KE Group Research Articles

Does krill oil enhancing the new bone formation in orthopedically expanded median palatal suture in rat model? A micro-CT and immunohistochemical analysis

BackgroundThe purpose of this study was to assess the effects of systemically given krill oil (KO) on the development of new bone formation in the sutura palatina media following rapid maxillary expansion (RME).Methods28 4–5 week-old male Wistar albino rats were randomly divided into 4 groups: Control (C), Only Expansion (OE) (no supplement but undergoing expansion and retention), KE (supplemented during both the expansion and retention phases), Krill Oil Nursery Group (KN) (supplemented during the 40-day nursery phase as well as during the expansion and retention phases). A 5-day RME was followed by a 12-day retention period. All rats were euthanized simultaneously. Micro-computerized tomography (Micro-CT), hemotoxylen-eosin (H&E) staining, and immunohistochemical analysis were conducted. Kruskal-Wallis and Dunn tests with Bonferonni corrrection were applied (p < 0.05).ResultsExpansion and KO supplementation did not cause a statistically significant change in bone mineral density (BMD), bone volume fraction (BV/TV), spesific bone surface (BS/BV) and trabecular thickness (Tb.Th). While the expansion prosedure increased the trabecular seperation (Tb.Sp), KO supplemantation mitigated this effect. The KE group exhibited a statistically significantly increase in trabecular number (Tb.N) compared to the OE group. Although receptor activator of nuclear factor-kappa-Β ligand (RANKL)/osteoprotegerin (OPG) ratios did not show significant differences between groups, the KE and OE groups demonstrated the lowest and highest value, respectively. KE showed a reduced amount of tartrate-resistant acid phosphatase (TRAP) compared to the OE.ConclusionKO positively affected the architecture of the new bone formed in the mid-palatal suture. In this rat model of RME, results support the idea that administering of KO during the expansion period or beginning before the RME procedure may reduce relapse and enhance bone formation within the mid-palatal suture.

Insights into Dietary Different Co-Forms of Lysine and Glutamate on Growth Performance, Muscle Development, Antioxidation and Related Gene Expressions in Juvenile Grass Carp (Ctenopharyngodon idellus).

The study aimed to compare the effects of crystalline L-lysine and L-glutamate (CAA), Lys-Glu dipeptide (KE) on the growth and muscle development of grass carp (Ctenopharyngodon idellus), and related molecular mechanisms. Five experimental diets (CR, 0.5% CAA, 1.5% CAA, 0.5% KE, 1.5% KE) containing Lys and Glu as free (Lys and Glu, CAA) dipeptide (Lys-Glu, KE) forms were prepared, respectively. A total of 450 juvenile grass carp with an initial weight of 10.69 ± 0.07g were randomly assigned to 15 cages, and 5 treatments with 3 replicates of 30 fish each for 61days of feeding. The results showed that the group of 0.5% KE exhibited the best growth performances according to the indicator's weight gain rate (WGR) and specific growth rate (SGR), although no statistically significant occurred among all groups; diet supplemented with 0.5% CAA significantly elevated the condition factor (CF) and viscerasomatic index (VSI) of juvenile grass carp. Diet supplemented with different Lys and Glu co-forms at different levels promoted the muscle amino acid content compared with those of CR group. Comparing with the CR group and other groups, the hardness of 0.5% CAA group significantly increased, and the springiness of 0.5% KE group excelled. Both the muscle fiber diameter and density of 0.5% KE group showed significant difference with those of the CR group, and a negative correlation between them was also observed. To uncover the related molecular mechanism of the differences caused by the different co-forms of Lys and Glu, the effect of different diets on the expressions of protein absorption, muscle quality, and antioxidation-related genes was analyzed. The results suggested that comparing with those of CR group, the dipeptide KE inhibited the expressions of genes associated with protein metabolism, such as AKT, S6K1, and FoxO1a but promoted PCNA expression, while the free style of CAA would improve the FoxO1a expression. Additionally, the muscle development-related genes (MyoD, MyOG, and Myf5) were significantly boosted in CAA co-form groups, and the expressions of fMYHCs were blocked but fMYHCs30 significantly promoted in 0.5% KE group. Finally, the effect of different co-forms of Lys and Glu on muscle antioxidant was examined. The 0.5% CAA diet was verified to increase GPX1a but obstruct Keap1 and GSTP1 expressions, resulting in enhanced SOD activity and reduced MDA levels in plasma. Collectively, the different co-forms of Lys and Glu influenced the growth of juvenile grass carp, and also the muscle development and quality through their different regulation on the protein metabolism, muscle development- and antioxidative-related genes.

Dietary ketone ester attenuates the accretion of adiposity and liver steatosis in mice fed a high-fat, high-sugar diet.

Objective: The ketone diester, R,S-1,3-butanediol diacetoacetate (BD-AcAc2), attenuates the accretion of adiposity and reduces hepatic steatosis in high-fat diet-induced obese mice when carbohydrate energy is removed from the diet to accommodate energy from the ester. Reducing carbohydrate energy is a potential confounder due to the well-known effects of carbohydrate restriction on components of energy balance and metabolism. Therefore, the current investigation was designed to determine whether the addition of BD-AcAc2 to a high-fat, high-sugar diet (with no reduction in carbohydrate energy) would attenuate the accretion of adiposity and markers of hepatic steatosis and inflammation. Methods: Sixteen 11-week-old male C57BL/6J mice were randomized to one of two groups for 9weeks (n = 8 per group): 1) Control (CON, HFHS diet) or 2) Ketone ester (KE, HFHS diet + BD-AcAc2, 25% by kcals). Results: Body weight increased by 56% in CON (27.8 ± 2.5 to 43.4 ± 3.7g, p < 0.001) and by 13% in KE (28.0 ± 0.8 to 31.7 ± 3.1g, p = 0.001). Non-alcoholic fatty liver disease activity scores (NAS) for hepatic steatosis, inflammation, and ballooning were lower in the KE group compared to CON (p < 0.001 for all). Markers of hepatic inflammation [Tnfα (p = 0.036); Mcp1 (p < 0.001)], macrophage content [(Cd68 (p = 0.012)], and collagen deposition and hepatic stellate cell activation [(αSma (p = 0.004); Col1A1 (p < 0.001)] were significantly lower in the KE group compared to CON. Conclusion: These findings extend those of our previous work and show that BD-AcAc2 attenuates the accretion of adiposity and reduces markers of liver steatosis, inflammation, ballooning, and fibrosis in lean mice placed on a HFHS diet where carbohydrate energy was not removed to accommodate energy from addition of the diester.

Effect of Exogenous Acute β-Hydroxybutyrate Administration on Different Modalities of Exercise Performance in Healthy Rats.

A ketone body (β-hydroxybutyrate [β-HB]) is used as an energy source in the peripheral tissues. However, the effects of acute β-HB supplementation on different modalities of exercise performance remain unclear. This study aimed to assess the effects of acute β-HB administration on the exercise performance of rats. In study 1, Sprague-Dawley rats were randomly divided into six groups: endurance exercise (EE + PL and EE + KE), resistance exercise (RE + PL and RE + KE), and high-intensity intermittent exercise (HIIE + PL and HIIE + KE) with placebo (PL) or β-HB salt (KE) administration. In study 2, metabolome analysis using capillary electrophoresis mass spectrometry was performed to profile the effects of β-HB salt administration on HIIE-induced metabolic responses in the skeletal and heart muscles. The maximal carrying capacity (rest for 3 min after each ladder climb, while carrying heavy weights until the rats could not climb) in the RE + KE group was higher than that in the RE + PL group. The maximum number of HIIE sessions (a 20-s swimming session with a 10-s rest between sessions, while bearing a weight equivalent to 16% of body weight) in the HIIE + KE group was higher than that in the HIIE + PL group. However, there was no significant difference in the time to exhaustion at 30 m·min -1 between the EE + PL and the EE + KE groups. Metabolome analysis showed that the overall tricarboxylic acid cycle and creatine phosphate levels in the skeletal muscle were higher in the HIIE + KE group than those in the HIIE + PL group. These results indicate that acute β-HB salt administration may accelerate HIIE and RE performance, and the changes in metabolic responses in the skeletal muscle after β-HB salt administration may be involved in the enhancement of HIIE performance.

Cementless augmented versus cemented Dual Mobility cups: medium-term outcome of case series with a control group

BackgroundPost-operative dislocation and reconstruction of acetabular defects are two challenging topics in revision Total Hip Arthroplasty (rTHA). Cemented Dual Mobility (DM) cups on top of Kerboull Cross and bone graft have been successfully employed to overcome these challenges. The cementless augmented DM cups were recently introduced. In this study medium term results of the augmented cementless DM Coptos cups are reported and compared to the established technique of cemented DM cups and Kerboull plate.Material and methodsThis is a retrospective analysis of data collected on patients who received rTHA using DM cups in the period between June 2015 and September 2020. Two groups of patients were identified. The first group received cementless augmented DM-cups (NOVAE® Coptos TH–SERF) (Coptos TH cup group). The second comparable group who had Kerboull ring (KE ring group) and cemented DM cups (NOVAE® STICK). Demographic data, surgical technique, functional and radiological outcome as well as complications during the follow-up visits are reported.ResultsForty-two patients with a mean age at the time of revision 48.8 ± 13.6 years. 29 patients received Coptos TH DM-cup, while 13 patients had Bone Graft (BG), KE ring and cemented DM cups for acetabular reconstruction. Acetabular defects were Paprosky types IIB and IIC in 31 patients and IIIA and B in 11 patients. The follow-up was 52.8 ± 21 months (mean ± STD); and the mean Harris Hip Score (HHS) at last visit was 91 ± 5. Good stability of all cups was reported. Full integration of the impaction graft was observed in 94% of the Coptos and 92% of the KE groups. One of the Coptos cups was readjusted and one case of single dislocation was recorded in the KE group. None of the DM cups in both groups was revised or awaiting revision.ConclusionCoptos TH cups achieve similar results to the cemented DM on KE ring at the medium term but long term outcome remains to be seen.

The effect of aquous extract of johar leaves (Senna siamea) injection on survival rate and blood profile of snakehead fish (Channa striata)

Aqueous extract of johar leaf contains metabolite compounds such as flavonoids, sponins, tannins, phenols, anthraquinones, anthocyanins, and cardiac glycosides which can be used to substitute commercial antibiotics. The use of aqueous extract of johar leaf has been known to have antibacterial activity in vitro. This study aims to determine the effect of aqueous extract of johar leaves (Senna siamea) injection on survival and blood profile of snakehead fish (Channa striata) in vivo. This research was a laboratory study using a completely randomized design (CRD) with 5 treatments and 3 replications with a total sample of 75 snakehead fish. The fish in KA, KB, KC and KD groups were injected with aqueous extract of johar leaves with concentrations of 10%, 20%, 40%, and 60% respectively, while in KE group the fish was injected with distilled water (control). The parameters of this study were the survival rate and blood profile of snakehead fish. Blood hematology examination included calculation of erythrocyte count, hemoglobin level, and hematocrit percentage, leukocyte count, and thrombocyte count. The research data obtained were analyzed using one-way analysis of variance and followed by Duncan's Multiple Distance test. Injection of aqueous extract of johar leaf did not affect the survival rate of snakehead fish. However, hemoglobin and platelet levels significant decrease in the group given 60% concentration of aqueous extract of johar leaf. It can be concluded that aqueous extract of johar leaf at a concentration of 10%, 20%, 40% is safe to use in snakehead fish.Keywords:Johar leaves extractSnakehead fishBlood profileSurvival rate

Effects of an exogenous ketone ester using multi-omics in skeletal muscle of aging C57BL/6J male mice.

Exogenous ketone ester supplementation provides a means to increase circulating ketone concentrations without the dietary challenges imposed by ketogenic diets. Our group has shown that oral R,S-1,3, butanediol diacetoacetate (BD-AcAc2) consumption results in body weight loss or maintenance with moderate increases in circulating ketones. We have previously shown a diet consisting of 25% BD-AcAc2 can maintain lean body mass (LBM) and induce fat mass (FM) loss in young, healthy male mice, but the underlying mechanisms are still unknown. Therefore, the purpose of this study was to determine if a diet consisting of 25% BD-AcAc2 (ketone ester, KE) would alter body composition, transcriptional regulation, the proteome, and the lipidome of skeletal muscle in aged mice. We hypothesized that the KE group would remain weight stable with improvements in body composition compared to controls, resulting in a healthy aging phenotype. Male C57BL/6J mice (n = 16) were purchased from Jackson Laboratories at 72 weeks of age. After 1 week of acclimation, mice were weighed and randomly assigned to one of two groups (n = 8 per group): control (CON) or KE. A significant group by time interaction was observed for body weight (P < 0.001), with KE fed mice weighing significantly less than CON. FM increased over time in the control group but was unchanged in the KE group. Furthermore, LBM was not different between CON and KE mice despite KE mice weighing less than CON mice. Transcriptional analysis of skeletal muscle identified 6 genes that were significantly higher and 21 genes that were significantly lower in the KE group compared to CON. Lipidomic analysis of skeletal muscle identified no differences between groups for any lipid species, except for fatty acyl chains in triacylglycerol which was 46% lower in the KE group. Proteomics analysis identified 44 proteins that were different between groups, of which 11 were lower and 33 were higher in the KE group compared to CON. In conclusion, 72-week-old male mice consuming the exogenous KE, BD-AcAc2, had lower age-related gains in body weight and FM compared to CON mice. Furthermore, transcriptional and proteomics data suggest a signature in skeletal muscle of KE-treated mice consistent with markers of improved skeletal muscle regeneration, improved electron transport chain utilization, and increased insulin sensitivity.

Association between interindividual variability in training volume and strength gain.

This study aimed to examine the association between interindividual variability in strength changes and in training volume. A total of 26 untrained men completed 4-weeks of isometric knee extension (KE group, n = 12) and hip flexion (HF group, n = 14) training. Each training session comprised four sets of ten isometric contractions, 3-s contractions every 20 s. Training volume, which was defined as impulse during contractions, and maximal voluntary contraction (MVC) torque during KE and HF were evaluated. Based on the magnitude of MVC torque changes, the participants were divided into the high and low responders (n = 13; KE = 6 and HF = 7 per responders). The MVC torque changes (KE, 20.8%; HF, 22.4%) and total training volume did not significantly differ between the two groups. A higher training volume was demonstrated in the low responders than the high responders. The total training volume was positively associated with the MVC torque changes in low responders (r = 0.869%, 95% confidence interval [0.610, 0.960], p < 0.001), but not in high responders [r = 0.229, 95% confidence interval (−0.368, 0.693), p = 0.451], KE or HF group. Results showed that training volume was an important factor in determining the magnitude of strength gains in low responders, and MVC torque could improve by approximately 20% with the use of the study protocol regardless of joint actions involved during training.

Effects of 6-week aerobic exercise on calcium regulation in skeletal muscle of ApoE knockout mice fed by high-fat diet

Objective: To investigate the effects of 6 weeks of aerobic exercise on the sarcoplasmic reticulum calcium regulatory proteins in skeletal muscle of apolipoprotein E (ApoE) knockout mice fed by high-fat diet. Methods: There were a total of twenty five 9-week-old ApoE knockout mice (ApoE knockout mice, ApoE KO), five of which were selected randomly for the maximum running speed test. The running speed would be increased by 1.2 m/min every 3 min after a 5-min duration of initial speed of 4.8 m/min without slope until exhaustion, then the final speed was set as maximal speed, and the test result of the maximum running speed was (27.0±2.4)m/min. The remaining 20 ApoE KO mice were randomly divided into ApoE KO mouse high-fat diet group (KO) and ApoE KO mouse high-fat diet + aerobic exercise group (KE), 10 mice per group. Ten 9-week-old wild-type C57BL/6J mice were used as a blank control group (wild-type, WT). High fat diet composition: fat content was 21% (w/w) and cholesterol content was 1.5% (w/w). Exercise intervention was initiated 1 week after adaptive training in the KE group with an exercise protocol consisting of 40% maximal running speed (10.8 m/min), 40 min/d and a frequency of 3 d/w for a total of 6 weeks. All mice were anesthetized and sacrificed by cardiac puncture then bilateral gastrocnemius muscles were isolated immediately 48 h after the final exercise. Skeletal muscle Ca2+ concentration was detected by visible light colorimetry; the expression levels of RyR, CaM, CaMK Ⅱ, SERCA1 and SERCA2, which are calcium regulated proteins of sarcoplasmic reticulum, in mouse skeletal muscle, was detected by Western blotting. Results: Compared with WT mice, the Ca2+ concentration, the expression levels of the sarcoplasmic reticulum calcium releasing proteins RyR, CaMKⅡ, and the calcium recycling proteins SERCA1 and SERCA2 were decreased significantly in skeletal muscle of the KO mice (P＜0.05, P＜0.01), while the expression of CaM protein did not change. Skeletal muscle Ca2+ concentration and the levels of sarcoplasmic reticulum calcium recycling proteins SERCA1 and SERCA2 were increased significantly (P＜0.05) in KE mice compared with KO mice, but there were no significant differences in the expressions of the sarcoplasmic reticulum calcium release proteins RyR, CaM and CaMK II. Conclusion: High fat diet can reduce the concentration of Ca2+ in skeletal muscle and weaken the release and recovery of sarcoplasmic reticulum calcium in ApoE knockout mice. 6-week aerobic exercise training can significantly increase its Ca2+concentration and promote the recovery of sarcoplasmic reticulum calcium.

Original Knee Fixation Device as a Useful Fixation Method during Prostate Intensity-Modulated Radiation Therapy.

Purpose:The purpose of he study was to reduce setup errors during intensity-modulated radiation therapy (IMRT) with an original knee fixation device (KFD) and evaluate the clinical target volume (CTV) coverage.Methods:Participants were classified into two groups: knee flexion (KF) group (n = 16), wherein participants' knees were fixed in a flexed position using the proposed KFD during planning computed tomography, and knee extension group (KE; n = 15), wherein no KFD was used. We investigated the residual rotational errors and inter-fractional setup errors with or without KFD. Furthermore, inter-fractional margins were calculated using logistic regression analysis, and CTV coverage was evaluated.Results:The residual rotational errors in the yaw and roll directions (P < 0.02) and the inter-fractional error in the anterior-posterior (A-P) direction (P < 0.02) improved significantly in the KF group compared with the KE group. Repeatability was improved for the pitch direction. The inter-fractional margins were 6.68 mm and 4.87 mm in the A-P and superior-inferior (S-I) directions, respectively, in the KF group, representing reductions (mm) of 20.8% and 12.6% compared with the KE group, respectively. The odds ratios for CTV coverage in the KF group compared to the KE group were 2.76 (P < 0.001) and 1.74 (P < 0.05) in the A-P and S-I directions, respectively.Conclusions:The IMRT fixation method using an original KFD improved the residual rotational error in the three directions and the inter-fractional error in the A-P direction, reduced the interfractional margins in the A-P, and S-I directions and improved CTV coverage. Our original KFD may be a useful fixation method during prostate IMRT.

Effects of Bonito Elastin HC on Skin Dryness, Wrinkles, and Pigmentation In Vitro and In Vivo.

We investigated the effects of bonito fish (Katsuwonus pelamis) elastin HC (KE) on skin dryness, wrinkles, and pigmentation in vitro and in vivo. In vitro, we evaluated the expression of mRNA genes and proteins related to skin dryness, wrinkles, and pigmentation. HaCaT and HS27 cells were exposed to ultraviolet B radiation (UVB) (50 mJ/cm2), and B16F10 cells were stimulated with 3-isobutyl-1-methylxanthine (IBMX, 250 μg/mL) for 72 h to induce melanin synthesis. All cells were treated with KE (50-400 μg/mL) for 24 h. We found that KE increased the expression of long-chain base 1, dihydroceramide desaturase 1, elastin, hyaluronan synthase 2, and ceramide synthase 4 mRNA or protein as well as hyaluronic acid and sphingomyelin levels in UVB-irradiated HaCaT cells. Moreover, KE regulated factors related to collagen production, wrinkles, and melanin production in UVB-irradiated HS27 cells and IBMX-stimulated B16F10 cells. In vivo, we evaluated skin hydration and the expression of mRNA genes and proteins in the skin, and conducted morphological observations in SKH-I hairless mice (5-week-old male). The mice were exposed stepwise to UVB and given KE (10, 20, and 30 mg/kg b.w.) for 8 weeks. We found that skin hydration and protein or mRNA expression related to skin moisturization were increased in the KE group. Moreover, KE intake increased factors related to collagen production, wrinkles, and melanin production in UVB-irradiated SKH-I hairless mice. These results suggest that KE may have efficacy for the development of treatments for improving skin health.

Prefabricated ankle-foot orthoses for children with cerebral palsy to overcome spastic drop-foot: does orthotic ankle stiffness matter?

Spastic drop-foot is a common problem in children with cerebral palsy that may lead to tripping and falling. To improve ankle dorsiflexion in swing phase, prefabricated carbon-composite ankle-foot orthoses are commonly prescribed; by increasing ankle stiffness, these orthoses may also improve knee extension in stance. To compare the effect of a stiff vs. flexible prefabricated ankle-foot orthosis on sagittal plane ankle and knee kinematics and kinetics during walking. Cross-sectional, repeated-measures, interventional study. Twenty-seven children and adolescents with cerebral palsy who had drop-foot in swing were included. Gait analysis was conducted under four conditions: barefoot, shod, with a stiff, and with a flexible orthosis. Participants were divided into two groups including children and adolescents who have a flexed knee during stance (KF, N = 12) and without flexed knee during stance (KE, N = 15). Ankle dorsiflexion in swing phase was significantly improved compared with the shod condition by 6.3 degrees (SD = 3.3 degrees) only in the KE group when using the flexible orthosis. For the stiff orthosis, knee extension in stance was significantly increased by 2.4 degrees (SD = 3.3 degrees) in the KE group compared with the shod condition. No significant improvements were observed for the KF group. Further analysis indicated that only seven patients in the KF group with weak ankle plantarflexors improved knee extension while using the stiff orthosis. Our results suggested that in the KE group, the flexible orthosis was best suited for patients with drop-foot without a knee extension deficit. The stiff orthosis was not suitable in this group as it caused a hyperextended knee without improving dorsiflexion in swing phase. Therefore, stiffness should be considered when prefabricated orthoses are prescribed.

The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and improves neuropathology following controlled cortical impact in male rats

ABSTRACT Traumatic brain injury (TBI) is a leading cause of human death and disability with no effective therapy to fully prevent long-term neurological deficits in surviving patients. Ketone ester supplementation is protective in animal models of neurodegeneration, but its efficacy against TBI pathophysiology is unknown. Here, we assessed the neuroprotective effect of the ketone monoester, 3-hydroxybutyl-3-hydroxybutyrate, (KE) in male Sprague Dawley rats (n=32). TBI was induced using the controlled cortical impact (CCI) with Sham animals not receiving the brain impact. KE was administered daily by oral gavage (0.5 ml/kg/day) and provided ad libitum at 0.3% (v/v) in the drinking water. KE supplementation started immediately after TBI and lasted for the duration of the study. Motor and sensory deficits were assessed using the Neurobehavioral Severity Scale-Revised (NSS-R) at four weeks post-injury. The NSS-R total score in CCI + KE (1.2 ± 0.4) was significantly lower than in CCI + water (4.4 ± 0.5). Similarly, the NSS-R motor scores in CCI + KE (0.6 ± 0.7) were significantly lower than CCI + water (2.9 ± 1.5). Although the NSS-R sensory score in the CCI + KE group (0.5 ± 0.2) was significantly lower compared to CCI + water (1.8 ± 0.4), no difference was observed between CCI + water and Sham + water (1.0 ± 0.2) groups. The lesion volume was smaller in the CCI + KE (10 ± 3 mm3) compared to CCI + water (47 ± 11 mm3; p < 0.001). KE significantly decreased Iba1+ stained areas in the cortex and hippocampus, and GFAP+ stained areas in all brain regions analyzed – prefrontal cortex, hippocampus, cortex, amygdala (p < 0.01). In summary, our results indicate that KE can protect against TBI-induced morphological and functional deficits when administered immediately after an insult.

Effect of a self-etching primer containing 4-META and sodium sulfite after phosphoric acid etching on bonding strength of MMA-TBB resin to human enamel

PurposeThe aim of this study was to evaluate the shear bond strength and durability of MMA-TBB resin to human enamel applied a self-etching primer with phosphoric acid etching. MethodsA self-etching primer (Teeth primer, TP) containing 4-methacryloyloxyethyl trimellitate anhydride (4-META) and sodium sulfite and two etchants having different phosphoric acid concentrations (K-etchant gel, KE, 35–45%: Red gel, RG, 20–25%) were used as treatment agent, and MMA-TBB resin was used as luting agent. Enamel surfaces were treated with six methods which were as follow: KE, RG, TP, KE+TP, and RG+TP. After enamel specimens were bonded with MMA-TBB resin and stored in distilled water for 24h, the shear bond strength test was done at 0 thermocycling or 20,000 thermocycling. These results were statistically verified with Steel-Dwass multiple comparisons and Man–Whitney U test. ResultsThe shear bond strength of TP group, KE+TP group, and RG+TP group were significantly higher than KE group and RG group in pre-thermocycling. KE+TP group and RG+TP group were significantly higher than other groups in post-thermocycling. ConclusionsApplying TP with phosphoric acid etching can increased shear bond durability despite difference of phosphoric acid concentrations (35–45% or 20–25%).

In vivo biocompatibility of an interim denture resilient liner containing antifungal drugs

Statement of problemAntifungal agents incorporated into interim denture resilient liners have been suggested as an adjunct treatment for denture stomatitis (DS). However, before applying this protocol to humans, biocompatibility analysis of such drugs in animal models is required. PurposeThe purpose of this animal study was to evaluate the in vivo biocompatibility of an interim resilient liner modified with minimum inhibitory concentrations (MICs) of antifungal drugs for Candida albicans biofilm. Material and methodsSixty Wistar rats were divided into 6 groups (n=5): PC=positive control/no protocol; IOD (intraoral device)=rats using an acrylic resin palatal device (PD); Tru=rats using a PD relined with Trusoft; and Ny (nystatin), Chx (chlorhexidine diacetate), and Ke (ketoconazole) groups=rats using a PD relined with Trusoft + drug MICs. The rats were sacrificed at 7 or 14 days of trial. Histopathological qualitative analysis was performed by comparing photomicrographs of histological sections of the intermolar region. Morphological changes in the epithelium and keratin were quantitatively analyzed by computerized planimetry, and data were analyzed by using 2-way ANOVA and the Tukey HSD test (α=.05). ResultsQuantitative analysis showed that only PD containing Ke significantly decreased the thickness and area of the keratin compared with the other groups (P<.001), which showed no differences between each other (P>.05). These results agreed with those of qualitative analysis. ConclusionsIncorporation of MICs of Ny and Chx in Trusoft did not induce histopathological changes in the rat palatal mucosa, suggesting the in vivo biocompatibility of this DS treatment.

Hypermetabolic Effects of Dietary Ketones are Independent of Changes in Skeletal Muscle Mitochondrial Respiration

Dietary ketone-mediated increases in energy expenditure (EE) have been attributed to increased adipose thermogenesis; however, little is known regarding the contribution of skeletal muscle to the hypermetabolic phenotype. PURPOSE: Determine if dietary ketone esters increase mitochondrial respiration in skeletal muscle. METHODS: Thirty 5-wk old male C57BL/6J mice were placed on an ad libitum high fat diet (HFD) for 10 weeks. Mice were then randomized to one of three groups (n = 10 per group) for an additional 12 weeks: 1) Control (CON, remain on HFD); 2) Ketone Ester (KE, 22% kcal from KE); 3) Pair-fed (PF, pair-fed to KE group). Body composition was measured during the final week of the study by Quantitative Magnetic Resonance (QMR) and EE was examined by indirect calorimetry. Skeletal muscle mitochondrial respiration was measured by high- resolution respirometry in permeabilized muscle fiber bundles. RESULTS: Body weight in the KE group was 27% lower and total adiposity 54% lower than the PF group (p < 0.05 for both) despite comparable energy intake. Differences in body weight and adiposity were attributed to higher resting (REE) and total (TEE) energy expenditure in the KE group (p<0.05). Markers of mitochondrial biogenesis and thermogenesis were increased in brown adipose and a browning phenotype was observed in inguinal white adipose. However, there were no differences in skeletal muscle mitochondrial respiratory capacity between groups. 0.06 CONCLUSIONS: These results provide further support that dietary ketone esters increase brown and white adipose thermogenesis but do not appear to have effects on mitochondrial respiration in skeletal muscle. Supported by: UAB NORC Pilot and Feasibility Award (P30DK056336).

Exogenous ketones lower blood glucose level

Certain disease conditions, involving inflammation and oxidative stress, are accelerated by high blood glucose levels. The safe reduction of blood glucose levels is difficult due to their regulation by powerful homeostatic mechanisms. The ketogenic diet (KD) induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc), β‐hydroxybutyrate (βHB), and acetone in the blood, which serve as alternative metabolic substrates to glucose. However, patient compliance to KD can be low; therefore, exogenous ketones provide an alternative method to establish and maintain elevated blood ketone levels. In this study, we tested the changes in blood glucose and ketone (βHB) levels in response to acute, sub‐chronic and chronic administration of one or more ketogenic compounds in either a post‐exercise or rested state. Rodent models with (WAG/Rij rats, WR and GLUT1Deficiency Syndrome mice, GLUT1D) and without (Sprague Dawley rats, SPD) pathology were tested. Experimental groups included either KD, standard diet with water (control, C) or in combination with the following ketogenic compounds: 1,3 butanediol (BD), beta hydroxybutyrate ketone mineral salt (KS), KS with medium chain triglyceride (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS).In SPD rats without exercise, KD, KS, KE and KSMCT significantly reduced blood glucose levels, compared to control. After exercise blood glucose was significantly lower in the KEMCT group, compared to control. In WR rats KE, KS, KSMCT, KEKS and KEMCT groups had lower blood glucose than control, in both a rested or post‐exercise state. In GLUT1D mice without exercise, KD and KS resulted in significantly lower glucose levels. These results indicate that ketogenic compounds were efficacious in reducing blood glucose levels in and outside the context of exercise.Support or Funding InformationUniversity of South Florida Foundation, GLUT1 Deficiency Syndrome Foundation, National Development Agency of HungaryThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

TOXIC AND IMMUNOTOXIC EVALUATION OF KETAMINE AND/OR ETHANOL IN RATS DURING 28 DAYS

Objective: Studies have shown that ketamine (K) and ethanol (E) have immunomodulatory activity; however, few studies were performed with concomitant treatments. Thus, we evaluated the toxic and immunotoxic effects of this association.Methods: Wistar rats were distributed into four groups (n=8/group), each receiving one of the following treatments, for 28 d: K group (15 mg/kg of ketamine, intraperitoneally); E group [1.0 ml of ethanol 10% (approximately 0,08g/rat), gavage]; KE group, receiving both treatments; and Control (Co) group, receiving only vehicles. On day 29, animals were euthanized for biochemical, hematological, histopathological and immunological evaluation.Results: Although the experimental conditions did not elicit changes on immune parameters, some biochemical alterations were detected in the different groups. Even in the absence of nutritional and histopathological changes, or renal and hepatic markers that could indicate tissue damage, a reduction on alkaline phosphatase levels in rats from K and KE groups was observed. Moreover, changes in lipid markers [cholesterol, triglycerides and high-density lipoproteins (HDL)] were found in the different groups studied, suggesting that K and E could promote a synergic/antagonistic effect.Conclusion: In conclusion, despite biochemical alterations promoted by K and E, associated or not, the doses here employed did not promote immunotoxic effects on rats treated for 28 d. (response to the suggestion in the end of the paper).

Effect of a self-etching primer and phosphoric acid etching on the bond strength of 4-META/MMA-TBB resin to human enamel.

The purpose of this study was to evaluate the shear bond strength and durability of 4-META/MMA-TBB resin to human enamel. A self-etching primer that contained 4-META (Teeth Primer, TP) and 35-45% or 60-65% concentrations of phosphoric acid (K-Etchant Gel, KE, and Super Bond C&B Red Activator, RA) were used as the surface treatment agents. A methyl methacrylate (MMA)-based self-polymerizing resin (Super-Bond C&B) was used as a luting agent. The shear bond strength was determined both pre and post thermocycling. The results were statistically analyzed with a non-parametric procedure. The post-thermocycling shear bond strength of the TP group was significantly higher than that of other groups, and that of the KE group was significantly higher compared with the RA group. These results demonstrated that 4-META was effective. Furthermore, when the degree of tooth demineralization was compared, surface treatment with less demineralization using TP was the most effective treatment.

Effect of low-dose ketamine combined with propofol anesthesia on expression of GluR1 and GABAA R in hippocampus after electroconvulsive therapy in depressed rats

Objective To evaluate the effects of low-dose ketamine combined with propofol anesthesia on the expression of glutamate receptor 1 (GluR1) and γ-aminobutyric acid type A receptor (GABAA R) in hippocampus after electroconvulsive therapy (ECT) in depressed rats.Methods Fifty healthy adult male SpragueDawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.The depressed model was induced by chronic unpredictable mild stress (CUMS).The mentally depressed rats were randomly divided into 5 groups (n =10 each):depression group (group D),ECT group,ketamine + ECT group (group KE),propofol + ECTgroup (group PE) and ketamine + propofol + ECT group (group KPE).Group ECT received ECT once a day for 7 consecutive days after intraperitoneal injection of normal saline 8 ml/kg.KE,PEK and KPE groups received ECT once a day for 7 consecutive days after intraperitoneal injection of ketamine 10 mg/kg,propofol 100 mg/kg,and ketamine 10 mg/kg + propofol 80 mg/kg,respectively.Sucrose fluid consumption was performed before CUMS,at 1 day after CUMS and at 1 day after ECT.The rats were sacrificed and hippocampi were removed for determination of the expression of GluR1 and GABAA R (by immuno-histochemistry).The GluR1/GABAA R ratio was calculated.Results Compared with group D,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA Rratio was increased in the other four groups,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in ECT,PE and KPE groups (P ＜ 0.05).Compared with ECT group,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GABAA R and GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group,the expression of GluR1 and GABAA R in hippocampal CA1 and CA3 regions was up-regulated in KE group,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in PE group (P ＜ 0.05).Compared with group PE,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 and GABAAR in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group (P ＜ 0.05).Conclusion The mechanism by which low-dose ketamine combined with propofol enhances the efficacy of ECT in depressed rats may be related to better regulation of the balance between hippocampal GluR1 and GABAA R. Key words: Depression; Ketamine ; Propofol ; Electroconvulsive therapy ; Receptors, AMPA ; Receptors, GABA-A; Hippocampus