Protection by beta-Hydroxybutyric acid against insulin glycation,lipid peroxidation and microglial cell apoptosis

Background

Diabetes mellitus is characterized jointly by hyperglycemia and hyperinsulinemia that make insulin more prone to be glycated and evolve insulin advanced glycation end products (Insulin- AGE). Here, we report the effect of beta-hydroxy butyrate (BHB) (the predominant ketone body) on the formation of insulin-AGE, insulin glycation derived liposomal lipid peroxidation and insulin-AGE toxicity in microglial cells.

Methods

The inhibitory effect of BHB was monitored as a result of insulin incubation in the presence of glucose or fructose using AGE-dependent fluorescence, Tyr fluorescence as well as anilinonaphthalenesulfonate (ANS) andthioflavin T (ThT) binding, and circular dichroism (CD) investigations. To study lipid peroxidation induced by insulin glycation, thiobarbituric acid (TBA) assay and thiobarbituric acid reactive substance (TBARS) monitoring were used. The effect of insulin–AGE on microglial viability was investigated by 3-(4, 5 dimethylthiazol-2-yl)—2, 5-diphenyltetrazoliumbromide (MTT) cell assay and Annexin V/propidium iodide (PI) staining.

Results

Here we are reporting the inhibitory effect of BHB on insulin glycation and generation of insulin-AGE as a possible explanation for insulin resistance. Moreover, the protective effect of BHB on consequential glycation derived liposomal lipid peroxidation as a causative event in microglial apoptosis is reported.

Conclusion

The reduced insulin fibril formation, structural inertia to glycation involved conformational changes, anti-lipid peroxidation effect, and increasing microglia viability indicated the protective effect of BHB that disclose insight on the possible preventive effect of BHB on Alzheimer’s disease.     

Influence of vessel diameter on the efficacy of distal protection devices during saphenous vein graft intervention

We sought to determine the influence of vessel diameter on the efficacy of distal protection devices during saphenous vein graft intervention. From the Filterwire EX Randomized Evaluation trial, in which patients who underwent saphenous vein graft stenting were randomized to distal protection with the GuardWire or FilterWire EX, outcomes in 572 patients were examined in vessel size tertiles. The 30-day composite incidence of major adverse cardiac events (MACEs) increased with vessel size and was 6.9%, 9.7%, and 14.9% in the smallest, middle, and largest tertiles, respectively (p = 0.04). MACE rates were relatively vessel size independent for the GuardWire but increased steadily with vessel size with the FilterWire EX. In the smallest tertile, MACEs were reduced by 71% with the FilterWire EX compared with the GuardWire (p = 0.05), with the devices showing similar event rates in the other tertiles.     

Feasibility and implications of an early discharge strategy after percutaneous intervention with abciximab in acute myocardial infarction (the CADILLAC Trial)

Early complications may hamper efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.     

Effect of plaque debulking and stenting on short- and long-term outcomes after revascularization of chronic total occlusions

OBJECTIVES: We evaluated the effect of plaque burden modification (debulking) on the short- and long-term clinical outcomes of patients with a totally occluded native coronary artery undergoing successful stent deployment. BACKGROUND: Although the primary success rate of crossing a chronic totally occluded coronary artery has improved with the development of new interventional devices and guidewires, the rate of acute reocclusion and restenosis remains high. METHODS: The in-hospital and late clinical outcomes of 150 patients who had undergone successful stenting of 176 chronic total occlusions were analyzed. After successful crossing of the lesion, 44 patients with 50 lesions underwent debulking by laser angioplasty, rotational or directional atherectomy followed by stenting, whereas 106 patients with 126 lesions underwent stent implantation without prior debulking. RESULTS: Baseline clinical and angiographic characteristics were similar for the two groups, except for a higher incidence of left anterior descending coronary artery location and longer lesions in the group of patients who underwent debulking prior to stenting. In-hospital mortality, myocardial infarction and repeat angioplasty rates were similar for the two groups. At a mean 14 +/- 8 months follow-up time, there were no deaths in either group, and target lesion revascularization rates were the same (16.3% in the debulking plus stent group vs. 14.4% in the stent alone group, p = NS). CONCLUSIONS: Treatment of chronic total native coronary artery occlusions with stent deployment with and without lesion modification (debulking) results in a favorable in-hospital outcome, with relatively low long-term target lesion revascularization rates.     

Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial

Background

Age is a strong independent predictor of outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Whether lower rates of reperfusion success contribute to the poor prognosis in elderly patients is unknown.

Methods

A formal ST-segment analysis substudy was performed in 695 patients undergoing primary PCI for AMI in the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Reperfusion success (determined by the magnitude of ST-segment elevation resolution [STR] after PCI) was evaluated in 4 age groups: <50 years (n = 163), ≥50 to <60 years (n = 187), ≥60 to <70 years (n = 194), and ≥70 years (n = 151).

Results

There were no differences in the age groups for angiographic procedural success >91% in all, P = .6), postprocedural Thrombolysis in Myocardial Infarction grade 3 flow >94%, P = .8), and the proportions of patients with complete, partial, or absent STR (P >.8). However, rates of 30-day mortality (0.6%, 1.1%, 3.6%, 6.0%, respectively) and major adverse cardiac events (MACE; 2.5%, 4.8%, 6.2% 9.3%, respectively) increased with age. Rates of mortality and MACE were also inversely related to the magnitude of STR. Absent STR (hazard ratio, 3.00; 95% CI, 1.37-6.58; P = .006) and age (hazard ratio, 1.34; 95% CI, 1.01-1.77; P = .04) were independent predictors of 30-day MACE by using multivariable modeling.

Conclusions

Lack of effective myocardial reperfusion is not a contributory mechanism responsible for the high morbidity and mortality rates observed in elderly patients. Nevertheless, advanced age and absent STR are both independent predictors of adverse outcomes after primary PCI, emphasizing the importance of successful reperfusion in the elderly population.     

Reliability of computer-assisted periacetabular osteotomy using a minimally invasive approach

Background

Periacetabular osteotomy (PAO) is the treatment of choice for younger patients with developmental hip dysplasia. The procedure aims to normalize the joint configuration, reduce the peak-pressure, and delay the development of osteoarthritis. The procedure is technically demanding and no previous study has validated the use of computer navigation with a minimally invasive transsartorial approach.

Methods

Computer-assisted PAO was performed on ten patients. Patients underwent pre- and postoperative computed tomography (CT) scanning with a standardized protocol. Preoperative preparation consisted of outlining the lunate surface and segmenting the pelvis and femur from CT data. The Biomechanical Guidance System was used intra-operatively to automatically calculate diagnostic angles and peak-pressure measurements. Manual diagnostic angle measurements were performed based on pre- and postoperative CT. Differences in angle measurements were investigated with summary statistics, intraclass correlation coefficient, and Bland–Altman plots. The percentage postoperative change in peak-pressure was calculated.

Results

Intra-operative reported angle measurements show a good agreement with manual angle measurements with intraclass correlation coefficient between 0.94 and 0.98. Computer navigation reported angle measurements were significantly higher for the posterior sector angle (\(1.65^{\circ }\), \(p=0.001\)) and the acetabular anteversion angle (\(1.24^{\circ }\), \(p=0.004\)). No significant difference was found for the center-edge (\(p=0.056\)), acetabular index (\(p=0.212\)), and anterior sector angle (\(p=0.452\)). Peak-pressure after PAO decreased by a mean of 13% and was significantly different (\(p=0.008\)).

Conclusions

We found that computer navigation can reliably be used with a minimally invasive transsartorial approach PAO. Angle measurements generally agree with manual measurements and peak-pressure was shown to decrease postoperatively. With further development, the system will become a valuable tool in the operating room for both experienced and less experienced surgeons performing PAO. Further studies with a larger cohort and follow-up will allow us to investigate the association with peak-pressure and postoperative outcome and pave the way to clinical introduction.

     

Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs

Background

Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study.

Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles

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