Studies on Incretins and Cardiovascular Function

Background Type 2 diabetes (T2DM) is a strong risk factor for coronary heart disease (CHD). A great many diabetic subjects suffer from congestive heart failure (CHF), a condition with a high concomitant mortality. So far, attempts aimed at reducing macrovascular complications in T2DM have been essentially futile. Hence, there is a need for finding glucose-lowering agents that exert direct positive effects on vasculature and the heart. Glucagon-like peptide-1(GLP-1) is a peptide secreted from the L-cells in the small intestine. GLP-1 decreases plasma glucose by increasing insulin secretion without an increased risk for hypoglycemia. Aims The aim of this work was to evaluate the putative role and potential effects of GLP-1 and related peptides on the vasculature and heart and to elucidate the mechanisms behind these effects. Study I and II These papers are based on studies performed within the ULSAM (Uppsala longitudinal study of adult men) cohort, a community-based prospective cohort study of elderly men started in 1970. The participants were examined at age 50 and 70 and the data was completed with annual updates on mortality and morbidity. The examination at age 70 forms the baseline of the present studies. A subsample from this cohort consisting of 509 men performed an oral glucose tolerance test (OGTT), plasma samples were stored frozen and GLP-1 concentrations were analyzed in 2007. At baseline, echocardiographic measurements of left ventricular function were done. Information concerning incident disease was collected from official Swedish registries. The studies did not reveal any longitudinal associations between plasma GLP-1 levels and the incidence of CHD or CHF. Cross-sectionally, however, we found correlative associations between plasma GLP-1 levels and impaired glucose tolerance and diastolic cardiac dysfunction. Study III This was a double-blinded randomized cross-over study. Twenty patients with T2DM hospitalized for decompensated congestive heart failure (CHF) were enrolled in the study. Primary outcome was the proportion of subjects achieving a 20% increase of cardiac index (CI) and a 20% decrease of pulmonary capillary wedge pressure (PCWP), i.v. infusions with exenatide or placebo, 18 hours apart. Hemodynamic variables were monitored by heart catheterization. Exenatide evoked a 21% increase in CI, a 29% increase of heart rate, a 15% decrease of PCWP and a 17% decrease of right atrial pressure. Study IV The aim of this study was to investigate whether exenatide could protect against endothelial dysfunction induced by lipotoxicity and if there were any differences in vasorelaxant capacity between GLP-1 (7-36), the degradation metabolite GLP-1 (9-36) and exenatide in femoral arterial rings from non-diabetic rats ex vivo. Exenatide did not protect against lipotoxicity, whereas GLP-1 (7-36) and GLP-1 (9-36) exerted vasorelaxation with 23% and 38%, respectively, vs. only 3% with exenatide. Study V We studied the effects of exenatide, GLP-1 (7-36) and GLP-1 (9-36) on human coronary artery endothelial cell (HCAEC) proliferation and potential underlying mechanisms. Exenatide, GLP-1 (7-36) and GLP-1(9-36) elicited dose-dependent increases in DNA synthesis and increased cell numbers. This was associated with enhanced eNOS and Akt activity, which – along with the augmented cell proliferation - were inhibited by PKA-, PI3K-, Akt- and eNOS-inhibitors and by a GLP-1 receptor antagonist. Conclusions Altered plasma GLP-1 levels were not found to predict incident CHD or CHF, while significant cross-sectional correlations were found between GLP-1 impaired glucose tolerance (IGT) and diastolic cardiac function in elderly men. GLP-1 and related peptides stimulate proliferation of HCAEC cells, exert vasorelaxant effects on rat arterial rings ex vivo and evoke potent hemodynamic effects in T2DM patients with CHF. These effects seem to occur independent of changes in glucose concentrations. These findings prompt further efforts and mechanistic studies aimed at characterizing potential beneficial cardiovascular effects of incretin hormones in the clinical management of T2DM patients

Biosafety and Biohazards: Understanding Biosafety Levels and Meeting Safety Requirements of a Biobank.

When it comes to biobanking and working with different types of laboratory specimens, it is important to understand potential biohazards to ensure safety of the operator and laboratory personnel. Biological safety levels (BSL) are a series of designations used to inform laboratory personnel about the level of biohazardous risks in a laboratory setting. There are a total of four levels ranked in order of increasing risk as stipulated by the Center of Disease Control and Prevention (CDC) (Biosafety in microbiological and biomedical laboratories, 5th edn. HHS publication no. (CDC) 21-1112. https://www.cdc.gov/biosafety/publications/bmbl5/bmbl.pdf . Accessed 2 Jan 2016, 2009). We will address the main distinctions between these levels including briefly introducing hazards characteristics that classify biohazardous agents, as well as define the essentials in meeting safety requirements

Quantum Error Correction and One-Way LOCC State Distinguishability

We explore the intersection of studies in quantum error correction and quantum local operations and classical communication (LOCC). We consider one-way LOCC measurement protocols as quantum channels and investigate their error correction properties, emphasizing an operator theory approach to the subject, and we obtain new applications to one-way LOCC state distinguishability as well as new derivations of some established results. We also derive conditions on when states that arise through the stabilizer formalism for quantum error correction are distinguishable under one-way LOCC.Comment: 20 page

Preoperative Chemotherapy and Irradiation in the Treatment of Soft Tissue Sarcomas of the Lower Extremities: Preliminary Report of Experience at Henry Ford Hospital

The development of effective chemotherapy and improved techniques of radiation therapy offer the possibility of managing soft tissue sarcomas so that surgery may need to be less radical than in the past and amputation can be avoided. The low rates of local-regional and systemic recurrence that have resulted from using innovative combinations of chemotherapy, radiation therapy, and conservative surgery encouraged us to use preoperative intraarterial adriamycin (doxorubicin) with or without radiation therapy for three cases of soft tissue sarcomas of the lower extremities. The rationale for this therapy is also discussed

Continuity of the roots of a polynomial

Let $K$ be an algebraically closed field with an absolute value. This note gives an elementary proof of the classical result that the roots of a polynomial with coefficients in $K$ are continuous functions of the coefficients of the polynomial.Comment: 9 pages; minor improvement

Vector Representations of Graphs and Distinguishing Quantum Product States with One-way LOCC

Distinguishing sets of quantum states shared by two parties using only local operations and classical communication measurements is a fundamental topic in quantum communication and quantum information theory. We introduce a graph-theoretic approach, based on the theory of vector representations of graphs, to the core problem of distinguishing product states with one-way LOCC. We establish a number of results that show how distinguishing such states can be framed in terms of properties of the underlying graphs associated with a set of vector product states. We also present a number of illustrative examples.Comment: some minor typos corrected, and Corollary 2 statement and proof correcte

Early Onset Angiosarcoma of the Breast Following Breast Conserving Therapy

Introduction: Breast angiosarcoma following treatment for breast cancer is a rare event and generally presents no earlier than 6 years after treatment. We identified 2 cases of early-onset angiosarcoma and evaluated patient and treatment factors. Methods: At our large multi-hospital health system, the tumor registry was searched for breast sarcoma from 2000-2020. Patient, tumor, and treatment details were collected. Results: 39 patients were identified, 4 with radiation induced angiosarcoma following breast cancer treatment (range 3-11 years). Two of the cases were early-onset, diagnosed at 3 and 4 years respectively. Patient 1 underwent BCT at age 44 for T1bN0 estrogen positive Her2 negative breast cancer. She presented 3 years later with progressive skin discoloration. After a delay of 3 months as multiple providers thought this was bruising secondary to trauma sustained during a fall, she was referred to breast surgery and punch biopsy was diagnostic for angiosarcoma (Figure 1). She underwent right mastectomy revealing 9.7-cm of high grade angiosarcoma. Patient 2 underwent BCT at 72 for T1cN1a estrogen positive Her2 negative breast cancer. She presented 4 years later with a suspicious skin finding. Punch biopsy was diagnostic for angiosarcoma. She underwent right mastectomy revealing 8-cm of high grade angiosarcoma. Conclusions: Radiation induced breast angiosarcoma is a known but rare entity typically occurring at least 6 years after treatment for breast cancer; however, it should remain high on the differential for patients with suspicious breast lesions before 6 years to avoid a delay in diagnosis as early-onset angiosarcoma does occur.https://scholarlycommons.henryford.com/merf2020caserpt/1126/thumbnail.jp

One-Way LOCC Indistinguishable Lattice States via Operator Structures

Lattice states are a class of quantum states that naturally generalize the fundamental set of Bell states. We apply recent results from quantum error correction and from one-way local operations and classical communication (LOCC) theory, that are built on the structure theory of operator systems and operator algebras, to develop a technique for the construction of relatively small sets of lattice states not distinguishable by one-way LOCC schemes. We also present examples, show the construction extends to generalized Pauli states, and compare the construction to other recent work

Prehospital exenatide in hyperglycemic stroke-A randomized trial

Objectives Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP-1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety. Materials & Methods Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test >= 1 and glucose >= 8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded. Results Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 +/- 1.9 vs 7.6 +/- 1.6; P = .56). No major adverse events were reported. Conclusions We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion.Peer reviewe