Organisms Commons^™

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …

No Evidence For Kin Protection In The Expression Of Sickness Behaviors In House Mice, Patricia C. Lopes, Per Block, Alice Pontiggia, Anna K. Lindholm, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When infected, animals change their behaviors in several ways, including by decreasing their activity, their food and water intake, and their interest in social interactions. These behavioral alterations are collectively called sickness behaviors and, for several decades, the main hypotheses put forward to explain this phenomenon were that engaging in sickness behaviors facilitated the fever response and improved the likelihood of host survival. However, a new hypothesis was recently proposed suggesting that engaging in sickness behaviors may serve to protect kin. We tested this kin protection hypothesis by combining a field and a laboratory experiment in house mice. In both …

Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions.

Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis–Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot.

Microsomal CYP2D exhibited high affinity and low capacity, compared with the mitochondrial CYP2D that had a much lower (∼50-fold) affinity but a higher (∼six-fold) …

Exploring Stable Isotope Analysis For The Identification Of Prior Tick Hosts, Kiprian Gernat

Honors Theses

Lyme disease is a pervasive illness caused by the transmission of the spirochete Borrelia burgdorferi from the bite of an infected black-legged tick, Ixodes scapularis. Ticks initially obtain the spirochete by feeding on an infected animal host. Ticks feed on a broad range of hosts, but some of these hosts are more competent carriers of Lyme disease and more readily transmit B. burgdorferi to feeding ticks. Thus, knowing what host a tick has fed on could provide valuable information in studying the transmission of Lyme disease. However, studying the relationships between ticks and their hosts has proved to be …

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Lubo Zhang, PhD

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent the …

Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer

MSU Graduate Theses

Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, …

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. …

Innate Chemical Resistance Of Virginia Big-Eared Bats (Corynorhinus Townsendii Virginianus) To White-Nose Syndrome, Daniel S. Danford, Leah Shriver, Hazel A. Barton

Williams Honors College, Honors Research Projects

White-nose Syndrome (WNS) is an emergent epidemic disease of bats in North America. Caused by the novel fungal pathogen Pseudogymnoascus destructans, with a mortality rate of >75%, in the last decade WNS has led to the local extinction of numerous bat species. Despite this high mortality, one species, the Virginia big-eared bat (Corynorhinus townsendii virginianus) remains unaffected. Virginia big-eared bats (VBEs) are commonly found covered in a yellow, oily substance, with a pelage commensal population dominated by the yeast, Debaryomyces udenii. As D. udenii is an oleaginous yeast that produces yellow colonies, the fungus may be responsible …

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …