TAT Group Research Articles

Role of Transanastomotic Feeding Tube versus Early Gastric Feeding in Postoperative Duodenal Surgery

Background: Postoperative enteral feeding in congenital duodenal obstruction is usually delayed due to dilated atonic duodenum. The trans-anastomotic tube feeding (TAT) has been proposed to be more effective than early gastric feeding in the role of supporting “Enhanced recovery after surgery concept”. Objective: Comparing time to feeding among patients using TAT, early gastric feeding, and traditional delayed gastric feeding. Materials and Methods: Comparing postoperative enteric feeding via TAT (group A: n=7) and gastric feeding (group B: n=6) — prospective data collected from 2015 to 2020 — to traditional gastric feeding (group C: n=17) that is retrospective data from 2008 to 2015, in neonates with congenital duodenal obstruction. Results: TAT and early gastric (OG) feedings had provided earlier enteral feeding compared to traditional practice (p<0.001). The early gastric feeding was faster full fed than TAT on the earlier postoperative date with median (IQR) = 11 (10, 11) and 16 (13, 23) respectively. However, all 3 groups had the same timing of gastric full feeding (median (IQR): A=8 (5, 11); B=7 (4, 7); C=9 (5, 10)), p=0.772. Even not significant, the early gastric feeding group provided the shorter time of hospital stay and TPN administration. Conclusion: The early OG feeding is feasible for early postoperative feeding comparable to TAT feeding and applicable in cases beware of TAT-related complications. Postoperative gastric function recovery is not related to the pre- or post-anastomotic feeding. Keywords: Duodenal atresia; Duodenal stenosis; Neonatal duodenal obstruction; Trans-anastomotic feeding tube; Enteral feeding; ERAS

Discovery of dual targeting PEGylated BG-P1600-TAT to norepinephrine transporter (NET) and thyrointegrin αvβ3 in the treatment of neuroblastoma

Polymer-drug conjugates are growing in interest as novel anticancer agents for targeted cancer therapy. The aim of this study was to synthesize a poly(ethylene glycol) (PEG) conjugated anticancer drug for neuroblastoma, which is the most common extracranial solid tumor of childhood and the deadliest tumor of infancy. In our previous studies, we designed and synthesized a dual targeting agent using benzylguanidine (BG) conjugated with the high affinity thyrointegrin αvβ3 antagonist TriAzole Tetraiodothyroacetic acid (TAT) via non-cleavable bonding to PEG400 to make BG-P400-TAT and its derivatives as agents against neuroblastoma. Here, we improved the pharmacodynamic properties and increased the solubility by changing the polymer length to 1600 molecular weight. The TAT group, which acts as an integrin αvβ3 antagonist, and the BG group, which can be taken up by neuroblastoma cells through the norepinephrine transporter (NET) system, are conjugated to PEG1600 to make BG-PEG1600-TAT. The binding affinity of BG-PEG1600-TAT was 40-fold higher to integrin αvβ3 versus BG-P400-TAT and was associated with greater anticancer activities against neuroblastoma cells (SK-N-F1 and SKNAS) implanted in SCID mice along with broad spectrum anti-angiogenesis activities versus the FDA approved anti-Vascular Endothelial Growth Factor (VEGF) monoclonal antibody Avastin (bevacizumab). In conclusion, our novel dual targeting of NET and αvβ3 receptor antagonist, BG-P1600-TAT demonstrated broad spectrum anti-angiogenesis and anti-cancer activities in suppressing neuroblastoma tumor progression and metastasis. Thus, BG-PEG1600-TAT represents a potential clinical candidate for targeted therapy in neuroblastoma management.

Inhibitory Control Deficits Associated with Upregulation of CB1R in the HIV-1 Tat Transgenic Mouse Model of Hand

In the era of combined antiretroviral therapy, HIV-1 infected individuals are living longer lives; however, longevity is met with an increasing number of HIV-1 associated neurocognitive disorders (HAND) diagnoses. The transactivator of transcription (Tat) is known to mediate the neurotoxic effects in HAND by acting directly on neurons and also indirectly via its actions on glia. The Go/No-Go (GNG) task was used to examine HAND in the Tat transgenic mouse model. The GNG task involves subjects discriminating between two stimuli sets in order to determine whether or not to inhibit a previously trained response. Data reveal inhibitory control deficits in female Tat(+) mice (p = .048) and an upregulation of cannabinoid type 1 receptors (CB1R) in the infralimbic (IL) cortex in the same female Tat(+) group (p < .05). A significant negative correlation was noted between inhibitory control and IL CB1R expression (r = −.543, p = .045), with CB1R expression predicting 30% of the variance of inhibitory control (R2 = .295, p = .045). Furthermore, there was a significant increase in spontaneous excitatory postsynaptic current (sEPSC) frequencies in Tat(+) compared to Tat(−) mice (p = .008, across sexes). The increase in sEPSC frequency was significantly attenuated by bath application of PF3845, a fatty acid amide hydrolase (FAAH) enzyme inhibitor (p < .001). Overall, the GNG task is a viable measure to assess inhibitory control deficits in Tat transgenic mice and results suggest a potential therapeutic treatment for the observed deficits with drugs which modulate endocannabinoid enzyme activity.Graphical Results of the Go/No-Go operant conditioning task reveal inhibitory control deficits in female transgenic Tat(+) mice without significantly affecting males. The demonstrated inhibitory control deficits appear to be associated with an upregulation of cannabinoid type 1 receptors (CB1R) in the infralimbic (IL) cortex in the same female Tat(+) group.

Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats.

Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated the role of HIV-1 transactivator of transcription (Tat) protein in the alterations of nicotine-mediated behavior and the signaling pathway observed in the HIV-1 transgenic rats. Rats received bilateral microinjection of recombinant Tat1–86 (25 μg/side) or vehicle directed at ventral tegmental area (VTA) followed by locomotor testing in response to 13 daily intravenous injections of nicotine (0.05 mg/kg, freebase, once/day) or saline. Further, we examined the phosphorylated levels of CREB (pCREB) and ERK1/2 (pERK1/2) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and VTA. Tat diminished baseline activity in saline control rats, and attenuated nicotine-induced behavioral sensitization. Following repeated saline injection, the basal levels of pERK1 in the NAc and VTA and pERK2 in VTA were lower in the vehicle control group, relative to the Tat group. After repeated nicotine injection, pERK1 in NAc and VTA and pERK2 in VTA were increased in the vehicle group, but not in the Tat group. Moreover, repeated nicotine injections decreased pCREB in the PFC and VTA in the Tat group but not in the vehicle group. Thus, these findings indicate that the direct injection of Tat at the VTA may mediate CREB and ERK activity in response to nicotine-induced locomotor activity.

Convergent evolution of ribonuclease h in LTR retrotransposons and retroviruses.

Ty3/Gypsy long terminals repeat (LTR) retrotransposons are structurally and phylogenetically close to retroviruses. Two notable structural differences between these groups of genetic elements are 1) the presence in retroviruses of an additional envelope gene, env, which mediates infection, and 2) a specific dual ribonuclease H (RNH) domain encoded by the retroviral pol gene. However, similar to retroviruses, many Ty3/Gypsy LTR retrotransposons harbor additional env-like genes, promoting concepts of the infective mode of these retrotransposons. Here, we provide a further line of evidence of similarity between retroviruses and some Ty3/Gypsy LTR retrotransposons. We identify that, together with their additional genes, plant Ty3/Gypsy LTR retrotransposons of the Tat group have a second RNH, as do retroviruses. Most importantly, we show that the resulting dual RNHs of Tat LTR retrotransposons and retroviruses emerged independently, providing strong evidence for their convergent evolution. The convergent resemblance of Tat LTR retrotransposons and retroviruses may indicate similar selection pressures acting on these diverse groups of elements and reveal potential evolutionary constraints on their structure. We speculate that dual RNH is required to accelerate retrotransposon evolution through increased rates of strand transfer events and subsequent recombination events.

A Randomized Comparison Study Assessing the Impact of Cilostazol on the Heart Rate and Arrhythmias by 24-Hour Ambulatory Holter Electrocardiographic Monitoring after Drug-Eluting Stent Implantation for Coronary Artery Disease

Cilostazol may have a positive chronotropic or pro-arrhythmic effect. However, there have been no randomized trials to confirm these effects. This randomized prospective trial compared dual (DAT, aspirin and clopidogrel, n=114) versus triple antiplatelet therapy (TAT, DAT plus cilostazol, n=113) at baseline and after six months in patients receiving intracoronary drug-eluting stents (DES). The primary endpoint was the 24-hour heart rate (24h-HR) at six months determined using 24h-Holter ECG monitoring. The secondary endpoints were the 24h-HR ≥70 bpm, 24h-HR increase ≥5 bpm and the counts or presence of arrhythmias. At six months after DES implantation, the 24h-HR (73 [68-83] vs. 68 [62-75] bpm, p＜0.001), presence of a 24h-HR ≥70 bpm (71.4 vs. 47.1%, p＜0.001) and presence of a 24h-HR increase ≥5 bpm (44.8 vs. 24.5%, p=0.002) were significantly higher for the TAT group than for the DAT group. A multivariate analysis showed that the use of cilostazol (OR: 3.10, p=0.035) and a baseline 24h-HR ＜70 bpm (OR: 4.60, p＜0.001) were strong predictors of a 24h-HR increase ≥5 bpm. However, there were no significant intergroup differences in arrhythmias. Cilostazol appears to result in an increase in the 24h-HR after DES implantation. Therefore, some caution should be exercised regarding the use of cilostazol in patients with tachycardia, when planning DES implantation.

Cilostazol Eliminates Adverse Smoking Outcome in Patients With Drug-Eluting Stent Implantation

The present study investigated whether cilostazol can eliminate adverse smoking outcome after percutaneous coronary intervention (PCI). A total of 914 patients with successful drug-eluting stent (DES) implantation were randomly assigned to dual antiplatelet therapy (DAT; aspirin and clopidogrel, n=457) or to triple antiplatelet therapy (TAT; DAT with cilostazol, n=457). The effect of smoking on 2-year major adverse cardio/cerebrovascular events (MACCE) in both the TAT and DAT groups was evaluated. Total MACCE were not significantly different between the 2 anti-platelet regimens (9.8% in TAT vs. 11.4% in DAT groups, P=0.45), but the adverse effects of smoking on clinical outcome were different between DAT vs. TAT. Current smokers had a higher prevalence of MACCE than non-smokers in the DAT group (16.7% vs. 9.5%, P=0.04). In the TAT group, however, the adverse effect of smoking was abolished (9.2% vs. 10.1%, P=0.85). Regarding the effects of smoking on the antiplatelet effects of DAT or TAT, post-treatment platelet reactivity (in P2Y12 reaction units; PRU) in current smokers was not significantly lower than that in non-smokers in the DAT group, whereas, in the TAT group, it was significantly lower than that of non-smokers (189±88 vs. 216±89 PRU, P=0.01). Adverse clinical effects of smoking may be eliminated by the addition of cilostazol to DAT after DES implantation. This may be due to the stimulation of cilostazol's antiplatelet effects by smoking.

TCT-153 Comparison of effect that ticagrelor and triple antiplatelet therapy affect platelet reactivity

Background: High platelet reactivity (HPR) is associated with poor prognosis in coronary artery disease. Recently PLATO subgroup analysis showed that ticagrelor is better clinical outcome than the clopidogrel,whichwas relatedwith lowHPR.Alsomany studies reported that adjunctive cilostazol to dual antiplatelet therapy (DAPT) (so called triple antiplatelet therapy; TAT) is better clinical outcome than DAPT, which was associated with a greater antiplatelet effect at 30 days. Thus, this study was designed to compare the effect of ticagrelor and TAT on platelet reactivity with PRU and ARU values. Methods: This study was composed of total 65 patients underwent the coronary stenting. All patients received a 600-mg loading dose of clopidogrel or a 180-mg loading dose of ticagrelor and concomitant aspirin therapy. After patients underwent coronary stenting, theywere nonrandomly assigned to 1 of 4 groups:DAPT group (n1⁄415), clopidogrel of 75 mg daily; ticagrelor group (n1⁄420), ticagrelor of 180 mg daily; TAT group (n1⁄415), adjunctive cilostazol of 100mg twice daily to clopidogrel of 75mg daily; and triple switch group (n1⁄415), switch of ticagrelor to TAT since 3rd day. The platelet reactivity was assessed by ARU and PRU values at day 2 and day 7, respectively. Results: The average PRU value was lower in ticagrelor and TAT group than DAPT throughout the study period but the average ARU value did not differ among the 4 groups. The 2nd day average ARU was lower in the TAT group than ticagrelor group (405 vs. 510, p<0.01) and there was no significant difference on 7th day average ARU value. In ticagrelor group, 7th day average ARU is lower than 2th day ARU (458 vs. 510, p<0.05). Compared with TAT group, ticagrelor group had significantly lower PRU level at 2nd day and 7th day, respectively (91 vs. 162, p<0.05, 50 vs. 163, p<0.01). The 2nd day average PRU value of triple switch group was 70 which was similar to PRU of ticagrelor group and 7th day average PRU (151) was similar to that of TAT group. Conclusions: The ticagrelor and TAT therapy had the lower PRU level than DAPT and especially, ticagrelor showed the lowest incidence of HPR. This indicates that ticagrelor is more effective in HPR treatment than TAT.

Addition of Cilostazol to Conventional Dual Antiplatelet Therapy Reduces the Risk of Cardiac Events and Restenosis After Drug‐Eluting Stent Implantation: A Meta‐Analysis

This meta-analysis was performed to compare the risk of cardiac events and restenosis between triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) and conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) in drug-eluting stents (DES) implantation patients. We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation. Five clinical trials were involved in the study. TAT was associated with a 36% reduction in major adverse cardiac events (MACE; odds ratio (OR) = 0.64; 95% confidence interval (CI) = 0.51-0.81, P < .01), a 40% reduction (OR = 0.60, 95% CI = 0.44-0.80; P < .01) in target vessel revascularization (TVR), a 44% reduction (OR = 0.56, 95% CI = 0.34-0.91; P = .02) in target lesion revascularization (TLR) and a 47%/44% reduction in in-segment/in-stent restenosis (P < .01) and lower in-segment/in-stent late loss (P < .01). As regards to the safety assessment, there was no significant difference about the risk of stent thrombosis and bleeding between TAT and DAT group, while the risk of gastrointestinal trouble was significantly higher in TAT group (OR = 2.46, 95% CI = 1.25-4.86; P < .01). Addition of cilostazol to DAT reduced the incidence of MACE, TVR, and TLR after DES implantation. TAT also reduced the risk of restenosis and late loss in patients after DES implantation.

Randomized comparison of new dual-antiplatelet therapy (aspirin, prasugrel) and triple-antiplatelet therapy (aspirin, clopidogrel, cilostazol) using P2Y12 point-of-care assay in patients with STEMI undergoing primary PCI

BackgroundBoth new dual antiplatelet therapy (DAT; aspirin and prasugrel) and triple antiplatelet therapy (TAT; aspirin, clopidogrel and cilostazol) are more potent than classic DAT (aspirin and clopidogrel). We compared the antiplatelet efficacy between new DAT and TAT in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary coronary percutaneous coronary intervention (PCI). MethodsForty patients who were eligible for primary PCI were prospectively randomized to DAT group (n=20) or TAT group (n=20) immediately after hospital arrival. The primary end point was P2Y12 reaction unit (PRU) determined with the VerifyNow P2Y12 point-of-care assay at the time of discharge. ResultsPRU value at discharge was significantly lower in patients receiving DAT compared with that of TAT (84.5±44.7 vs. 128.4±74.9, p=0.032). Percent platelet inhibition was significantly higher for DAT compared with TAT at discharge (72.1±12.2 vs. 57.5±23.5, p=0.020). Inter-patient variability of PRU values at discharge was significantly smaller in patient taking DAT compared with TAT (p=0.026). ConclusionA new DAT is more potent antiplatelet therapy than TAT in patients with STEMI undergoing primary PCI.

ADDITION OF CILOSTAZOL TO CONVENTIONAL DUAL ANTIPLATELET THERAPY REDUCING THE RISK OF CARDIAC EVENTS AND RESTENOSIS AFTER DRUG-ELUTING STENT IMPLANTATION: A META-ANALYSIS

ObjectivesRelative efficacy and safety of triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) compared with conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) remained controversial. This meta-analysis...

Inhibitory Interaction Between Calcium Channel Blocker and Clopidogrel - Efficacy of Cilostazol to Overcome It -

The clinical effect of, and additive measures to overcome the possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in Asian patients undergoing percutaneous coronary intervention is unknown. A total of 900 Korean patients enrolled for the multicenter, prospective, randomized Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial were divided into 4 groups depending on CCB prescription and type of anti-platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in a 2 × 2 factorial manner. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On-treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay. Concomitant CCB use increased OPR in the DAT group (mean ± SEM: 251.2 ± 7.6 vs. 225.6 ± 5.1; P=0.008), but not in the TAT group (214.5±9.1 vs. 203.4 ± 5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346). Addition of cilostazol to DAT reduced OPR and clinical events in patients taking CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB without concomitant cilostazol use was a significant predictor of total thrombotic events. Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol.

Randomized Trial of Two Mind–Body Interventions for Weight-Loss Maintenance

Regain of weight after initial weight loss constitutes a major factor contributing to the escalating obesity epidemic. The objective of this study was to determine the feasibility and clinical impact of two mind-body interventions for weight-loss maintenance. Randomized, balanced, controlled trial. Large-group model health maintenance organization. Overweight and obese adults were recruited to a 12-week behavioral weight-loss program. Participants meeting threshold weight loss and attendance requirements were eligible for randomization. The three weight-loss maintenance interventions were qigong (QI), Tapas Acupressure Technique (TAT (registered trademark of Tapas Fleming, L.Ac.), and a self-directed support (SDS) group as an attention control. The main outcome measure was weight loss maintenance at 24 weeks postrandomization. Patient interviews explored additional benefits of the interventions, as well as barriers and facilitators to compliance. Eighty-eight percent (88%) of randomized patients completed the study. There were no significant study-related adverse events. At 24 weeks, the TAT group maintained 1.2 kg more weight loss than the SDS group did (p = 0.09), and 2.8 kg more weight loss than the QI group did (p = 0.00), only regaining 0.1 kg. A separation test (0.05 level, 0.95 power) indicated that TAT merits further study. A secondary analysis revealed that participants reporting a previous history of recurrent unsuccessful weight loss were more likely to regain weight if assigned to the SDS arm, but this effect was suppressed in both the QI and TAT groups (p = 0.03). Although QI participants reported important general health benefits, the instruction sequence was too brief, given the complexity of the intervention. TAT warrants further research for weight-loss maintenance. Any further research on qigong should use a modification of our protocol.

Outcome of simian-human immunodeficiency virus strain 89.6p challenge following vaccination of rhesus macaques with human immunodeficiency virus Tat protein.

The regulatory proteins Nef, Rev, and Tat of human immunodeficiency virus type 1 (HIV-1) are attractive targets for vaccine development, since induction of effective immune responses targeting these early proteins may best control virus replication. Here we investigated whether vaccination with biologically active Tat or inactive Tat toxoid derived from HIV-1(IIIB) and simian-human immunodeficiency virus (SHIV) strain 89.6p would induce protective immunity in rhesus macaques. Vaccination induced high titers of anti-Tat immunoglobulin G in all immunized animals by week 7, but titers were somewhat lower in the 89.6p Tat group. Dominant B-cell epitopes mapped to the amino terminus, the basic domain, and the carboxy-terminal region. Tat-specific T-helper responses were detected in 50% of immunized animals. T-cell epitopes appeared to map within amino acids (aa) 1 to 24 and aa 37 to 66. In addition, Tat-specific gamma interferon responses were detected in CD4+ and/or CD8+ T lymphocytes in 11 of 16 immunized animals on the day of challenge. However, all animals became infected upon intravenous challenge with 30 50% minimal infective doses of SHIV 89.6p, and there were no significant differences in viral loads or CD4+ T-cell counts between immunized and control animals. Thus, vaccination with HIV-1(IIIB) or SHIV 89.6p Tat or with Tat toxoid preparations failed to confer protection against SHIV 89.6p infection despite robust Tat-specific humoral and cellular immune responses in some animals. Given its apparent immunogenicity, Tat may be more effective as a component of a cocktail vaccine in combination with other regulatory and/or structural proteins of HIV-1.

Magellan Air expands in association with TAT Group

Magellan Air expands in association with TAT Group