Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum.

Fetal alcohol spectrum disorders (FASD) caused by developmental ethanol exposure lead to cerebellar impairments, including motor problems, decreased cerebellar weight, and cell death. Alterations in the sole output of the cerebellar cortex, Purkinje cells, and central nervous system immune cells, microglia, have been reported in animal models of FASD. To determine how developmental ethanol exposure affects adult cerebellar microglia and Purkinje cells, we used a human third-trimester binge exposure model in which mice received ethanol or saline from postnatal (P) days 4-9. In adolescence, cerebellar cranial windows were implanted and mice were aged to young adulthood for examination of microglia and Purkinje cells in vivo with two-photon imaging or in fixed tissue. Ethanol had no effect on microglia density, morphology, dynamics, or injury response. However, Purkinje cell linear frequency was reduced by ethanol. Microglia-Purkinje cell interactions in the Purkinje Cell Layer were altered in females compared to males. Overall, developmental ethanol exposure had few effects on cerebellar microglia in young adulthood and Purkinje cells appeared to be more susceptible to its effects.

Age- and gender-stratified adult myometric reference values of isometric intrinsic hand strength.

STUDY DESIGN: Descriptive normative. INTRODUCTION: Intrinsic hand strength can be impacted by hand arthritis, peripheral nerve injuries, and spinal cord injuries. Grip dynamometry does not isolate intrinsic strength, and manual muscle testing is not sensitive to change in grades 4 and 5. The Rotterdam Intrinsic Hand Myometer is a reliable and valid test of intrinsic hand strength; however, no adult normative data are available. PURPOSE OF THE STUDY: To describe age- and gender-stratified intrinsic hand strength norms in subjects aged 21 years and above and to determine if factors known to predict grip dynamometry also predict measures of intrinsic hand strength. METHODS: Three trials of 5 measures of maximal isometric intrinsic strength were performed bilaterally by 607 "healthy-handed" adult males and females. Average strength values were stratified by age and gender. Data were analyzed to determine the influence of demographic and anthropometric variables on intrinsic strength. RESULTS: Intrinsic strength generally followed age and gender trends similar to grip dynamometry. Age, gender, body mass index, and the interaction between gender and body mass index were predictors of intrinsic strength, whereas in most cases, the hand being tested did not predict the intrinsic strength. DISCUSSION: With the addition of these findings, age- and gender-stratified hand intrinsic strength norms now span from age 4 through late adulthood. Many factors known to predict grip dynamometry also predict intrinsic myometry. Additional research is needed to evaluate the impact of vocational and avocational demands on intrinsic strength. CONCLUSIONS: These norms can be referenced to evaluate and plan hand therapy and surgical interventions for intrinsic weakness.

Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB.

BACKGROUND: We have previously shown that the thromboxane (TXA2) receptor agonist, U46619, can directly induce ventricular arrhythmias that were associated with increases in intracellular calcium in cardiomyocytes. Since TXA2 is an inflammatory mediator and induces direct calcium changes in cardiomyocytes, we hypothesized that TXA2 released during ischemia or inflammation could also cause cardiac remodeling. METHODS: U46619 (0.1-10 µM) was applied to isolated adult mouse ventricular primary cardiomyocytes, mouse ventricular cardiac muscle strips, and cultured HL-1 cardiomyocytes and markers of hypertrophy and cell death were measured. RESULTS: We found that TXA2 receptors were expressed in ventricular cardiomyocytes and were functional via calcium imaging. U46619 treatment for 24 h did not increase expression of pathological hypertrophy genes (atrial natriuretic peptide, ß-myosin heavy chain, skeletal muscle α-actin) and it did not increase protein synthesis. There was also no increase in cardiomyocyte size after 48 h treatment with U46619 as measured by flow cytometry. However, U46619 (0.1-10 µM) caused a concentration-dependent increase in cardiomyocyte death (trypan blue, MTT assays, visual cell counts and TUNEL stain) after 24 h. Treatment of cells with the TXA2 receptor antagonist SQ29548 and inhibitors of the IP3 pathway, gentamicin and 2-APB, eliminated the increase in cell death induced by U46619. CONCLUSIONS: Our data suggests that TXA2 does not induce cardiac hypertrophy, but does induce cell death that is mediated in part by IP3 signaling pathways. These findings may provide important therapeutic targets for inflammatory-induced cardiac apoptosis that can lead to heart failure.