DA Group Research Articles

Effects of biogenic amines on the immune response and immunoregulation mechanism in hemocytes of Litopenaeus vannamei in vitro

The effects of three biogenic amines (DA, NE and 5-HT) on the immune signaling pathway and immune response of hemocytes in shrimp were investigated through in vitro experiments. The results showed that the G protein effectors (AC, PLC), the second messengers (cAMP, DAG), Calmodulin (CaM) and protein kinases (PKA, PKC) of DA and NE groups shared a similar trend in which all intracellular signaling factors increased significantly and reached the maximum at 3 h. The concentrations of AC, cAMP and PKA in 5-HT groups decreased significantly compared with the control group, while the concentrations of PLC, CaM, DAG and PKC in 5-HT groups increased markedly. The immune parameters such as total hemocyte count (THC), cell viability, antibacterial activity and bacteriolytic activity, as well as prophenoloxidase (proPO) activity in three biogenic amines groups decreased significantly, while the phenoloxidase (PO) activity increased significantly. The phagocytic activity in DA and NE groups decreased significantly, while that in 5-HT groups increased markedly and reached the highest level at 1 h. Among these three biogenic amines, DA showed the strongest effect on the immune activity of the hemocytes, whereas 5-HT had the least effect. In addition, we speculated that DA and NE might regulate phagocytosis by activating intracellular AC-cAMP-PKA pathway while 5-HT might inhibit intracellular AC-cAMP-PKA pathway. Moreover, the activation of proPO system might be related to PLC-DAG-PKC and PLC-CaM pathway.

Tissue-Engineered Decellularized Allografts for Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) reconstruction with allografts is limited by high immunogenicity, poor cellularization, and delayed tendon-bone healing. Decellularized tendons (DAs) have been used as bioscaffolds to reconstruct ligaments with variable success. In the study, four kinds of decellularized allogeneic hamstring tendons were prepared and their microstructure and cytocompatibility were examined in vitro. The results showed that decellularized allografts neutralized by 5% calcium bicarbonate had typical reticular and porous microstructures with optical cytocompatibility. Tissue-engineering decellularized allografts (TEDAs) were prepared with the selected decellularized allografts and tendon stem/progenitor cells and used for ACL reconstruction in a rabbit model. Histological staining showed that the TEDAs promoted cellular infiltration and new vessel formation significantly and improved tendon-bone healing moderately compared to decellularized allografts. Better macroscopic scores and biomechanical results were observed in TEDA groups, but there were no significant differences between DA and TEDA groups at months 1, 2, and 3 postoperatively. Immunohistochemical data showed that the tissue-engineering decellularized allografts enhanced the expression of collagen I at each timepoint and collagen III at months 1 and 2. ELISA analysis showed that the tissue-engineering decellularized allografts reduced the secretion of IgE and IL-1β within 1 month and promoted the secretion of IL-2, IL-4, IL-10, and IL-17 after 1 month. The results showed that tissue-engineering decellularized allografts strengthened intra-articular graft remodeling significantly and provided moderate improvements in tendon-bone healing by creating more suitable immune responses than decellularized allografts. The study revealed that tissue-engineering decellularized allografts as a promising option for ACL reconstruction could achieve more favorable outcomes.

Comparison of Sedation with Dexmedetomidine Alfentanil Versus Ketamine-Alfentanil in Patients Undergoing Closed Reduction of Nasal Fractures.

ObjectivesTo compare the sedative effects of dexmedetomidine alfentanil versus ketamine-alfentanil in patients undergoing closed reduction of nasal fractures on the basis of intraoperative hemodynamic changes, satisfaction of patients and surgeons, and the adverse effects.MethodsSixty patients with ASA class 1 or 2 were randomized to either of two groups, a dexmedetomidine alfentanil group (DA group; n = 30) or a ketamine-alfentanil group (KA group; n = 30). Hemodynamic parameters, oxygenation status, adverse events, the satisfaction of patients and surgeons, and postoperative pain scores by visual analog scale (VAS) were recorded at specific time intervals during the trial.ResultsSystolic blood pressure was significantly lower in the DA group than in the KA group from T1 min to T15 min. The duration of the recovery ward stay was longer in the DA group; however, two groups were similar in terms of total anesthesia time and awakening time. Likewise, two groups were similar in terms of the patient and surgeon’s satisfaction, pain scores, and the occurrence of adverse effects.ConclusionsBoth sedation methods were safely performed, and dexmedetomidine-alfentanil is as effective as ketamine-alfentanil in patients undergoing short-term operations such as nasal fracture corrections.

The prevalence of small-bowel polyps on video capsule endoscopy in patients with sporadic duodenal or ampullary adenomas

Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30mm (range, 10-80mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P=.002)). Advanced colonic adenoma (high-grade dysplasia, >10mm, villous histology) were found in 18% of the DA group and 5% of the control group (P=.018). Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.).

Effect Of Aerobic Exercise On Cardiac Diastolic Dysfunction: Role Of Heat Shock Protein 27

PURPOSE: To evaluate the role of heat shock protein 27 (HSP27) in the effect of aerobic exercise on cardiac diastolic dysfunction in type 2 diabetic rats. METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups: control (C), aerobic exercise (A), diabetes (D), and diabetes plus aerobic exercise (DA). Type 2 diabetes was induced by feeding with a high-fat high-sugar diet for 7 weeks followed by a single intraperitoneal injection of streptozotocin (30mg/kg) in the rats. Aerobic exercise was performed on a rodent treadmill at 21m/min for 60 min, 5 days per week for 8 weeks. Metabolic factors, such as fasting blood glucose (FBG), triglycerides (TG), cholesterol (CHOL) and lipoproteins, were determined by a standard procedure. Cardiac structure and function, such as left ventricular diastolic upper diameter (LVIDd), left ventricular diastolic terminal volume (EDV) and ejection fraction (EF), were measured using echocardiography. Myocardial HSP27 protein expression and phosphorylation were determined using western blot, and myocardial HSP27-titin colocalization were determined using double immunofluorescence. Two-way ANOVAs with post-hoc tests were used to assess differences between groups. RESULTS: No pathological changes were observed in the myocardial structure in all four groups. Compared to the C group, the D group had significantly higher levels of FBG, TG, and CHOL (all p<0.01), and significantly lower LVIDd and EDV (both p<0.01). Compared to the D group, the DA group had significantly lower levels of FBG, TG, and CHOL (all p<0.01) and significantly higher LVIDd and EDV (both p<0.05). Interestingly, compared to the C group, the D group showed significantly lower myocardial HSP27 phosphorylation and HSP27-titin colocalization (both p<0.05), while the DA group showed significantly higher myocardial HSP27 protein expression and phosphorylation, and HSP27-titin colocalization than the D group (all p<0.01). CONCLUSION: Decreases in myocardial HSP27 phosphorylation and HSP27-titin colocalization are likely involved in early diastolic dysfunction in diabetic rats. Increased HSP27 phosphorylation and titin colocalization may be an important mechanism by which aerobic exercise restores diastolic function in diabetic rats.

Protective effects of extracts of lichen Dirinaria consimilis (Stirton) D.D. Awasthi in bifenthrin- and diazinon-induced oxidative stress in rat erythrocytes in vitro

The intoxication of insecticides such as bifenthrin and diazinon has been reported to generate free radicals, and thereby alter the antioxidant defense system in erythrocytes. The present study is aimed to investigate the protective effects of acetone (DA) and methanolic (DM) extracts of lichen Dirinaria consimilis against bifenthrin and diazinon toxicity in rats’ erythrocytes in vitro. Rats’ erythrocytes were exposed to bifenthrin and diazinon, individually and also in combination with DA or DM at 1 ppm for 3 h at 37 ˚C. By using spectrophotometric methods, all the samples were estimated for changes in hemoglobin (Hb) concentration, malondialdehyde (MDA) levels, and enzyme [Superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferases (GST)] activities. The outcomes showed that both the insecticides were highly toxic to rats’ erythrocytes. Among all groups, both the insecticides and DA exposed groups showed very low levels of MDA content, and GST activity in rats’ erythrocytes, when compared to the control. Besides, DA groups pretreated with both insecticides showed significant improvement of total Hb concentration, SOD, and CAT activities, with respect to the control. Hence, the present results indicate that the extracts of D. consimilis act as an antioxidant agent that reduces oxidative stress burden in insecticides toxicity.

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes

PurposeTo investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation.MethodsStudy animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively.ResultsThe urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL-18 and IL-1β in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder.ConclusionsThis study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.

Eye of Stranger: Evaluate of Chorioretinal Microvascular Networks on Ventricular Assist Device

To evaluate microvascular architecture of eyes in cases with continuous-flow (CF) left ventricular assist device (LVAD) to find out the possible effects of LVADs over blood supply of end organs. For each study eye, high resolution scans of chorioretinal microvascular networks were captured via optical coherence tomography angiography (OCTA); which is a novel noninvasive, dye free, three dimensional angiography technique using the movement of red blood cells within chorioretinal capillaries against static ocular tissue as an intrinsic contrast to generate flow imaging. Eyes with any ocular diseases and those depicted low quality OCTA images according to optic media opacities were excluded. Study group included the eyes of LVAD cases with a minimum two years of follow-up. Demographics and OCTA findings were recorded and statistically analyzed to find out possible alterations of retinal and choroidal blood supply between LVAD cases and the controls. Comparison of OCTA findings between patients with LVAD implantation by thoracotomy with anastomosis of the outflow graft to the descending aorta (DA group) and those with the standard approach (AA group) was the secondary end point. Twenty three eyes of 13 LVAD implanted cases and 21 eyes of 12 healthy controls were included. There was no statistical difference in age and gender distribution between two groups (p=0.945 and p=0.601, respectively). Mean central foveal thickness (CFT) and choroidal thickness (CT) were 228.0±17.0 µm and 314.5±50.8 µm in study group; whereas they were 223.0±13.0 µm and 256.1±36.1 µm in the controls (p=0.287 and p<0.001, respectively). No statistical significance was found in total and four quadrant OCTA findings of superficial and deep retinal capillary plexuses as well as choriocapillaris between two groups (p>0.05 for all). Among cases with LVAD implantation, any statistically significant difference was also not found in OCTA scores between DA and AA subgroups which comprised of 6 and 17 eyes, respectively. Increased CT was found in patients underwent CF LVADs possibly due to raised capillary pressure in such cases. Except for CT measurements, similar scores of studied OCTA parameters between LVAD cases and the controls revealed that CF LVADs have not any negative impact over end organ blood supply in late term without any respect to being in either DA or AA subgroup.

A Comparison Study of Dynamic Assessment and Nondynamic Assessment on EFL Chinese Learners' Speaking Performance: Transfer of Learning

Abstract One goal of language instruction is to support students’ ability to transfer their learning or apply what they have learned in school to another setting. A common problem arises when the expected transfer does not take place, and follow-up assessments are unable to reveal where the student has had difficulty learning the language in such a way that they can apply it in other settings. Dynamic assessment (henceforth, DA) rooted in Vygotsky’s sociocultural theory has explained the importance of learning transfer or transcendence. Defined as the change in an individual’s cognitive knowledge that is applicable to other situations, transcendence supports the individual to move beyond the “here-and-now” demands of a given activity. DA differs from traditional nondynamic assessment (henceforth, NDA) in that DA makes it possible for teachers to make teaching recommendations based on their assessment of a learner’s developmental potential. The present study aims at investigating the differences between applying dynamic assessment and nondynamic assessment to EFL Chinese learners’ speaking performance and examining their transfer effect. Data included 119 first-year college students’ performance on integrated speaking tasks and records of the teacher’s interactive support and learners’ responses to the mediation. Results indicated that DA outperformed the NDA group in terms of supporting improvements in college students’ speaking performance. The interactive mediation provided through DA assisted advanced learners’ content development in speaking and assisted beginning learners’ control of grammatical structures. More importantly, the learning effect on the DA group did not fade away over time. Both beginning and advanced level learners performed better transcendence after receiving DA intervention. This study contributes to the literature in that few studies have examined whether DA assists speaking performance at the tertiary level in comparison to nondynamic assessment approaches.

Effects of ATRA on diabetic rats with renal ischemia-reperfusion injury.

Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats.Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope.Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group.Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.

Productivity, Nutrient Digestibility, Nitrogen Retention, and Meat Quality in Rabbits Fed Diets Supplemented with Sida hermaphrodita.

Simple SummaryAlfalfa is an important forage crop in rabbit nutrition. Despite the numerous advantages of alfalfa, efforts have been made to find its potential substitutes. Virginia fanpetals (Sida hermaphrodita), is yet another potential substitute for alfalfa in animal diets. The aim of this study was to evaluate the efficacy of dehydrated Virginia fanpetals meal as a substitute for dehydrated alfalfa meal in rabbit diets. The results of this study indicated that Virginia fanpetals meal can be included in rabbit diets at up to 20% as a substitute for alfalfa without compromising the production performance of animals, nutrient digestibility, nitrogen retention, carcass quality, or meat quality parameters.Alfalfa (Medicago sativa) is an important forage crop in rabbit nutrition. Despite the numerous advantages of alfalfa, efforts have been made to find its potential substitutes. The aim of this study was to evaluate the efficacy of Sida hermaphrodita meal as a substitute for alfalfa meal in rabbit diets. The experiment was performed on 90 New Zealand White rabbits divided into three groups. DA group was fed a diet containing 20% dehydrated alfalfa. In the DA/DS group, rabbits received a diet containing 10% dehydrated alfalfa and 10% dehydrated Sida. The diet administered to the DS group contained 20% dehydrated Sida. The results of this study indicate that the dietary supplementation with Sida contributed to an increase in the final body weight of rabbits and improved the feed-conversion ratio. Experimental diets had no influence on nutrient digestibility, nitrogen retention, and selected carcass characteristics of rabbits, except for the proportion of the hind part. The content of dry matter, total protein, and monounsaturated fatty acids in the hind leg muscles of rabbits was higher in the DA group than in the experimental groups. The concentrations of saturated fatty acids were higher in the tissues of animals fed diets supplemented with Sida.

Anterior versus posterior approach total hip arthroplasty: patient-reported and functional outcomes in the early postoperative period.

Direct anterior approach total hip arthroplasty (DA THA) has been reported to improve early outcomes compared to posterior approach THA up to 6 weeks postoperatively. Limited weekly outcomes data are available prior to 6 weeks. We evaluate outcomes including when patients first drive a car, leave home, and discontinue their assist device. Patients undergoing THA for primary osteoarthritis were prospectively enrolled. Outcomes data were collected preoperatively and postoperatively at weekly intervals for 6 weeks. 111 patients (55 DA and 56 posterior approach) were enrolled. There was no significant difference (p > 0.05) in pre-surgical Patient-Reported Outcomes Measurement Information System (PROMIS) scores or modified Harris Hip Score (mHHS).Postoperatively, the DA THA group had decreased length of stay (p = 0.0002) and increased distance walked on postoperative day 1 and 2 (p = 0.011, p = 0.0004). The DA group had lower pain scores (p < 0.05) and required less day 1 and total narcotics (p = 0.029, p = 0.01). The DA cohort had improved PROMIS Physical Function scores and mHHS up to 5 weeks postoperatively. DA patients discontinued their assistive device 8 days earlier (p = 0.01), left home 3 days earlier (p = 0.001), and drove a car 5 days earlier (p = 0.01). Patients undergoing DA THA discontinued their assistive device, left their home, and drove a car sooner than posterior approach patients. We found improvement in physical function with DA, and it persisted up to 5 weeks postoperatively. Furthermore, DA patients had significantly shorter length of stay, improved mobilisation, decreased narcotic requirements and improved inpatient pain scores compared to posterior approach THA. Future randomised controlled study should be performed to minimise the biases inherent in this study methodology and confirm the results.

Anatomy of the organic carbon related to the Miocene syn-rift dysoxia of the Rudeis Formation based on foraminiferal indicators and palynofacies analysis in the Gulf of Suez, Egypt

Abstract The syn-rift deposits from the Gulf of Suez witness different episodes of anoxia and dysoxia conditions. In many areas, the sediments of Rudeis Formation that represent the deposition in the time of maximum rift subsidence are considered as the principal organically rich and oil prone sources, while in other areas they are not. These differences are attributed to relative positions to the location of the syn-rift dysoxia and amounts of the carbon flux during active paleoproductivity time. In the present study, an extensive analysis of the syn-rift dysoxia and paleoproductivity during the Miocene is conducted in Burdigalian Rudeis Formation in Ramadan-1 well to determine their influence on the accumulation of organic carbon. The analysis depends on the statistical investigation of the benthic foraminiferal assemblages. The foraminiferal assemblages are discriminated into two biofacies in R-mode (suboxic and dysoxic) and three biotopes in Q-mode (suboxic (S), dysoxic DA and DB sample groups). The sediments are divided into three stratigraphic sequences. Five oxygen minimum zones are determined at the extreme oxygen depletion intervals and they are defined by suboxic (S) and dysoxic (DA) sample groups in descendent order of oxygen depletion intensity and mostly coincide with the high sea levels. The distribution of the organic matter showed large enrichment with partial fluorescence amorphous organic matter indicating kerogen type II in the three biotopes as clarified from palynofacies analysis. The organic carbon enrichment from the studied samples ranged from fair to very good (0.51 and 2.38 wt%) and the relatively larger enrichments are found to be correlated with dysoxic sample group (DA) of intermediate oxygen depletion. The pyrolysis gas chromatography (PGC) specifies the algal rich Type I kerogen that deposited in oxygen depleted marine environment. The mathematical calculation of the paleoproductivity (oligotrophic to eutrophic range 106–352 gCM−2yr−1), carbon flux (13.77 and 36.19 gCm−2yr−1) indicates that higher levels of organic productivity are correlated with dysoxic sample group (DA). The larger organic carbon values are found in the Rudeis Formation when the dysoxic conditions from the deeper topographic lows extend to the higher tectonic position of Ramadan-1 well during the sea level rise that furthermore enhances the paleoproductivity.

Direct anterior versus posterolateral approach for bipolar hip hemiarthroplasty in femoral neck fractures: a prospective randomised study.

Femoral neck fractures are a major problem in orthopaedic practice, having a huge impact on society, and involving a large number of elderly patients for whom early recovery is paramount. Thus, the aim of this study was to compare 2 surgical approaches, direct anterior (DA group) versus posterolateral (PL group), used for bipolar hip hemiarthroplasty (BHA) with femoral neck fractures in order to assess pain recovery after surgery. Our hypothesis was that early pain recovery would be faster in the DA group. 100 patients were randomised to surgery using either a DA group or PL group approach, and were then followed up for 6 months. Surgical time, intra- and postoperative complications were recorded for each patient. The main outcome, pain, was recorded using an NRS scale at 3 days, 1, 3 and 6 months after surgery. At the same time, patient status was evaluated using Activities of Daily Living and Cumulated Ambulation Score scales. Surgical time was longer in the DA group (p < 0.0001). Pain perception at 3 days and at 1 month after surgery was significantly lower in DA group patients (p < 0.0001). The results of the other scales were comparable in the 2 groups (at 3 days, 1 and 3 months after surgery). The DA approach offers a significant advantage in terms of pain perception up to 1 month after the operation. Early recovery in terms of pain perception is an important finding. Future studies should explore whether this early pain reduction could translate into a faster rehabilitation programme for an earlier recovery of full function.Clinical trial registration: Protocol 423/CE; Study n. CE 41/15.

Euterpe oleracea Mart. (Açai) Supplementation Attenuates Acute Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased β-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.

PB1724 FLT3 MUTATED AML: THE ROLE OF CLADRIBINE AND MIDOSTAURIN ADDED TO THE STANDARD INTENSIVE CHEMOTHERAPY ‐ SINGLE CENTRE EXPERIENCE FROM UMC LJUBLJANA, SLOVENIA

Background:The FLT3 ITD mutation in a patient with acute myeloid leukemia (AML) is associated with a poor outcome. Midostaurin is the first multikinase inhibitor approved for the treatment of adults with newly diagnosed FLT3 positive AML. The drug has been available in Slovenia from July 2017 and used in all eligible FLT3 patients. Furthermore, following encouraging results shown by the Polish Adult Leukemia Group, we have been adding cladribine to standard combination DA3+7 induction (namely DAC) for all AML patients aged 60 years or less since 2014.Aims:To compare the outcome of FLT3 positive AML patients treated with DA3+7 or DAC with further addition of midostaurin.Methods:We retrospectivelly analyzed all consecutive FLT3 positive AML patients, aged 60 years or less, treated with intensive chemotherapy between years 2012‐2018. Bone marrow (or in some cases peripheral blood) RNA was used for FLT3 mutation detection. FLT3 ITD mutation was detected by reverse transcription PCR (RT‐PCR) and gel electrophoresis analysis. FLT3 D836 mutation detection was carried out by RT‐PCR and Restriction Fragment Length Polymorphism technique using restriction enzyme EcoRV. From 01/2012 – 04/2014 DA3 + 7 was used, while from 05/2014 – 12/2018 DAC (addition of 5 mg/m2 of cladribine in a 3‐hour infusion on days 1‐5 to DA3 + 7) was used for all AML patients aged 60 years or less eligible for intensive chemotherapy. Remission was assessed by bone marrow aspiration in the aplastic phase and before the first consolidation therapy. Consolidation treatment was intermediate or high dose cytosar. Midostaurin was added according to indication no later than in the first consolidation phase (2x50 mg from day 8‐21). All patients with FLT3 ITD mutation and available donor were transplanted. Patients who had not achieved remission after induction chemotherapy proceeded with rescue chemotherapy and allogeneic transplantation. Patients who were not transplanted continued maintenance treatment with midostaurin 2x50 mg continuously for one year.Results:There were 39 FLT3 positive AML patients aged 60 years or less who were treated with intensive chemotherapy in the period 2012‐2018: 16 with DA3 + 7 and 23 with DAC. There was no difference between the baseline characteristics between the groups (Table 1). Remission after induction was achieved in 9/16 patients in the DA group (1 patient was treated with midostaurin during induction) and 19/23 in the DAC group (5 patients received midostaurin during the induction), p = 0,072. Survival was significantly better in the DAC group in which overall 12/23 patients were treated with midostaurin compared to DA3 + 7 where only 1 patient was treated with midostaurin; p = 0,028. The proportion of patients with allogeneic transplant was similar (7/16 in the DA and 11/23 in the DAC group; p = 0,802). When comparing patients with or without midostaurin treatment the survival was significantly better in patients treated with midostaurin (p = 0,005), however, the median observation time was only 11 months. The addition of midostaurin to DAC did not increase toxicity.Summary/Conclusion:Addition of cladribine and midostaurin to standard DA3 + 7 improved survival in FLT3 positive AML patients. No new safety signals were noted in patients receiving DAC + midostaurin. Further follow‐up is required to evaluate influence of midostaurin in combination with DAC induction chemotherapy on progression free survival and overall survival.image

Three-Dimensional In Vivo Analysis of Malunited Distal Radius Fractures With Restricted Forearm Rotation.

Malunited distal radius fractures (DRFs) occasionally restrict forearm rotation, but the underlying pathology remains unclear. We aimed to elucidate the mechanism of rotational restriction by retrospective analysis of 23 patients with unilateral malunited DRFs who presented restricted forearm rotation. We conducted computed tomography during forearm rotation on both sides. Three-dimensional (3D) bone surface models of the forearm were created, and 3D deformity of the distal radius, translation of the distal radius relative to the ulna, distal radioulnar joint (DRUJ) contact area, and estimated path length (EPL) of distal radioulnar ligaments (DRUL) during forearm rotation were evaluated. In total, 18 patients had dorsal angular deformities (DA group) and five had volar angular deformities (VA group). In the DA group, the closest point between the distal radius and ulna on DRUJ was displaced to the volar side during supination and pronation (p < 0.001); DRUJ contact area was not significantly different between the DA and normal groups. In bone-ligament model simulation, the EPL of dorsal DRUL was longer in the DA group than in the normal group (p < 0.001); opposite phenomena were observed in the VA group. In the DA group, translation of the distal radius in a volar direction relative to the ulna during pronation was impaired presumably due to dorsal DRUL tightness. Anatomical normal reduction of the distal radius by corrective osteotomy may improve forearm rotation by improving triangular fibrocartilage complex tightness and normalizing translation of the distal radius relative to the ulna. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1881-1891, 2019.

Short-term dexamethasone plus acetylsalicylic acid treatment during in vitro fertilization procedure.

Embryo implantation represents the major limiting step during in vitro fertilization (IVF) procedure. Immu- nological and coagulation abnormalities were shown to have a substantial part in multifactorial etiology of IVF failure. We aimed to investigate the effect of short-term low-dose dexamethasone plus acetylsalicylic acid (ASA) treatment, starting at the time of embryo transfer, on the implantation and clinical pregnancy rates in general IVF population. Out of 233 consecutive patients undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles 64 received an adjuvant treatment consisting of dexamethasone (0.5 mg/day) plus ASA (100 mg/day) (DA group), starting on the day of embryo transfer. Patients not receiving these medications comprised a control group. Significantly more patients in DA group had positive ß-hCG values than controls (59.38% vs. 37.67%, p = 0.004) (OR = 2.42, 95% CI: 1.33-4.41). Implantation rate was 26.53% in DA group and 15.92% in controls (p = 0.0294). Clinical preg- nancy rate per started cycle was higher in DA group (43.59%) than controls (28.92%), but the difference was not significant (p = 0.0879; OR = 1.99, 95% CI: 0.89-4.41). Our study shows a potential benefit of dexamethasone plus ASA adjuvant treatment in females undergoing IVF/ICSI procedure. As these results show improvement of IVF outcome, a greater number of patients undergoing this type and regime of adjuvant treatment should be investigated.

Mechanism of dexmedetomidine-induced reduction of acute visceral pain in rats: relationship between alpha2 adrenergic receptors and expression of Nav1.8 in dorsal root ganglion neurons

Objective To evaluate the relationship between alpha2 adrenergic receptors and expression of Nav1.8 in dorsal root ganglion(DRG)neurons, and to illuminate the mechanism of dexmedetomidine-induced reduction of acute visceral pain in rats. Methods Thirty-two clean-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), acute visceral pain group (group VP), dexmedetomidine group (group D), and dexmedetomidine plus atipamezole group (group DA). In VP, D and DA groups, 10-3 mmol/L capsaicin 1.3 ml was injected into the rectum at a dose of 10-3 mmol/L to establish the acute visceral pain model, while the equal volume of normal saline was given instead in group C. Atipamezole 1 mg/kg was subcutaneously injected through the back of the neck at 20 min before establishing the model in group DA.Dexmedetomidine 10 μg/kg was injected through the tail vein at 15 min before establishing the model in D and DA groups, while the equal volume of normal saline was given instead at the correspording time points in C and VP groups.The visceral pain behavior score was recorded at 1 h after establishing the model.The animals were then sacrificed, and DRGs of the lumbar segment (L3-6) were removed for determination of the number of Nav1.8 positive DRG neurons (by immunohistochemistry) and expression of Nav1.8 mRNA (by quantitative real-time polymerase chain reaction). Results Compared with group C, the visceral behavior scores and the number of Nav1.8 positive DRG neurons were significantly increased, and the expression of Nav1.8 mRNA was up-regulated in VP, D and DA groups (P<0.05). Compared with group VP, the visceral behavior score and the number of Nav1.8 positive DRG neurons were significantly decreased, and the expression of Nav1.8 mRNA was down-regulated in D and DA groups (P<0.05). Compared with group D, the visceral behavior scores and the number of Nav1.8 positive DRG neurons were significantly increased, and the expression of Nav1.8 mRNA was up-regulated in group DA (P<0.05). Conclusion The mechanism by which dexmedetomidine reduces acute visceral pain is related to activating alpha2 adrenergic receptors and to down-regulating the expression of Nav1.8 in DRG neurons of rats. Key words: Dexmedetomidine; Visceral pain; Receptors, adrenergic, alpha-2; Ganglia, spinal; NAV1.8 voltage-gated sodium channel

Surface Topography, Gloss and Flexural Strength of Pressable Ceramic After Finishing-Polishing Protocols.

This study evaluated the effect of different finishing-polishing protocols on surface roughness, gloss, morphology and biaxial flexural strength of pressable fluorapatite glass ceramic. Thirty ceramic discs (12x1 mm) were produced and divided into five groups (n=6): CT: control (glaze); DA: fine grit diamond bur; DG: DA + new glaze layer; DP: DA + felt disk with fine grit diamond paste; DK: DA+ sequential polishing with silicon abrasive instruments, goat hair brush and cotton wheel. The specimens were analyzed for surface roughness (Ra) under profilometry and atomic force microscopy (AFM). Gloss was measured with spectrophotometry and micromorphology with scanning electron microscopy (SEM). Flexural strength was assessed by biaxial flexural strength test. Data were analyzed using one-way ANOVA and Tukey's post hoc test (a=0.05). DK showed the lowest surface roughness values and DA presented the highest in the perfilometer analysis. No significant differences were observed in the AFM for the CT, DG and DK groups, which presented the lower surface roughness; DA and DP had the higher Ra values. The DA, DP and CT showed the lowest surface gloss values, and the reflectance was significantly different from those observed for DK and DG groups. SEM analysis revealed the smoothest surface for DK group, followed by DG and CT groups; DA and DP groups exhibited variable degrees of surface irregularities. No significant differences were observed among groups for the biaxial flexural strength. The polishing protocol used in DK group can be a good alternative for chairside finishing of adjusted pressable fluorapatite glass ceramic surfaces.