Deficits in ERK and CREB activation in the hippocampus after traumatic brain injury.

Traumatic brain injury (TBI) activates several protein kinase signaling pathways in the hippocampus that are critical for hippocampal-dependent memory formation. In particular, extracellular signal-regulated kinase (ERK), a protein kinase activated during and necessary for hippocampal-dependent learning, is transiently activated after TBI. However, TBI patients experience hippocampal-dependent cognitive deficits that occur for several months to years after the initial injury.

Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats.

Background: Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment.

Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase.

Purpose: Dysregulation of the insulin-like growth factor-I receptor (IGF-IR) signaling pathway has been implicated in the development of many types of tumors, including prostate, colon, breast, pancreatic, ovarian, and sarcomas. Agents that inhibit IGF-IR activity may be useful in treatment of patients with various cancers.

Experimental Design: Kinase assays were used to identify a selective small-molecule inhibitor of IGF-IR activity.

Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia.

For the past 20 years, various laboratories throughout the world have shown that mild to moderate levels of hypothermia lead to neuroprotection and improved functional outcome in various models of brain and spinal cord injury (SCI). Although the potential neuroprotective effects of profound hypothermia during and following central nervous system (CNS) injury have long been recognized, more recent studies have described clinically feasible strategies for protecting the brain and spinal cord using hypothermia following a variety of CNS insults. In some cases, only a one or two degree decrease in brain or core temperature can be effective in protecting the CNS from injury.

Vocal fold surface hydration: a review.

Vocal fold surface liquid homeostasis contributes to optimal vocal physiology. In this paper we review emerging evidence that vocal fold surface liquid is maintained in part by salt and water fluxes across the epithelium. Based on recent immunolocalization and electrophysiological findings, we describe a transcellular pathway as one mechanism for regulating superficial vocal fold hydration.

Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R).

The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.

Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.

The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.

Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.

The evaluation of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines as inhibitors of the IGF-1R (IGF-IR) receptor tyrosine kinase is reported. Examples demonstrate nanomolar potencies in in vitro enzyme and mechanistic cellular assays as well as promising in vivo pharmacokinetics in rat.

Effects of isomerization on the measured thermochemical properties of deprotonated glycine/protic-solvent clusters.

The thermochemical properties associated with the formation of an isomeric distribution of ROHNH(2)CH(2)COO(-) clusters (R=H, CH(3), C(2)H(5)) are measured by using high-pressure mass spectrometry. A comparison of the measured properties with calculated values provides new insights into the thermochemical effects arising from the isomeric nature of this clustering system. When the distribution of isomers is correctly accounted for, the measured values of DeltaH degrees , DeltaS degrees , and DeltaG degrees (298) consistently agree, to a very high degree of accuracy, with those predicted by MP2(full)/6-311++G(d,p)//B3LYP/6-311++G(d,p) calculations.

Uric acid deposits in symbiotic marine algae.

The symbiosis between cnidarians and dinoflagellate algae is not understood at the cell or molecular level, yet this relationship is responsible for the formation of thousands of square kilometres of coral reefs. We have investigated the nature of crystalline material prominent within marine algal symbionts of Aiptasia sp. anemones.

Use of a nitinol gooseneck snare catheter for removal of adult Dirofilaria immitis in two cats.

Case Description: 2 cats were examined because of congestive heart failure secondary to heartworm infection.

Clinical Findings: One cat had severe abdominal distention and the other had dyspnea secondary to chylothorax. Both had loud right-sided heart murmurs, precordial thrills, and jugular distension.

Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats.

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats.

Acute death in heartworm-infected cats: unraveling the puzzle.

Although the acute death syndrome in feline heartworm disease is widely recognized, its pathogenesis remains a mystery. The most widely held hypothesis is that an acute anaphylactic reaction, perhaps precipitated by the death of the parasite, is the underlying cause. This study investigated the role of the physical form of antigen (Ag) in the ensuing reaction when Dirofilaria immitis-sensitized cats are challenged by intravenous (IV) administration of heartworm Ag.

Infrared multiple photon dissociation spectra of proton- and sodium ion-bound glycine dimers in the N-H and O-H stretching region.

The proton- and the sodium ion-bound glycine homodimers are studied by a combination of infrared multiple photon dissociation (IRMPD) spectroscopy in the N-H and O-H stretching region and electronic structure calculations. For the proton-bound glycine dimer, in the region above 3100 cm (-1), the present spectrum agrees well with one recorded previously. The present work also reveals a weak, broad absorption spanning the region from 2650 to 3300 cm (-1).

Modulation of the cAMP signaling pathway after traumatic brain injury.

Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream target, protein kinase A, from 15 min to 48 h after moderate FPI.

Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency.

Objective: To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF).

Design: Placebo-controlled, double-blind, multicenter, randomized trial.

Animals: 124 dogs with compensated mitral valve regurgitation (MR).

Immunological change in a parasite-impoverished environment: divergent signals from four island taxa.

Dramatic declines of native Hawaiian avifauna due to the human-mediated emergence of avian malaria and pox prompted an examination of whether island taxa share a common altered immunological signature, potentially driven by reduced genetic diversity and reduced exposure to parasites. We tested this hypothesis by characterizing parasite prevalence, genetic diversity and three measures of immune response in two recently-introduced species (Neochmia temporalis and Zosterops lateralis) and two island endemics (Acrocephalus aequinoctialis and A. rimitarae) and then comparing the results to those observed in closely-related mainland counterparts.

The effect of amlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone system in the dog.

Excessive aldosterone secretion is detrimental to the heart, vessels and kidneys, contributing to hypertension and the signs and progression of heart failure. Aldosterone secretion, abnormally elevated in heart failure and hypertension, can be blunted with angiotensin-converting enzyme inhibitors. Amlodipine, used to treat hypertension and heart failure, was hypothesized to activate the renin-angiotensin-aldosterone system (RAAS).

Efficacy of omega-3 fatty acids in children and adults with IgA nephropathy is dosage- and size-dependent.

Previous studies that have evaluated fish oil preparations in patients with IgA nephropathy (IgAN) have produced a wide range of conclusions. Proposed explanations for these discordant results have not provided a unifying hypothesis. Results from two clinical trials were analyzed to examine whether there is a dosage-dependent effect of Omacor, a purified preparation of omega-3 fatty acids, in patients with IgAN.

Estimation of 24-h aldosterone secretion in the dog using the urine aldosterone:creatinine ratio.

Objectives: One potential method of evaluating renin-angiotensin-aldosterone system (RAAS) activation involves the quantification of urinary aldosterone excretion. While blood concentrations of aldosterone are easily obtained, results may be misleading because of minute-to-minute variation in aldosterone secretion and subsequent blood concentrations. Urinary aldosterone concentration measurement represents a more consistent "pooled" index of aldosterone secretion, but obtaining 24-h urine samples is time-consuming, difficult, and fraught with potential error.

Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury.

Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI.