Mechanical Characteristics of Composite Resins Produced by Additive and Subtractive Manufacturing.

INTRODUCTION: The aim of the study was to evaluate the mechanical characteristics of resin composites produced by additive and subtractive manufacturing. METHODS: Six composite resin materials produced by subtractive (Vita Enamic-VE, Cerasmart-CE, Lava Ultimate-LU) and additive manufacturing (Varseo Smile Crown plus-VSC, Saremco Print Crowntec-SPC, Formlabs 3B Permanent crown-FLP) were selected. The three-point bending test was performed, and surface hardness of test specimens was measured. RESULTS: The flexural strength values of CE, SPC and LU test groups were found to be statistically higher when compared to VE, FLP and VSC test groups (p⟨0.0033). The modulus of elasticity values of the test specimens was listed as VE>LU>CE>SPC>FLP>VSC. The FLP group [35.11(4.46)] had the lowest surface hardness values, whereas the VE group [252.50 (21.5)] had the highest values. Other groups were listed as LU⟩CE⟩SPC⟩VSC in terms of surface hardness. CONCLUSIONS: According to the ISO 6872:2015, the flexural strengths of all resin composites were found to be acceptable for single unit fixed restorations. However, the VSC group's flexural strength is suitable for inlay, onlay, veneer restorations or single-unit anterior fixed dental prostheses. Also, VSC may not be a suitable choice for posterior restorations due to its low flexural strength.

Investigation of Effects of Two Chronic Stress Protocols on Depression-Like Behaviors and Brain Mineral Levels in Female Rats: an Evaluation of 7-Day Immobilization Stress.

We aimed to investigate the effects of two different chronic immobilization stress protocols on depression-related behaviors and brain mineral levels. Adult female Wistar albino rats were divided into 3 groups as follows (n = 10/group): control, immobilization stress-1 (45 min daily for 7 days), and immobilization stress-2 (45 min twice a day for 7 day). Stress-related behavior was evaluated by means of the forced swimming test (FST) and open field test (OFT). Minerals were analyzed using an inductively coupled plasma mass spectrometer. In the FST, swimming and immobility were significantly lower in the immobilization stress-1 and immobilization stress-2 groups. The climbing duration of the immobilization stress-2 group was higher than the control group. In the OFT, percentage of time spent in the central area was significantly lower in the immobilization stress-1 and immobilization stress-2 groups. Values of latency to center area, rearing, and grooming did not significantly differ between groups. In the immobilization stress-1 group, zinc was lower, and iron, copper, and manganese were higher than the control group. In the immobilization stress-2 group, copper and manganese were higher, and phosphate was lower than the control group. Our results showed that depression-related behaviors were more dominant in the immobilization stress-1 group. A decrease in the brain zinc level was valid only for the immobilization stress-1 group. These results point to the role of low brain zinc levels in the pathophysiology of depression.

Synthesis, anticonvulsant and antimicrobial activities of some new [1-(2-naphthyl)-2-(pyrazol-1-yl)ethanone]oxime ethers.

In this study, 12 new oxime ether derivatives, which were expected to show anticonvulsant and antimicrobial activities, were synthesized. Oxime ether derivatives were synthesized by the reaction of various alkyl halides with 1-(2- naphthyl)-2-(pyrazol-1-yl)ethanone oxime. Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazol (ScM) seizure tests, while neurological disorders were evaluated using rotorod toxicity test according to the ASP of NIH. Compound 1, 6 and 7 showed anticonvulsant activity at 300 mg/kg dose at 4 h, but compounds 1 and 7 showed toxicity at 300 mg/kg dose at half an hour. Antimicrobial activities of the compounds were also determined using agar microdilution method. Compound 1 and 5 were found to have the highest antifungal activity among the other compounds.

Dynamic Hedgehog signalling pathway activity in germline stem cells.

Although the contribution of Hedgehog (Hh) signalling to stem cell development and oncogenesis is well recognised, its importance for spermatogonial stem cells (SSCs) has not been established. Here we interrogate adult rat SSCs using an established model in which only undifferentiated spermatogonial cells remain in the testis at 15 weeks following irradiation, and spermatogonial differentiation is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH-ant) administration. Synthesis of Hh pathway components in untreated adult rat testes was compared with that in irradiated testes prior to and after GnRH-ant exposure using in situ hybridization. In adult testes with complete spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization. Spermatogenic cells were identified as sites of Hh signalling through detection of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the key downstream target of Hh signalling, Gli1 and the Hh transcriptional activator, Gli2. Remarkably, the undifferentiated spermatogonia present in irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2, revealing the potential for an autocrine Hh signalling loop to sustain undifferentiated spermatogonial cells. These transcripts became undetectable by in situ hybridization following GnRH-ant induction of spermatogonial differentiation, however, detection of Gli1 protein in spermatogonia in all groups indicates that Hh signalling is sustained. This is the first evidence of active Hh signalling in mammalian male germline stem cells, as has been documented for some cancer stem cells.

Table for two: diabetes distress and diet-related interactions of married patients with diabetes and their spouses.

In adjusting to chronic illness, patients often negotiate new or altered daily routines within a dynamic family context. Yet, the responses of family members to the disease and its management are understudied. The authors investigated patients with Type 2 diabetes and their spouses (N = 55 couples) and examined the association of diet-related interactions (i.e., diet-related support, diet-related pressure, and frequency of sharing meals together) with each partner's adjustment to the illness context (i.e., diabetes distress). All spouses (100%) reported providing some type of diet-related support to their partners with diabetes in the past month, and many reported exerting pressure to improve their partners' diet choices (60%). In addition, many couples (64%) indicated that they frequently shared meals together in the past month. For spouses, their provision of diet-related pressure was associated (positively) with their diabetes distress. Frequently sharing meals was associated with less diabetes distress among patients, even after controlling for their glycemic control and diet adherence. Findings reveal that spouses of patients with diabetes are actively involved in illness management with their partners, and these activities are associated with their own diabetes distress and with that of their ill partners.

Orexins activates protein kinase C-mediated Ca(2+) signaling in isolated rat primary sensory neurons.

Previous results have suggested that orexins causes a rise of intracellular free calcium ([Ca(2+)](i)) in cultured rat dorsal root ganglion (DRG) neurons, implicating a role in nociception, but the underlying mechanism is unknown. Hence, the aim of the present study was to investigate whether the orexins-mediated signaling involves the PKC pathways in these sensory neurons. Cultured DRG neurons were loaded with 1 micromol Fura-2 AM and [Ca(2+)](i) responses were quantified by the changes in 340/380 ratio using fluorescence imaging system. The orexin-1 receptor antagonist SB-334867-A (1 microM) inhibited the calcium responses to orexin-A and orexin-B (59.1+/-5.1 % vs. 200 nM orexin-A, n=8, and 67+/-3.8 % vs. 200 nM orexin-B, n=12, respectively). The PKC inhibitor chelerythrine (10 and 100 microM) significantly decreased the orexin-A (200 nM)-induced [Ca(2+)](i) increase (59.4+/-4.8 % P<0.01, n=10 and 4.9+/-1.6 %, P<0.01, n=9) versus response to orexin-A). It was also found that chelerythrine dose-dependently inhibited the [Ca(2+)](i) response to 200 nM orexin-B. In conclusion, our results suggest that orexins activate intracellular calcium signaling in cultured rat sensory neurons through PKC-dependent pathway, which may have important implications for nociceptive modulation and pain.

Synthesis and molecular modeling of some novel hexahydroindazole derivatives as potent monoamine oxidase inhibitors.

A novel series of 2-thiocarbamoyl-2,3,4,5,6,7-hexahydro-1H-indazole and 2-substituted thiocarbamoyl-3,3a,4,5,6,7-hexahydro-2H-indazoles derivatives were synthesized and investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). The target molecules were identified on the basis of satisfactory analytical and spectra data (IR, (1)H NMR, (13)C NMR, (2)D NMR, DEPT, EI-MASS techniques and elemental analysis). Synthesized compounds showed high activity against both the MAO-A (compounds 1d, 1e, 2c, 2d, 2e) and the MAO-B (compounds 1a, 1b, 1c, 2a, 2b) isoforms. In the discussion of the results, the influence of the structure on the biological activity of the prepared compounds was delineated. It was suggested that non-substituted and N-methyl/ethyl bearing compounds (except 2c) increased the inhibitory effect and selectivity toward MAO-B. The rest of the compounds, carrying N-allyl and N-phenyl, appeared to select the MAO-A isoform. The inhibition profile was found to be competitive and reversible for all compounds. A series of experimentally tested (1a-2e) compounds was docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The autodock 4.01 program was employed to perform automated molecular docking. In order to see the detailed interactions of the docked poses of the model inhibitors compounds 1a, 1d, 1e and 2e were chosen because of their ability to reversibly inhibit the MAO-B and MAO-A and the availability of experimental inhibition data. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Excellent to good correlations between the calculated and experimental K(i) values were obtained. In the docking of the MAO-A complex, the trans configuration of compound 1e made various very close interactions with the residues lining the active site cavity these interactions were much better than those of the other compounds tested in this study. This tight binding observation may be responsible for the nanomolar inhibition of form of MAOA. However, it binds slightly weaker (experimental K(i)=1.23 microM) to MAO-B than to MAO-A (experimental K(i)=4.22 nM).

Synthesis, characterization and anti-inflammatory activity of new 5-(3,4-dichlorophenyl)-2-(aroylmethyl) thio-1,3,4-oxadiaxoles.

Several 5-(3,4-dichlorophenyl)-2-(aroylmethyl)thio-1,3,4-oxadiazoles were synthesized and characterized by elemental analyses, IR and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carregeenan-induced edema in rat paw. In addition, ulcerogenic activity was determined. The anti-inflammatory data scoring showed that compounds 5e, 5f and 5g, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5f was comparable to that of the reference drug indometacin (CAS 53-86-1).

Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats.

We have investigated effects of letrozole, an aromatase inhibitor, on spatial learning and memory, expression of neural cell adhesion molecules (NCAM) and catecholaminergic neurotransmitters in the hippocampus and cortex of female rats. In the intact model, adult Sprague-Dawley rats were divided into four groups (n=8). Control received saline alone. Letrozole was administered to the animals in the second and third groups by daily oral gavage at 0.2 and 1 mg/kg doses, respectively, for 6 weeks. Another group of letrozole-treated rats was allowed to recover for 2 weeks. In the second model, 24 rats were ovariectomized (ovx) and the first group served as control. The second group received letrozole (1 mg/kg) for 6 weeks. Ovx rats in the third group were given letrozole (1 microg/kg) plus estradiol (E(2)) (10 microg/rat). At the end, all rats were tested in a spatial version of the Morris water maze. Then they were decapitated and the brains rapidly removed. Catecholamine concentrations were determined by high performance liquid chromatography with electrochemical detection. NCAM 180, 140 and 120 isoforms were detected by Western blotting. Uterine weights were significantly reduced by letrozole in a dose-dependent manner (P<0.01) which returned to control values following 2 weeks of recovery (P<0.05). Serum E(2) levels followed a similar course (P<0.01). Although improvement in spatial learning performance of letrozole-treated rats was not statistically significant, the high-dose letrozole-treated group remained significantly longer in the target quadrant compared with the control (P<0.05). Administration of letrozole to ovx animals significantly reduced the latency (P<0.001) and increased the probe trial performance compared with ovx controls (P<0.05). Letrozole increased expression of NCAM 180 and NCAM 140 in both hippocampus and cortex of intact rats. In the cortex samples of ovx animals, NCAM 180 was overall lower than the intact control values (P<0.05). Noradrenaline, dopamine and their metabolites were decreased in the hippocampus of the letrozole-treated group (P<0.01). Letrozole had differential effects on noradrenaline and dopamine content in the cortex. It appears that inhibition of estrogen synthesis in the brain may have beneficial effects on spatial memory. We suggest that structural changes such as NCAM expression and catecholaminergic neurotransmitters in the hippocampus and prefrontal cortex may be the neural basis for estrogen-dependent alterations in cognitive functions.

The zonal distributions of alkaline phosphatase, adenosine triphosphatase, laminin, fibronectin and chondroitin 4-sulphate in growing rat humerus proximal epiphyseal cartilage: a histochemical and an immunohistochemical study.

Although there are many studies about epiphyseal cartilage extracellular matrix (ECM) macromolecules in bone formation, studies of their distribution and role in the mineralization of these components in growing rat humerus proximal epiphyseal cartilage have not been sufficiently detailed. The aim of this study was to determine the distributions of alkaline phosphatase (ALP), adenosine triphosphatase (ATPase), laminin, fibronectin and chondroitin 4-sulphate in growing rat humerus proximal epiphyseal cartilage. The rats were killed by cervical dislocation, and the humeri were removed, sectioned (6 and 10 microm) on a cryotome or paraffin microtome, and stained using histochemical and immunohistochemical methods. ALP and ATPase were markedly observed in the hypertrophy and calcifying cartilage. In addition, ATPase was found to be very strongly positive in the tangential zone of articular cartilage. Results of immunohistochemical staining for laminin, fibronectin and chondroitin 4-sulphate showed that the immunostaining was the heaviest in the tangential zone of articular cartilage. In growing epiphyseal plates, there were differences in the density of these macromolecules of chondrocytes as a function of the maturation process. In conclusion, these ECM macromolecules of epiphyseal cartilage may regulate the cell-cell and cell-matrix interactions as well as the matrix calcification during the ossification of epiphyseal cartilage.