Euglycemic Diabetic Ketoacidosis in Type 1 Diabetes on Insulin Pump, with Acute Appendicitis: A Case Report.

Introduction: Recently, euglycemic diabetic ketoacidosis has been an increasing topic of discussion within emergency medicine literature. Euglycemic diabetic ketoacidosis can easily be missed, as a normal point-of-care glucose often mistakenly precludes the work-up of diabetic ketoacidosis.

Case Report: A 16-year-old female with a past medical history of type 1 diabetes presented to the emergency department with altered mental status, vomiting, and abdominal pain.

An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model.

Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable.

Multifunctional nanoagent for thrombus-targeted fibrinolytic therapy.

Background: Current thrombolytic therapies utilize exogenous plasminogen activators (PAs) to effectively lyse clots, restoring blood flow, and preventing tissue and organ death. These PAs may also impair normal hemostasis, leading to life-threatening bleeding, including intracerebral hemorrhage.

Aims: This study aims to develop new thrombus-targeted fibrinolytic agents that harness the multifunctional theranostic capabilities of nanomaterials, potentially allowing for the generation of efficacious thrombolytics while minimizing deleterious side effects.

FTY720 blocks egress of T cells in part by abrogation of their adhesion on the lymph node sinus.

Egress of lymphocytes from lymphoid tissues is a complex process in which Gαi-mediated signals play a decisive role. We show here that although FTY720, an agonist of the sphingosine 1-phosphate (S1P)(1) receptor, induces S1P(1) receptor internalization sufficiently in the presence or absence of Gαi2 or Gαi3, the drug blocks egress of wild-type (WT) and Gαi3-deficent T cells, but not Gαi2-deficient T cells, in both WT and Gαi2-deficient hosts. Intravital imaging of lymph nodes revealed that all three groups of T cells approached and engaged cortical sinusoids similarly in the presence or absence of FTY720.

Reciprocal function of Galphai2 and Galphai3 in graft-versus-host disease.

This study delineates specific functions of Galphai2 and Galphai3 in T cell mobilization during the development of graft-versus-host disease (GVHD) and reveals reciprocal effects of these two G proteins on the onset and morbidity of the disease. A deletion of Galphai2 hampered trafficking of pathogenic T cells from secondary lymphoid tissues to inflammatory sites and sufficiently prevented GVHD. In contrast, a severer disease was induced in mice adoptively transferred with Galphai3-deficient T cells than those mice transferred with wild-type T cells.

Inhibition of G alpha i2 activation by G alpha i3 in CXCR3-mediated signaling.

G protein-coupled receptors (GPCRs) convey extracellular stimulation into dynamic intracellular action, leading to the regulation of cell migration and differentiation. T lymphocytes express G alpha(i2) and G alpha(i3), two members of the G alpha(i/o) protein family, but whether these two G alpha(i) proteins have distinguishable roles guiding T cell migration remains largely unknown because of a lack of member-specific inhibitors. This study details distinct G alpha(i2) and G alpha(i3) effects on chemokine receptor CXCR3-mediated signaling.

2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.

We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog.

Role of phospholipase D signaling in ethanol-induced inhibition of carbachol-stimulated DNA synthesis of 1321N1 astrocytoma cells.

Inhibition of astrocyte proliferation has been suggested to be an important event in the developmental neurotoxicity associated with ethanol. We have previously shown that the acetylcholine analog carbachol induces astroglial cell proliferation through activation of muscarinic M3 receptors, and that ethanol strongly inhibits this effect by inhibiting activation of protein kinase C (PKC) zeta and its down-stream effector 70-kDa ribosomal S6 kinase (p70S6K). In this study, we investigated whether inhibition by ethanol of this signal transduction pathway in 1321N1 human astrocytoma cells may be due, at least in part, to inhibition of the formation of the PKC zeta activator phosphatidic acid (PA), which is formed by hydrolysis of phosphatidylcholine by phospholipase D (PLD).