Are Prerequisite Courses Barriers to Pharmacy Admission or the Keys to Student Success?

The variability and complexity of course prerequisites across colleges and schools of pharmacy can result in barriers to admission. While prerequisites play an important role in the admissions process and assuring student preparation, requiring excessive prerequisites can create unnecessary challenges for applicants. Prospective students may choose not to apply to a particular pharmacy school or even enter the profession because they cannot complete all course prerequisites in time to apply.

Mood-stabilizing effects of rapamycin and its analog temsirolimus: relevance to autophagy.

Accumulated data support a relationship between mood disorders and cellular plasticity and resilience, some suggesting relevance to autophagy. Our previous data show that pharmacological enhancement of autophagy results in antidepressant-like effects in mice. The current study was designed to further examine the effects of autophagy enhancement on mood by testing the effects of subchronic treatment with the mammalian target of rapamycin (mTOR) inhibitors and autophagy enhancers rapamycin and temsirolimus in a model for mania and in a model for antidepressant action, respectively.

Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain.

Objectives: Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling.

Opioid prescribing patterns for non-malignant chronic pain for rural versus non-rural US adults: a population-based study using 2010 NAMCS data.

Background: Non-malignant chronic pain (NMCP) is one of the most common reasons for primary care visits. Pain management health care disparities have been documented in relation to patient gender, race, and socioeconomic status. Although not studied in relation to chronic pain management, studies have found that living in a rural community in the US is associated with health care disparities.

Fetal and neonatal iron deficiency exacerbates mild thyroid hormone insufficiency effects on male thyroid hormone levels and brain thyroid hormone-responsive gene expression.

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone.

Fetal and neonatal iron deficiency reduces thyroid hormone-responsive gene mRNA levels in the neonatal rat hippocampus and cerebral cortex.

Copper (Cu), iron (Fe), and thyroid hormone (TH) deficiencies produce similar defects in late brain development including hypomyelination of axons and impaired synapse formation and function, suggesting that these micronutrient deficiencies share a common mechanism contributing to these derangements. We previously demonstrated that fetal/neonatal Cu and Fe deficiencies lower circulating TH concentrations in neonatal rats. Fe deficiency also reduces whole-brain T(3) content, suggesting impaired TH action in the developing Fe-deficient brain.

Modeling mania: Further validation for Black Swiss mice as model animals.

The paucity of appropriate animal models for bipolar disorder hinders the research of the disorder and its treatments. Previous work suggests that Black Swiss (BS) mice may be a suitable model animal for behavioral domains of mania including reward-seeking, risk-taking, vigor, aggression and sensitivity to psychostimulants. These behaviors are high in BS mice compared with other strains and are responsive to the mood stabilizers lithium and valproate but not to the antidepressant imipramine.

Maternal iron supplementation attenuates the impact of perinatal copper deficiency but does not eliminate hypotriiodothyroninemia nor impaired sensorimotor development.

Copper, iron and iodine/thyroid hormone (TH) deficiencies disrupt brain development. Neonatal Cu deficiency causes Fe deficiency and may impact thyroidal status. One purpose of these studies was to determine the impact of improved iron status following Cu deficiency by supplementing the diet with iron.

Evidence of evolutionary conservation of function between the thyroxine transporter Oatp1c1 and major facilitator superfamily members.

Organic anion transporting polypeptide 1c1 (Oatp1c1) is a high-affinity T(4) transporter expressed in brain barrier cells. To identify Oatp1c1 amino acid residues critical for T(4) transport, consensus membrane topology was predicted and a three-dimensional Oatp1c1 structure was generated using the known structures of major facilitator superfamily (MFS) transporters, glycerol 3-phosphate transporter, lactose permease, and the multidrug transporter Escherichia coli multidrug resistance protein D as templates. A total of nine amino acid mutations were generated based on amino acid conservation, localization to putative transmembrane domains, and side chain functionality.

Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations.

Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate.

Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis.

Thyroid hormone (TH) induces the dramatic morphological and physiological changes that together comprise amphibian metamorphosis. TH-responsive tissues vary widely with developmental timing of TH-induced changes. How larval tadpole tissues are able to employ distinct metamorphic programs in a developmental stage- and TH-dependent manner is still unknown.

Novel and emerging strategies in drug delivery for overcoming the blood-brain barrier.

Two decades of molecular research have revealed the presence of transporters and receptors expressed in the brain vascular endothelium that provide potential novel targets for the rational design of blood-brain barrier-penetrating drugs. In this review, we briefly introduce the reader to the molecular characteristics of the blood-brain barrier that make this one of the most important obstacles towards the development of efficacious CNS drugs. We highlight recent attempts to rationally target influx and bidirectional transport systems expressed on the brain endothelial cell and avoid the important obstacle presented in the form of efflux transporters.

The blood-brain barrier thyroxine transporter organic anion-transporting polypeptide 1c1 displays atypical transport kinetics.

Organic anion-transporting polypeptide (Oatp) 1c1 is a high-affinity T(4) transporter expressed in brain barrier cells. Oatp1c1 transports a variety of additional ligands including the conjugated sterol estradiol 17beta-glucuronide (E(2)17betaG). Intriguingly, published data suggest that E(2)17betaG inhibition of Oatp1c1-mediated T(4) transport exhibits characteristics suggestive of atypical transport kinetics.

The Thrsp null mouse (Thrsp(tm1cnm)) and diet-induced obesity.

We created a Thrsp (Spot 14 or S14) null mouse (Thrsp(tm1cnm)) to study the role of Thrsp in de novo lipid synthesis. The Thrsp null mouse exhibits marked deficiencies in de novo lipogenesis in the lactating mammary gland. We now report the Thrsp gene deletion affects body weight and glucose tolerance associated with increased insulin sensitivity.

Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs.

Organic anion transporting polypeptide (Oatp) 1c1 is a high-affinity T(4) transporter with narrow substrate specificity expressed at the blood-brain barrier. A transport model using cells overexpressing Oatp1c1 was created to identify novel Oatp1c1 substrates and inhibitors. Rat Oatp1c1 was cloned and stably expressed in human embryonic kidney 293 cells.

Hepatic expression of the SPOT 14 (S14) paralog S14-related (Mid1 interacting protein) is regulated by dietary carbohydrate.

The Spot 14 (S14) gene is rapidly up-regulated by signals that induce lipogenesis such as enhanced glucose metabolism and thyroid hormone administration. Previous studies in S14 null mice show that S14 is required for normal lipogenesis in the lactating mammary gland, but not the liver. We speculated that the lack of a hepatic phenotype was due to the expression of a compensatory gene.

Thyroid hormone and cerebellar development.

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development.

Organic anion-transporting polypeptides at the blood-brain and blood-cerebrospinal fluid barriers.

Organic anion-transporting polypeptides (Oatps) are solute carrier family members that exhibit marked evolutionary conservation. Mammalian Oatps exhibit wide tissue expression with an emphasis on expression in barrier cells. In the brain, Oatps are expressed in the blood-brain barrier endothelial cells and blood-cerebrospinal fluid barrier epithelial cells.

The Spot 14 protein is required for de novo lipid synthesis in the lactating mammary gland.

We generated a Spot 14 null mouse to assess the role of Spot 14 in de novo lipid synthesis and report the Spot 14 null mouse exhibits a phenotype in the lactating mammary gland. Spot 14 null pups nursed by Spot 14 null dams gain significantly less weight than wild-type pups nursed by wild-type dams. In contrast, Spot 14 null pups nursed by heterozygous dams show similar weight gain to wild-type littermates.

Thyroid hormone regulates oligodendrocyte accumulation in developing rat brain white matter tracts.

Thyroid hormone (TH) is necessary for normal axonal myelination. Myelin basic protein (MBP) is a structural protein essential for myelin function. In this study, we demonstrate that perinatal hypothyroidism regulates MBP mRNA levels via indirect mechanisms.

Control of thyroid hormone action in the developing rat brain.

Thyroid hormones play important roles in brain development. The physiologic function of thyroid hormones in the developing brain is to provide a timing signal that leads to the induction of differentiation and maturation programs during precise stages of development. Inappropriate initiation of these timing events leads to asynchrony in developmental processes and a deleterious outcome.

Human spot 14 glucose and thyroid hormone response: characterization and thyroid hormone response element identification.

Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity.

A novel dynamin III isoform is up-regulated in the central nervous system in hypothyroidism.

Hypothyroidism in early postnatal development leads to abnormal CNS development that may be controlled in part at the level of gene transcription. Comparing the expression of euthyroid (EuT) and hypothyroid (HypoT) rat brain mRNAs by differential display PCR (ddPCR), we identified a novel dynamin III mRNA that was up-regulated in the hypothyroid state. Northern analysis of brain mRNA using a probe from the dynamin III open reading frame (ORF) revealed two transcripts of 3.

Triiodothyronine is a survival factor for developing oligodendrocytes.

Thyroid hormone plays an important role in oligodendrocyte development. The studies presented here suggest that thyroid hormone is required for oligodendrocyte survival during development. Oligodendrocyte precursor cells, astrocytes and microglia were cultured in a defined media.