A study of prevalence of peripheral arterial disease in type 2 diabetes mellitus using ankle-brachial index and its correlation with coronary artery disease and its risk factors

Background: Peripheral arterial disease (PAD) is one of the macrovascular complications of type 2 diabetes mellitus (T2DM). There is significant difference in the reported prevalence of PAD and its associated risk factors between Indian and Western studies. The purpose of this study was to examine the PAD complicating T2DM, in particular the influence of PAD on the risk of CAD.Methods: Randomly selected 100 T2DM patients presented to Guru Nanak Dev hospital were included. In addition to a detailed history and physical examination, anthropometric parameters like body mass index was measured. CAD in patients was diagnosed by a history of angina, ECG changes, any past history of CAD or any treatment taken for CAD. Ankle brachial index (ABI) was measured. Data was collected systematically and analyzed according to the standard statistical methods.Results: The prevalence of PAD was 15%. CAD was present in 31%. PAD was found to be significantly correlated with age, duration of diabetes, smoking, systolic blood pressure, diastolic blood pressure, prevalence of BMI >25 kg/m2, HbA1c and serum HDL ≤40 mg%. Old age, high HbA1c level, and dyslipidaemia were found to be significant independent predictors of CAD.Conclusions: Using ABI authors found evidence of PAD in 15% patients of T2DM. The prevalence of CAD was higher in patients with PAD. So, there is definite and strong correlation between PAD and CAD. Thus, the early diagnosis of PAD should alert the clinician to a high probability of underlying CAD

The Effects of Age and Alcohol on Lipid Metabolism in the Liver

Background: Alcohol-associated liver disease (ALD) encompasses the liver manifestation of chronic alcohol abuse, characterized by different stages of liver damage that progresses from fat accumulation to steatohepatitis, fibrosis and eventually cirrhosis. The severity of liver damage is influenced by age, which is also a predictor for ALD-related mortality. Thus, the purpose of this study was to investigate how aging and alcohol affect lipid metabolism in the liver. Methods: Rats aged 4 months, 8 months, 12 months, and 22 months-old were pair-fed Lieber-DeCarli control or ethanol diet for 6 weeks. Serum and liver were collected for analyses when rats were euthanized. Analyses included histopathology, measurements of non-esterified fatty acid content and hepatic triglyceride content, and gene expression.https://digitalcommons.unmc.edu/surp2022/1034/thumbnail.jp

Novel insights in pathophysiology of postoperative atrial fibrillation

OBJECTIVES: Atrial extrasystoles are usually benign; however, they can also trigger atrial fibrillation. It is most likely that if atrial extrasystoles provoke a larger amount of conduction disorders and a greater degree of endo-epicardial asynchrony, the risk of postoperative atrial fibrillation increases. To test this hypothesis, we investigated the effect of programmed atrial extrasystoles on endo-epicardial conduction and postoperative atrial fibrillation. METHODS: Twelve patients (58% male, age 68 ± 7 years) underwent simultaneous endo-epicardial mapping (256 electrodes) of the right atrium during sinus rhythm and programmed atrial extrasystoles provoked from the right atrial free wall. Areas of conduction block were defined as conduction delays of ≥12 milliseconds and endo-epicardial asynchrony as activation time differences of exact opposite electrodes of ≥15 milliseconds. RESULTS: Endo-epicardial mapping data of all programmed atrial extrasystoles were analyzed and compared with sinus rhythm (median preceding cycle length = 531 milliseconds [345-787] and median sinus rhythm cycle length = 843 milliseconds [701-992]). All programmed atrial extrasystoles were aberrant (severe, moderate, and mildly aberrant, respectively, n = 6, 3, and 3) and had a mean prematurity index of 50.1 ± 11.9%. The amount of endo-epicardial asynchrony (1% [1-2] vs 6.7 [2.7-16.9], P = .006) and conduction block (1.4% [0.6-2.6] vs 8.5% [4.2-10.4], P = .005) both increased during programmed atrial extrasystoles. Interestingly, conduction block during programmed atrial extrasystoles was more severe in patients (n = 4, 33.3%) who developed postoperative atrial fibrillation (5.1% [2.9-8.8] vs 11.3% [10.1-12.1], P = .004). CONCLUSIONS: Atrial conduction disorders and endo-epicardial asynchrony, which play an important role in arrhythmogenesis, are enhanced during programmed atrial extrasystoles compared with sinus rhythm. The findings of this pilot study provide a possible explanation for enhanced vulnerability for postoperative atrial extrasystoles to induce postoperative atrial fibrillation in patients after cardiac surgery

Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase

BACKGROUND: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. RESULTS: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. CONCLUSIONS: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function

Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression.

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair

Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies Using a Reduced-Intensity Conditioning Regimen and Third-Party Mesenchymal Stromal Cells

AbstractAllogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m2), melphalan (140 mg/m2), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward