Azilsartan Attenuates 3-Nitropropinoic Acid-Induced Neurotoxicity in Rats: The Role of IĸB/NF-ĸB and KEAP1/Nrf2 Signaling Pathways.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by motor, psychiatric and cognitive symptoms. Injection of 3-nitropropionic acid (3-NP) is a widely used experimental model for induction of HD. The current study aimed to inspect the potential neuroprotective properties of azilsartan (Azil), an angiotensin II type 1 receptor blocker (ATR1), in 3-NP-induced striatal neurotoxicity in rats. Rats were randomly allocated into five groups and treated for 14 days as follows: group I received normal saline; group II received Azil (10 mg/kg, p.o.); group III received 3-NP (10 mg/kg, i.p); group IV and V received Azil (5 or 10 mg/kg, p.o, respectively) 1 h prior to 3-NP injection. Both doses of Azil markedly attenuated motor and behavioural dysfunction as well as striatal histopathological alterations caused by 3-NP. In addition, Azil balanced striatal neurotransmitters levels as evidenced by the increase of striatal gamma-aminobutyric acid content and the decrease of glutamate content. Azil also amended neuroinflammation and oxidative stress via modulating IĸB/NF-ĸB and KEAP1/Nrf2 downstream signalling pathways, as well as reducing iNOS and COX2 levels. Moreover, Azil demonstrated an anti-apoptotic activity by reducing caspase-3 level and BAX/BCL2 ratio. In conclusion, the present study reveals the neuroprotective potential of Azil in 3-NP-induced behavioural, histopathological and biochemical changes in rats. These findings might be attributed to inhibition of ATR1/NF-κB signalling, modulation of Nrf2/KEAP1 signalling, anti-inflammatory, anti-oxidant and anti-apoptotic properties.

Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi.

Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.

Hypoxia-inducible factor 1 alpha and nuclear-related receptor 1 as targets for neuroprotection by albendazole in a rat rotenone model of Parkinson's disease.

Hypoxia-inducible factor-1 alpha (HIF-1α) and nuclear receptor related-1 (Nurr1) play pivotal roles in the development and survival of dopaminergic neurons, and deficiencies in these genes may be involved in Parkinson's disease (PD) pathogenesis. Recently, anthelminthic benzimidazoles were shown to promote HIF-1α transcription in vitro and were proposed to activate Nurr1 via their benzimidazole group. Therefore, the aim of this study was to explore the neuroprotective effects of albendazole (ABZ), an anthelminthic benzimidazole, in a rotenone model of Parkinson's disease (PD). Rotenone (1.5 mg/kg) was subcutaneously injected into rats every other day for a period of 21 days, resulting in the development of the essential features of PD. In addition to rotenone, ABZ (10 mg/kg) was administered orally starting from the 11th day. Treatment of rats with ABZ markedly mitigated rotenone-induced histological alterations in substantia nigra (SN), restored striatal dopamine (DA) level and motor functions and decreased the expression of α-synuclein (a disease marker protein). ABZ also enhanced expression of Hypoxia-inducible factor-1 alpha (HIF-1α) in the SN along with its downstream target, vascular endothelial growth factor, promoting neuronal survival. Similarly, ABZ augmented nuclear receptor related-1 (Nurr1) expression in the SN and increased transcriptional activation of Nurr1-controlled genes, which are essential for regulation of DA synthesis; additionally, expression of neurotoxic proinflammatory cytokines that induce neuronal death was suppressed. In conclusion, the present study suggests that ABZ exerts a neuroprotective effect in a rotenone-induced PD model associated with HIF-1α and Nurr1 activation and thus may be a viable candidate for treating PD.

A novel patient-derived xenograft model for claudin-low triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) subtypes are clinically aggressive and cannot be treated with targeted therapeutics commonly used in other breast cancer subtypes. The claudin-low (CL) molecular subtype of TNBC has high rates of metastases, chemoresistance and recurrence. There exists an urgent need to identify novel therapeutic targets in TNBC; however, existing models utilized in target discovery research are limited. Patient-derived xenograft (PDX) models have emerged as superior models for target discovery experiments because they recapitulate features of patient tumors that are limited by cell-line derived xenograft methods. METHODS: We utilize immunohistochemistry, qRT-PCR and Western Blot to visualize tumor architecture, cellular composition, genomic and protein expressions of a new CL-TNBC PDX model (TU-BcX-2O0). We utilize tissue decellularization techniques to examine extracellular matrix composition of TU-BcX-2O0. RESULTS: Our laboratory successfully established a TNBC PDX tumor, TU-BCX-2O0, which represents a CL-TNBC subtype and maintains this phenotype throughout subsequent passaging. We dissected TU-BCx-2O0 to examine aspects of this complex tumor that can be targeted by developing therapeutics, including the whole and intact breast tumor, specific cell populations within the tumor, and the extracellular matrix. CONCLUSIONS: Here, we characterize a claudin-low TNBC patient-derived xenograft model that can be utilized for therapeutic research studies.

Influence of clinical use on physical-structural surface properties and electrochemical potential of NiTi endodontic instruments.

AIM: To investigate the surface morphology and electrochemical potential of superelastic (SE), M-Wire (MW) and shape memory technology (SMT) NiTi instruments before and after single clinical use in vivo. METHODOLOGY: A total of 60 ProTaper Universal F2 (PTU-SE), ProTaper Next X2 (PTN-MW), Typhoon (TYP), Hyflex (HF) and Vortex Blue (VB), the last three SMT, and size 25, .06 taper (n = 6 of each type) files were examined. Scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS) and electrochemical potential analysis were employed before and after clinical use. Statistical analysis was performed with one-way analysis of variance and Bonferroni's post hoc test. Significance was determined at the 95% confidence level for both tests. RESULTS: SEM observations of new instruments indicated the presence of marks left by the machining process during manufacturing and EDS revealed the existence of an oxide coating on shape memory instruments. After clinical use, the five types were associated with propagation of transverse cracks 3 mm from the tip. The surface oxide layer of TYP, HF and VB instruments had microcracks in multiple directions, whilst TYP and HF had fragmentation in chip form of the oxide layer. EDS analysis demonstrated a significant reduction of the oxide layer in shape memory instruments, except for VB. Electrochemical potentials were higher for shape memory instruments than for M-Wire and superelastic NiTi instruments, respectively (P < 0.05). CONCLUSIONS: It appears that shape memory technology NiTi instruments have a dysfunctional oxide layer after clinical use. Additionally, they featured higher electrochemical potential relative to NiTi instruments manufactured from M-Wire, and conventional superelastic NiTi alloy.

Renoprotective effects of montelukast in an experimental model of cisplatin nephrotoxicity in rats.

Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS-drawn nephrotoxicity remains obscure. Therefore, adult male Sprague-Dawley rats were orally given ML (10 and 20 mg/kg/day) 5 days before and after single CIS (5 mg/kg; i.p.) treatment. ML returned blood urea nitrogen, as well as serum creatinine and gamma glutamyl transferase that were elevated by CIS to normal level. The improved kidney function tests corroborated the attenuation of CIS renal injury at the microscopical level. It also reduced serum/renal nitric oxide and renal hemeoxygenase-1. Meanwhile, ML hindered the raised levels of serum endothelin-1, serum and renal tumor necrosis factor-α, and monocyte chemoattractant protein-1. These effects were associated by deceased caspase-3 expression in kidney after ML treatment. In conclusion, ML guards against CIS-induced nephrotoxicity via anti-inflammatory and antiapoptotic properties.

Phenotypic Screening In Vitro of Novel Aromatic Amidines against Trypanosoma cruzi.

The current treatment of Chagas disease (CD), based on nifurtimox and benznidazole (Bz), is unsatisfactory. In this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. Ten novel amidines were tested for their activities against bloodstream trypomastigote (BT) and amastigote forms of Trypanosoma cruzi (Y and Tulahuen strains) and their toxicities for mammalian host cells (L929 cells and cardiac cells). Seven of 10 molecules were more active than Bz against BT, with the most active compound being the diamidine DB2267 (50% effective concentration [EC50] = 0.23 µM; selectivity index = 417), which was 28-fold more active and about 3 times more selective than the standard drug. Five of the six monoamidines were also more active than Bz. The combination of DB2267 and DB2236 in fixed-ratio proportions showed an additive effect (sum of fractional inhibitory concentrations < 4) on BT. Interestingly, when intracellular forms were exposed to DB2267, its activity was dependent on the parasite strain, being effective (EC50 = 0.87 ± 0.05 µM) against a discrete typing unit (DTU) II strain (strain Y) but not against a representative DTU VI strain (strain Tulahuen) even when different vehicles (ß-cyclodextrin and dimethyl sulfoxide) were used. The intrinsic fluorescence of several diamidines allowed their uptake to be studied. Testing of the uptake of DB2236 (inactive) and DB2267 (active) by amastigotes of the Y strain showed that the two compounds were localized intracellularly in different compartments: DB2236 in the cytoplasm and DB2267 in the nucleus. Our present data encourage further studies regarding the activities of amidines and provide information which will help with the identification of novel agents for the treatment of CD.

In vitro assessment of the genotoxic and cytotoxic effects of boiled juice (tucupi) from Manihot esculenta Crantz roots.

The population of Pará (a state in Brazil) has a very characteristic food culture, as a majority of the carbohydrates consumed are obtained from cassava (Manihot esculenta Crantz) derivatives. Tucupi is the boiled juice of cassava roots that plays a major role in the culinary footprint of Pará. Before boiling, this juice is known as manipueira and contains linamarin, a toxic glycoside that can decompose to hydrogen cyanide. In this study, the cytotoxic and genotoxic effects of tucupi on cultured human lymphocytes were assessed using the comet assay and detection of apoptosis and necrosis by differential fluorescent staining with acridine orange-ethidium bromide. Tucupi concentrations (v/v) were determined using the methylthiazole tetrazolium biochemical test. Concentrations of tucupi that presented no genotoxic effects (2, 4, 8, and 16%) were used in our experiments. The results showed that under our study conditions, tucupi exerted no genotoxic effects; however, cytotoxic effects were observed with cell death mainly induced by necrosis. These effects may be related to the presence of hydrogen cyanide in the juice.

Validated finite element analyses of WaveOne Endodontic Instruments: a comparison between M-Wire and NiTi alloys.

AIM: To validate torsional analysis, based on finite elements, of WaveOne instruments against in vitro tests and to model the effects of different nickel-titanium (NiTi) materials. METHODOLOGY: WaveOne reciprocating instruments (Small, Primary and Large, n = 8 each, M-Wire) were tested under torsion according to standard ISO 3630-1. Torsional profiles including torque and angle at fracture were determined. Test conditions were reproduced through Finite Element Analysis (FEA) simulations based on micro-CT scans at 10-µm resolution; results were compared to experimental data using analysis of variance and two-sided one sample t-tests. The same simulation was performed on virtual instruments with identical geometry and load condition, based on M-Wire or conventional NiTi alloy. RESULTS: Torsional profiles from FEA simulations were in significant agreement with the in vitro results. Therefore, the models developed in this study were accurate and able to provide reliable simulation of the torsional performance. Stock NiTi files under torsional tests had up to 44.9%, 44.9% and 44.1% less flexibility than virtual M-Wire files at small deflections for Small, Primary and Large instruments, respectively. As deflection levels increased, the differences in flexibility between the two sets of simulated instruments decreased until fracture. Stock NiTi instruments had a torsional fracture resistance up to 10.3%, 8.0% and 7.4% lower than the M-Wire instruments, for the Small, Primary and Large file, respectively. CONCLUSION: M-Wire instruments benefitted primarily through higher material flexibility while still at low deflection levels, compared with conventional NiTi alloy. At fracture, the instruments did not take complete advantage of the enhanced fractural resistance of the M-Wire material, which determines only limited improvements of the torsional performance.

Ellagic acid antiinflammatory and antiapoptotic potential mediate renoprotection in cisplatin nephrotoxic rats.

Ellagic acid (EA) renoprotective effect against cisplatin (CIS)-induced nephrotoxicity remains elusive. Therefore, male Sprague-Dawley rats received CIS alone or EA (10 and 30 mg/kg, p.o.) for 5 days before and after CIS injection. CIS increased serum levels of blood urea nitrogen, creatinine, γ-glutamyl transferase, and reduced those of albumin and total protein. It also raised serum endothelin-1, as well as serum and renal nitric oxide, tumor necrosis factor-α, and monocyte chemoattractant protein-1. CIS enhanced the renal caspase-3, hemeoxygenase (HO)-1, nuclear factor-κB, and inducible nitric oxide. EA hampered CIS-induced nephrotoxicity manifested by an enhancement of the glomerular filtration rate which was associated by the reduction of inflammatory mediators and the apoptotic marker in the serum and/or kidney. The present study discloses that EA suppresses HO-1 and, its renoprotection is also linked to its anti-inflammatory and antiapoptotic properties, as well as the reduction of nitric oxide and endothelin-1.

Flexibility and torsional behaviour of rotary nickel-titanium PathFile, RaCe ISO 10, Scout RaCe and stainless steel K-File hand instruments.

AIM: To assess and compare the flexibility and torsional resistance of PathFile, RaCe ISO 10 and Scout RaCe instruments in relation to stainless steel K-File hand instruments. METHODOLOGY: Rotary PathFile (sizes 13, 16 and 19; .02 taper), Race ISO 10 (size 10; 0.02, 0.04 and 0.06 tapers), Scout RaCe (sizes 10, 15 and 20; 0.02 taper) and hand K-File (sizes 10, 15 and 20; 0.02 taper) instruments were evaluated. Alloy chemical composition, phases present and transformation temperatures were determined for the NiTi instruments. For all instruments, diameters at each millimetre from the tip as well as cross-sectional areas at 3 mm from the tip were measured based on ANSI/ADA Specification No. 101 using image analysis software. Resistance to bending and torsional resistance were determined according to specification ISO 3630-1. Vickers microhardness measurements were also taken in all instruments to assess their strength. Data were analysed using analysis of variance (α = 0.05). RESULTS: The alloys used in the manufacture of the three types of NiTi instruments had approximately the same chemical composition, but the PathFile instruments had a higher Af transformation temperature and contained a small amount of B19' martensite. All instruments had diameter values within the standard tolerance. The bending and torsional resistance values were significantly increased relative to the instrument diameter and cross-sectional area. CONCLUSIONS: PathFile instruments were the most flexible and the least torque resistant, whilst the stainless steel instruments were the least flexible although they were more torque resistant than the NiTi instruments.

Modulation of expressivity in PDGFRB-related infantile myofibromatosis: a role for PTPRG?

Infantile myofibromatosis is a rare genetic disorder characterized by the development of benign tumors in the skin, muscle, bone, and viscera. The molecular pathogenesis is still incompletely known. An autosomal dominant form had been reported as causally related with mutations in the gene for platelet-derived growth factor receptor beta (PDGFRB). We report here two siblings with infantile myofibromatosis and with a PDGFRB mutation identified by exome sequence analysis. However, the unaffected mother also had the same PDGFRB mutation. We showed that both children had also inherited from their healthy father a heterozygous mutation in the gene for receptor protein tyrosine phosphatase gamma (PTPRG), an enzyme known to dephosphorylate PDGFRB. We suggest that in this family, the additional mutation in PTPRG may explain the full phenotypic penetrance in the siblings affected, in comparison with the unaffected mother.

Optimization of a surfactant-free antioxidant formulation using response surface methodology.

Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet radiation-mediated oxidative damage. In previous studies, a Castanea sativa leaf ethanol:water (7:3) extract exhibited scavenging activity against different reactive oxygen species that are thought to contribute to oxidative damage in the skin. Its stability was shown to be enhanced in the presence of glycerine, and therefore a glycerine-based formulation with Carbopol 940 and liquid paraffin (LP) was developed as base. In this work, the influence of the glycerine and LP contents on the textural properties of the topical base and on the antioxidant activity of the formulation with C. sativa extract was evaluated using response surface methodology after 30 d storage at 20 °C and 40 °C. The textural analysis was performed in a texturometer, by carrying out a spreadability test. Paretto charts showed that both glycerine and LP contents significantly influenced the textural properties of the formulations (p < 0.05). LP presented the major influence. DPPH scavenging activity was not related to any of the studied ingredients. These conclusions were valid both for 20 °C and 40 °C storage. This optimization study provided valuable information to support the development of a semisolid base for C. sativa extract leading to the conclusion that the selection of these ingredients contents can be guided exclusively by the desirable textural properties.

The influence of simulated clinical use on the flexibility of rotary ProTaper Universal, K3 and EndoSequence nickel-titanium instruments.

AIM: To investigate the influence of cyclic flexural and torsional loading on the flexibility of ProTaper Universal, K3 and EndoSequence nickel-titanium instruments, in view of the hypothesis that these types of loading would decrease the flexibility of the selected NiTi rotary files. METHODOLOGY: The instruments evaluated were S2 and F1 ProTaper Universal, sizes 20 and 25, .06 taper K3, and sizes 20 and 25, .06 taper EndoSequence. Flexibility was determined by 45° bending tests according to ISO 3630-1 specification. Values of the bending moment (MB ) obtained with new instruments were considered as the control group (CG). Bending tests were then conducted in instruments previously fatigued to one-fourth and three-fourths of their average fatigue life (fatigue groups, FG» and FG¾), as well as after cyclic torsional loading (torsional group, TG). Fatigue tests were carried out in a bench device that allowed the files to rotate freely inside an artificial canal with an angle of curvature of 45° and a radius of 5 mm. Cyclic torsional loading tests were performed that entailed rotating the instrument from zero angular deflection to 180° and then returning to zero applied torque in 20 cycles. Data were analysed using one-way analysis of variance at a significance level of 5%. RESULTS: Simulated clinical use by means of flexural fatigue tests did not affect the flexibility of the instruments, except for a significant increase in flexibility observed in a few instruments (P < 0.05). In addition, comparative statistical analyses between the values of MB measured in new instruments and after cyclic torsional loading showed no significant differences between them (P > 0.05). CONCLUSIONS: The flexibility of rotary ProTaper Universal, K3 and EndoSequence NiTi instruments, measured in bending tests, was not adversely affected by simulated clinical use in curved root canals.

Physical and mechanical properties of twisted or ground nickel-titanium instruments.

AIM: To compare the flexibility, torsional resistance and structural and dimensional characteristics of instruments produced by twisting with those of a geometrically similar nickel-titanium (NiTi) system produced by a grinding process. METHODOLOGY: The mean diameters along the flute and the pitch length of size 25, .04 taper, size 25, .06 taper, and size 25, .08 taper Twisted File (TF) (SybronEndo, Orange, CA, USA), and size 25, .04 taper, and size 25, .06 taper RaCe instruments (FKG, La Chaux-de-Fonds, Switzerland) (n = 10 each) were measured according to ANSI/ADA specification No. 101. Two pairs of instruments were found to have similar diameters at 3 mm from the tip: TF size 25, .06 taper and RaCe size 25, .04 taper, and TF size 25, .08 taper and RaCe size 25, .06 taper. The cross-sectional areas at 3 mm from the tip were determined. These instruments were then submitted to energy-dispersive X-ray spectroscopy, X-ray diffraction, differential scanning calorimetry (DSC), and Vickers microhardness measurements. Bending moment at 45° and maximum torque at fracture were measured (n = 10) according to specification ISO 3630-1. Data were analysed using analysis of variance (α = 0.05). RESULTS: The two types of instruments had approximately the same chemical composition, phase constitution, and austenite finishing temperatures. TF instruments had significantly (P ≤ 0.001) lower Vickers microhardness values and were more flexible than RaCe instruments (P = 0.016), but had similar (TF size 25, .08 taper and RaCe size 25, .06 taper, P = 0.916) or significantly higher (TF size 25, .06 taper and RaCe size 25, .04 taper, P ≤ 0.001) torsional resistance. CONCLUSIONS: Comparison of TF and RaCe instruments of similar measured dimensions revealed that the different manufacturing methods employed for producing these instruments gave rise to different mechanical behaviours.

Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa).

Iron is the most important metallic chemical element on Earth. Poisoning caused by excessive iron in humans has been associated with pulmonary diseases including neoplasms caused by inhalation of iron oxides. The involvement of iron in neurodegenerative processes has already been described. DNA alterations are induced by iron and other chemical compounds containing this metal; however, the data are controversial and the mechanism by which iron induces mutagenesis remains unknown. This study assessed in vitro iron-induced cytotoxic and genotoxic responses in an astrocytic cell line. Short- and long-term cytotoxicity and genotoxicity were evaluated with the Cell Proliferation Kit II and micronucleus test, respectively. Results indicated that the highest concentration of iron sulfate tested was cytotoxic in long-term cytotoxic assays and increased micronucleus frequency in comparison to controls. The significant cytotoxicity observed here might be due to the intrinsic ability of iron to induce apoptosis and possible changes in cell cycle kinetics; the genotoxic effects are probably due to the oxidant properties of iron itself. This was the first study to investigate the induction of micronuclei by iron in central nervous system cells.

Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).

There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions.

Diverse effects of variant doses of dexamethasone in lithium-pilocarpine induced seizures in rats.

Corticosteroids are used in the management of several epileptic aliments; however, their effectiveness in combating seizures remains controversial, with pro- and anti-convulsive effects ascribed. The current study aimed to address the modulatory effect of dexamethasone (DEX) utilizing 3 dose levels (5, 10, and 20 mg/kg body mass of male Wistar rat) in the rat lithium-pilocarpine (Li-PIL) epilepsy model. Li-PIL induced seizures that were associated with neuronal cell loss in the CA3 region, and increased prostaglandin (PG)E(2), tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide, and neutrophil infiltration in the hippocampus. However, Li-PIL compromised the oxidant-antioxidant balance of the hippocampus. Effective anticonvulsant activity was only observed with 10 mg DEX/kg body mass, which reduced seizure production and incidence, as well as neuronal cell loss in the CA3 region. At this anticonvulsant dose, enhancements in the antioxidant system and IL-10, as well as suppression of altered inflammatory markers were observed. Conversely, doubling the dose showed a tendency to shorten seizure latency, and neither affected seizure incidence nor CA3 neuronal cell loss. These effects were associated with an increase in levels of PGE(2) and TNF-α. The present study found a lack of protection at 5 mg DEX/kg body mass, an anticonvulsant effect at 10 mg/kg, and a loss of protection at 20 mg/kg in the Li-PIL epilepsy model, which indicates that there is an optimal dose of DEX for preventing the induction of seizures.

Physical and mechanical properties of a thermomechanically treated NiTi wire used in the manufacture of rotary endodontic instruments.

AIM: To compare physical and mechanical properties of one conventional and one thermomechanically treated nickel-titanium (NiTi) wire used to manufacture rotary endodontic instruments. METHODOLOGY: Two NiTi wires 1.0 mm in diameter were characterized; one of them, C-wire (CW), was processed in the conventional manner, and the other, termed M-Wire (MW), received an additional heat treatment according to the manufacturer. Chemical composition was determined by energy-dispersive X-ray spectroscopy, phase constitution by XRD and the transformation temperatures by DSC. Tensile loading/unloading tests and Vickers microhardness measurements were performed to assess the mechanical behaviour. Data were analysed using analysis of variance (α = 0.05). RESULTS: The two wires showed approximately the same chemical composition, close to the 1 : 1 atomic ratio, and the ß-phase was the predominant phase present. B19' martensite and the R-phase were found in MW, in agreement with the higher transformation temperatures found in this wire compared with CW, whose transformation temperatures were below room temperature. Average Vickers microhardness values were similar for MW and CW (P = 0.91). The stress at the transformation plateau in the tensile load-unload curves was lower and more uniform in the M-Wire, which also showed the smallest stress hysteresis and apparent elastic modulus. CONCLUSIONS: The M-Wire had physical and mechanical properties that can render endodontic instruments more flexible and fatigue resistant than those made with conventionally processed NiTi wires.

Flexibility and torsional resistance of three nickel-titanium retreatment instrument systems.

AIM: To assess the dimensional characteristics, flexibility and torsional behaviour of nickel-titanium retreatment instruments. METHODOLOGY: Using image analysis software and high-resolution digital images, the instrument length, tip angle, diameter at 3 mm from the tip and the distance between the blades (pitch length) of the following eight instruments were measured (n = 12 for each measurement parameter): the ProTaper Universal retreatment (PTU-R) D1, D2 and D3 instruments; the R-Endo R1, R2 and R3 retreatment instruments; and the Mtwo retreatment (Mtwo-R) sizes 25 and 15 retreatment instruments. Maximum torque and the angular deflection at fracture as well as the bending moment at 45° were measured (n = 12) according to the International Standards Organisation (ISO) specification number 3630-1. Data were analysed using the analysis of variance (α = 0.05). RESULTS: The length of the active part of the instruments was found to vary according to the depth of the canal into which they were designed to reach. The pitch length also increased along the active length. The PTU-R D1 and the Mtwo-R instruments had active tips. Measurements of the bending moment at 45° revealed that the Mtwo-R 15 instrument was the most flexible, whereas the PTU-R D1 was the least flexible. The maximum torque tended to increase as the instrument diameter at 3 mm from the tip increased, whereas the angular deflection at fracture varied in the opposite direction. CONCLUSIONS: The geometrical characteristics of the retreatment instruments and their flexibility and torsion behaviour were consistent with their intended clinical application.