Caring for our own: the role of institutionalized support structures in Native American nursing student success

In this project, the authors asked 19 Native American baccalaureate nursing students to discuss their experiences with a formal institutionalized student support program called "Caring for Our Own: A Reservation/University Partnership Program." The authors investigated the importance of different types of support structures within this program, as viewed by Native American nursing students. They distinguished between four institutionalized support structures: tangible, informational, emotional, and belonging. The authors found that students consider tangible support (such as stipends) to be comparatively less important than other types of support, particularly emotional and belonging support. Responses also revealed the importance of a fifth type of institutionalized support-motivational. The authors further discuss how these institutionalized support structures might lead to successful outcomes for Native American nursing students.     

Characterization and Quantitation of Aggregates and Particles in Interferon-β Products: Potential Links Between Product Quality Attributes and Immunogenicity

Interferon- β (IFN-β) products have been used for many years in the treatment of multiple sclerosis and include recombinant IFN-β-1b (Betaseron®) and IFN-β-1a (Avonex® and Rebif®). All three products lead to the formation of neutralizing antibodies (NAbs) and resulting loss of efficacy in patients but to different extents. Across several clinical trials, the reported rates ofneutralizing-antibody formation were 22%–47% (Betaseron®), 5%–35% (Rebif®), and 2%–13% (Avonex®). In the current study, all products were purchased from the pharmacy and aggregates were characterized and/or quantified using size-exclusion chromatography (SEC), analytical ultracentrifugation, gel electrophoresis, and dot-blotting immunoassays. Particle characterization and counting were performed using microflow imaging, particle tracking analysis, and resonant mass measurement. Betaseron® and Rebif®, which are formulated with human serum albumin, had the greatest amount of aggregated protein and particles (e.g., 9%–15% high molecular weight species by SEC and > 100,000 particles/mL by flow imaging). Avonex® was found to have the least amount of aggregated protein, with > 95% monomer content by both SEC and analytical ultracentrifugation, and the particles detected in Avonex® were determined to be primarily silicone oil droplets. These results strongly suggest that protein aggregate and particle contents are key product quality attributes in a given product’s propensity to elicit the production of NAbs in patients. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:915–928, 2013     

TGFbeta1 deficiency does not affect the generation and maintenance of CD4+CD25+FOXP3+ putative Treg cells, but causes their numerical inadequacy and loss of regulatory function

TGFbeta1 is considered to be required for peripheral maintenance of CD4(+)CD25(+)FOXP3(+) T(reg) cells. However, we demonstrate no reduction in the percentage of such T cells in the spleens and thymi of Tgfb1(-/-) mice. Although putative T(reg) cells, characterized as CD4(+)CD25(+)FOXP3(+)CD62L(+) T cells, are increased in Tgfb1(-/-) mice, they may be inadequate to control activated T cells since the ratio of activated T cells:putative T(reg) cells is several-fold higher in Tgfb1(-/-) mice than in control mice. We further show that whereas Tgfb1(-/-) mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in putative T(reg) cells, there are no detectable CD4(+)CD25(+) T cells in the spleens of DO11.10 Rag1(-/-) mice suggesting that T(reg)-cell generation is self-antigen dependent regardless of whether they express Tgfb1. Finally, we demonstrate that Tgfb1(-/-) T cells remain responsive to the suppressive effect of TGFbeta1 in vitro. These data suggest that TGFbeta1 is required for the regulatory function of T(reg) cells to prevent activation of T cells and autoimmunity.     

Fine structure of hepatocytes from fasted and fed rats

The fine structure of hepatocytes from rats maintained on a controlled feeding schedule are described. Liver samples were processed for electron microscopy, histochemistry and chemical determinations of glycogen at precise time-intervals following a 30-hour fast and a 2-hour meal. Hepatocytes from 30-hour-fasted rats with extremely low hepatic glycogen levels were devoid of glycogen particles. Centrilobular cells showed areas of the cytoplasm rich in vesicles of smooth endoplasmic reticulum (SER) while periportal hepatocytes contained less extensive regions of SER. Soon after feeding the fasted rats, glycogen particles appeared in regions of the cell rich in SER. Centrilobular hepatocytes contained numerous glycogen areas which were infiltrated with tubules of SER, while periportal cells showed dense glycogen deposits with SER restricted to the periphery of the masses of glycogen. Throughout glycogen deposition each glycogen particle was closely associated with membranes of SER until maximum glycogen deposition was achieved 12 hours after initiation of feeding. At this point SER was reduced to the lowest amounts of the time-periods studied. During stages of glycogen depletion SER proliferated and reached the highest concentration measured in this study. Tubules of SER were present throughout the glycogen masses of centrilobular hepatocytes, whereas in periportal cells the organelle was restricted to the periphery of the glycogen masses. It is concluded that SER is associated with glycogen particles in rat hepatocytes during both deposition and depletion of glycogen.     

Distribution and function of angiotensin II receptors in mouse spermatozoa.

Previous work indicates that angiotensin II (AngII) stimulates sperm motility and acrosomal exocytosis. Here we determined the distribution of AngII receptors on mouse sperm by immunocytochemistry and used Ca2+ probe photometry to examine their coupling to sperm regulatory pathways. We found both AT1 and AT2 receptors localized on the acrosomal region of the sperm head. The AT1 receptor, but not the AT2 receptor, is found also on the principal piece of the sperm tail. Local perfusion of motile but nonprogressive sperm with 0.1-1 microM of AngII evokes a rapid, substantial rise in intracellular [Ca2+]. This response is blocked by losartan, a specific antagonist of the AT1 receptor. These results indicate that sperm possess functional AT1 receptors that are distributed to sites that may allow selective control of motility and exocytosis. They also suggest that the AT2 receptors detected by immunoreactivity are either nonfunctional or are not coupled to Ca(2+)-mediated signalling mechanisms.     

hERGCentral: a large database to store, retrieve, and analyze compound-human Ether-à-go-go related gene channel interactions to facilitate cardiotoxicity assessment in drug development

The unintended and often promiscous inhibition of the cardiac human Ether-à-go-go related gene (hERG) potassium channel is a common cause for either delay or removal of therapeutic compounds from development and withdrawal of marketed drugs. The clinical manifestion is prolongation of the duration between QRS complex and T-wave measured by surface electrocardiogram (ECG)-hence Long QT Syndrome. There are several useful online resources documenting hERG inhibition by known drugs and bioactives. However, their utilities remain somewhat limited because they are biased toward well-studied compounds and their number of data points tends to be much smaller than many commercial compound libraries. The hERGCentral ( www.hergcentral.org ) is mainly based on experimental data obtained from a primary screen by electrophysiology against more than 300,000 structurally diverse compounds. The system is aimed to display and combine three resources: primary electrophysiological data, literature, as well as online reports and chemical library collections. Currently, hERGCentral has annotated datasets of more than 300,000 compounds including structures and chemophysiological properties of compounds, raw traces, and biophysical properties. The system enables a variety of query formats, including searches for hERG effects according to either chemical structure or properties, and alternatively according to the specific biophysical properties of current changes caused by a compound. Therefore, the hERGCentral, as a unique and evolving resource, will facilitate investigation of chemically induced hERG inhibition and therefore drug development.     

Nonepileptic seizures treatment workshop summary

In May 2005, an international, interdisciplinary group of researchers gathered in Bethesda, MD, USA, for a workshop to discuss the development of treatments for patients with nonepileptic seizures (NES). Specific subgroup topics that were covered included: pediatric NES; presenting the diagnosis of NES, outcome measures for NES trials; classification of NES subtypes; and pharmacological treatment approaches and psychotherapies. The intent was to develop specific research strategies that can be expanded to involve a large segment of the epilepsy and psychiatric treatment communities. Various projects have resulted from the workshop, including the initial development of a prospective randomized clinical trial for NES.