Model of mouse pancreaticoduodenal transplantation

Our technical procedure for mouse pancreaticoduodenal transplantation is described. A number of methods were attempted. Among them, a modification of S. Lee's method was thought to be the most successful procedure, which was performed with end-to-side anastomosis of the donor portal vein to the inferior vena cava and that of the donor aortic patch to the aorta. Even with this method, however, arterial thrombosis or venous stenosis of the anastomoses was inevitable without the use of some devices as well as special skills in microsurgery.     

Collaborative Hypertension Case Management by Registered Nurses and Clinical Pharmacy Specialists within the Patient Aligned Care Teams (PACT) Model

BACKGROUND

Clinical Pharmacy Specialists (CPSs) and Registered Nurses (RNs) are integrally involved in the Patient Aligned Care Teams (PACT) model, especially as physician extenders in the management of chronic disease states. CPSs may be an alternative to physicians as a supporting prescriber for RN case management (RNCM) of poorly controlled hypertension.

OBJECTIVE

To compare CPS-directed versus physician-directed RNCM for patients with poorly controlled hypertension.

DESIGN

Non-randomized, retrospective comparison of a natural experiment.

SETTING

A large Midwestern Veterans Affairs (VA) medical center.

INTERVENTION

Utilizing CPSs as alternatives to physicians for directing RNCM of poorly controlled hypertension.

PATIENTS

All 126 patients attended RNCM appointments for poorly controlled hypertension between 20 September 2011 and 31 October 2011 with either CPS or physician involvement in the clinical decision making. Patients were excluded if both a CPS and a physician were involved in the index visit, or they were enrolled in Home Based Primary Care, or if they displayed non-adherence to the plan.

MAIN MEASURES

All data were obtained from review of electronic medical records. Outcomes included whether a patient received medication intensification at the index visit, and as the main measure, blood pressures between the index and next consecutive visit.

KEY RESULTS

All patients had medication intensification. Patients receiving CPS-directed RNCM had greater decreases in systolic blood pressure compared to those receiving physician-directed RNCM (14?±?13 mmHg versus 10?±?11 mmHg; p?=?0.04). After adjusting for the time between visits, initial systolic blood pressure, and prior stroke, provider type was no longer significant (p?=?0.24). Change in diastolic blood pressure and attainment of blood pressure < 140/90 mm Hg were similar between groups (p?=?0.93, p?=?0.91, respectively).

Conclusions

CPS-directed and physician-directed RNCM for hypertension demonstrated similar blood pressure reduction. These results support the utilization of CPSs as prescribers to support RNCM for chronic diseases.

     

Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations

Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ_//), perpendicular (λ_⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ_⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ_// and λ_⊥. In contrast, more mildly affected patients had much smaller changes in λ_// and λ_⊥. These data suggest that myelin, the structure responsible in part for the λ_⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ_//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.     

Effect of (+)-methamphetamine on path integration learning,novel object recognition,and neurotoxicity in rats

RATIONALE: Methamphetamine (MA) has been implicated in cognitive deficits in humans after chronic use. Animal models of neurotoxic MA exposure reveal persistent damage to monoaminergic systems but few associated cognitive effects. OBJECTIVES: Since questions have been raised about the typical neurotoxic dosing regimen used in animals and whether it adequately models human cumulative drug exposure, these experiments examined two different dosing regimens. MATERIALS AND METHODS: Rats were treated with one of the two regimens: one based on the typical neurotoxic regimen (4 x 10 mg/kg every 2 h) and one based on pharmacokinetic modeling (Cho AK, Melega WP, Kuczenski R, Segal DS Synapse 39:161-166, 2001) designed to better represent accumulating plasma concentrations of MA as seen in human users (24 x 1.67 mg/kg once every 15 min) matched for total daily dose. In two separate experiments, dosing regimens were compared for their effects on markers of neurotoxicity or on behavior. RESULTS: On markers of neurotoxicity, MA showed decreased dopamine (DA) and 5-HT, increased glial fibrillary acidic protein, and increased corticosterone levels regardless of dosing regimen 3 days post-treatment. Behaviorally, MA-treated groups, regardless of dosing regimen, showed hypoactivity, increased initial hyperactivity to a subsequent MA challenge, impaired novel object recognition, impaired learning in a multiple T water maze test of path integration, and no differences on spatial navigation or reference memory in the Morris water maze. After behavioral testing, reductions of DA and 5-HT remained. CONCLUSIONS: MA treatment induces an effect on path integration learning not previously reported. Dosing regimen had no differential effects on behavior or neurotoxicity.     

hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling

: The heparin-binding growth factors fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) are potent mitogens for hepatocellular carcinomas (HCCs). Heparin-binding growth factor signaling is regulated by sulfation of cell-surface heparan sulfate proteoglycans (HSPGs). We hypothesized that hSulf1, a recently described sulfatase, regulates growth signaling in HCCs. :Expression of hSulf1 in human HCC tumors was determined by real-time PCR. Down-regulation of hSulf1 expression was investigated by analyzing loss of heterozygosity (LOH) at the hSulf1 locus and the effect of the DNA methylation inhibitor 5-aza-deoxycytidine on hSulf1 expression. The subcellular location of hSulf1 and sulfation state of cell-surface HSPGs were assessed by immunocytochemistry. FGF and HGF signaling was examined by phospho-specific immunoblot analysis. Cell growth was measured by trypan blue exclusion, and the MTT assay and apoptosis were quantitated by fluorescence microscopy. :hSulf1 expression was decreased in 29% of HCCs and 82% of HCC cell lines. There was LOH at the hSulf1 locus in 42% of HCCs. Treatment with 5-aza-deoxycytidine reactivated hSulf1 expression in hSulf1-negative cell lines. Low hSulf1-expressing cells showed increased sulfation of cell-surface HSPGs, enhanced FGF and HGF-mediated signaling, and increased HCC cell growth. Conversely, forced expression of hSulf1 decreased sulfation of cell-surface HSPGs and abrogated growth signaling. HCC cells with high-level hSulf1 expression were sensitive to staurosporine- or cisplatin-induced apoptosis, whereas low expressing cells were resistant. Transfection of hSulf1 into hSulf1-negative cells restored staurosporine and cisplatin sensitivity. :Down-regulation of hSulf1 contributes to hepatocarcinogenesis by enhancing heparin-binding growth factor signaling and resistance to apoptosis.     

A Meta-Analysis of the Effect of Experimental Sleep Restriction on Youth’s Attention and Hyperactivity

This meta-analysis examined the effect experimental sleep restriction has on youth’s attention and hyperactivity outcomes. Thirteen published studies containing 17 independent samples were included (N = 496). Random- and fixed-effects models were used to estimate pooled effect sizes and moderator effects, respectively. Results indicate that sleep-restricted youth had significantly worse attention outcomes than youth with extended sleep, but no differences were evident regarding hyperactivity. Significant moderators of this effect included age and sex. These results have important implications for both the prevention and treatment of attention problems, highlighting the need for health professionals to screen for and treat underlying sleep issues.