'Eclairage Lab uniform color scale using a spectrophotometer, the measurements were made immediately after deflasked, chemical polishing and thermocycling. Analysis of variance (ANOVA) and Tukey's tests were performed at p < 0.01. Color changes (deltaE) were observed after thermocycling in both soft lining materials: Soft Confort (10.60) showed significantly higher values than Coe-Soft (4.57). Coe-Soft (26.42) showed higher Shore A hardness values than Soft Confort (19.42). Chemical polishing did not influence in the color stability of both materials; however, influenced in the hardness values of Coe-Soft.

Effect of sodium bicarbonate on Candida albicans adherence to thermally activated acrylic resin

The purpose of this study was to evaluate the effect of 5% sodium bicarbonate on the adherence of Candida albicans to thermally activated acrylic resin. Fifty 4 mm specimens of acrylic resin were obtained using a metallic matrix. The specimens received chemical polishing, were sterilized and then immersed in Sabouraud broth, inoculated with Candida albicans standardized suspension. After 24 hours of incubation at 37°C, the specimens were divided into four groups according to the substance used for disinfection (5% sodium bicarbonate, 0.12% digluconate chlorhexidine, vinegar and Corega Tabs). A control group was included, in which distilled water was used. The adhered microorganisms were dispersed, diluted and plated onto culture media to determine the number of colony-forming units (cfu/mL). The results were analyzed through the Mann-Whitney statistical test at the 5% level of significance. Only 0.12% digluconate chlorhexidine and 5% sodium bicarbonate presented a statistically significant difference (p = 0.0010 and p = 0.0156, respectively) compared to the control group, decreasing the number of cfu/mL. However, when the different disinfecting solutions were compared with each other, only 0.12% digluconate chlorhexidine presented a statistically significant difference in the reduction of cfu/mL. It was concluded that although 0.12% digluconate chlorhexidine was more effective in the reduction of Candida albicans adherence values to thermally activated acrylic resin, 5% sodium bicarbonate also proved to be a viable alternative.

Oxidative stability and α-tocopherol retention in soybean oil with lemon seed extract (Citrus limon) under thermoxidation

The synergistic effect of lemon seed extract with tert-butylhydroquinone (TBHQ) in soybean oil subjected to thermoxidation by Rancimat was investigated, and the influence of these antioxidants on α-tocopherol degradation in thermoxidized soybean oil. Control, LSE (2,400 mg/kg Lemon Seed Extract), TBHQ (50 mg/kg), Mixture 1 (LSE + 50 mg/kg TBHQ) and Mixture 2 (LSE + 25 mg/kg TBHQ) were subjected to 180°C for 20 h. Samples were taken at time 0, 5, 10, 15 and 20 h intervals and analysed for oxidative stability and α-tocopherol content. LSE and Mixtures 1 and 2 showed the capacity of retarding lipid oxidation when added to soya oil and also contributed to α-tocopherol retention in oil heated at high temperatures. However, Mixtures 1 and 2 added to the oil presented a greater antioxidant power, consequently proving the antioxidants synergistic effect.

Effect of accelerated aging on the microhardness and color stability of flexible resins for dentures

Acrylic resins have been widely used due to their acceptable esthetics and desirable characteristics such as easy handling, good thermal conductivity, low permeability to oral fluids and color stability. Flexible resins were introduced on the market as an alternative to the use of conventional acrylic resins in the construction of complete and partial removable dentures. Although these resins present advantages in terms of esthetics and comfort, studies assessing chromatic and microhardness alterations of these materials are still scarce in the related literature. The aim of this study was to evaluate the chromatic and microhardness alterations of two commercial brands of flexible resins in comparison to the conventional resin Triplex when submitted to accelerated aging. The resins were manipulated according to manufacturers' instructions and inserted into a silicone matrix to obtain 21 specimens divided into 3 groups: Triplex, Ppflex and Valplast. Triplex presented the highest microhardness value (p < 0.05) for all the aging periods, which was significantly different from that of the other resins, followed by the values of Valplast and Ppflex. Comparison between the flexible resins (Ppflex and Valplast) revealed a statistically significant difference (p < 0.05) as regards color. The flexible resin Ppflex and the conventional resin Triplex presented no statistically significant difference (p < 0.05) as regards aging. The accelerated aging significantly increased the microhardness values of the resins, with the highest values being observed for Triplex. Valplast presented the greatest chromatic alteration after accelerated aging.

Effect of phosphate-bonded investments on titanium reaction layer and crown fit

This study analyzed the reaction layer and measured the marginal crown fit of cast titanium applied to different phosphate-bonded investments, prepared under the following conditions (liquid concentration/casting temperature): Rema Exakt (RE) - 100%/237°C, 75%/287°C, Castorit Super C (CS)-100%/70°C, 75%/141°C and Rematitan Plus (RP)-100%/430°C (special to titanium cast, as the control group). The reaction layer was studied using the Vickers hardness test, and analyzed by two way ANOVA and Tukey's HSD tests (α = 0.05). Digital photographs were taken of the crowns seated on the die, the misfit was measured using an image analysis system and One-way ANOVA, and Tukey's test was applied (α = 0.05). The hardness decreased from the surface (601.17 VHN) to 150 μm (204.03 VHN). The group CS 75%/141°C presented higher hardness than the other groups, revealing higher surface contamination, but there were no differences among the groups at measurements deeper than 150 μm. The castings made with CS - 100%/70°C presented the lowest levels of marginal misfit, followed by RE -100%/237°C. The conventional investments CS (100%) and RE (100%) showed better marginal fit than RP, but the CS (75%) had higher surface contamination.

Effect of storage in artificial saliva and thermal cycling on Knoop hardness of resin denture teeth

Purpose: This study aimed to evaluate the effect of different storage periods in artificial saliva and thermal cycling on Knoop hardness of 8 commercial brands of resin denture teeth. Methods: Eigth different brands of resin denture teeth were evaluated (Artplus group, Biolux group, Biotone IPN group, Myerson group, SR Orthosit group, Trilux group, Trubyte Biotone group, and Vipi Dent Plus group). Twenty-four teeth of each brand had their occlusal surfaces ground flat and were embedded in autopolymerized acrylic resin. After polishing, the teeth were submitted to different conditions: (1) immersion in distilled water at 37 ± 2 °C for 48 ± 2. h (control); (2) storage in artificial saliva at 37 ± 2 °C for 15, 30 and 60 days, and (3) thermal cycling between 5 and 55 °C with 30-s dwell times for 5000 cycles. Knoop hardness test was performed after each condition. Data were analyzed with two-way ANOVA and Tukey's test (α= .05). Results: In general, SR Orthosit group presented the highest statistically significant Knoop hardness value while Myerson group exhibited the smallest statistically significant mean (P< .05) in the control period, after thermal cycling, and after all storage periods. The Knoop hardness means obtained before thermal cycling procedure (20.34 ± 4.45 KHN) were statistically higher than those reached after thermal cycling (19.77 ± 4.13 KHN). All brands of resin denture teeth were significantly softened after storage period in artificial saliva. Conclusion: Storage in saliva and thermal cycling significantly reduced the Knoop hardness of the resin denture teeth. SR Orthosit denture teeth showed the highest Knoop hardness values regardless the condition tested. © 2010 Japan Prosthodontic Society.