Persistent and uncontrolled inflammation is the root cause of various debilitating diseases. Given that interleukin-1 receptor–associated kinase 4 (IRAK4) is a critical modulator of inflammation, inhibition of its activity with selective drug molecules (IRAK4 inhibitors) represents a promising therapeutic strategy for inflammatory disorders. To exploit the full potential of this...
The gut microbiome has been previously implemented in a number of diseases. Of note is its substantial role in metabolic syndrome, which encapsulates a group of conditions that increase the risk of cardiovascular disease, type 2 diabetes, and stroke. Understanding the causal relationships between the gut microbiome and host processes...
Natural products have long been an important source of resources for humans. Many of these compounds possess unique chemical structures and potent biological properties. By targeting natural products with specific chemical properties, we can gain a better understanding of the roles these compounds play in the environment and their interactions...
Natural products (a.k.a. secondary metabolites) are produced by living organisms that are not essential for their growth, development, or reproduction, but may play a role in their survival or adaptability in nature. Many secondary metabolites isolated from plants and microbes have found use as molecular probes, drug leads, or medicine...
Nucleic acid therapeutics has cemented itself as one of the most efficacious and robust avenues for treatment of a wide range of diseases from vaccine development to treatment of liver, retina, cancer applications. Non-viral mediated gene delivery using lipid-based nanoparticle (LNP) carriers has proven its compatibility with addressing unexpected, fast...
Since the discovery of penicillin in 1928, the fungal kingdom has remained a fertile source for the discovery of new, biologically active, natural products. Further, as natural products continue to be discovered from fungi, a deeper understanding of the critical role of specialized metabolism in fungal ecology is afforded. The...
In the United States, the wild horse population exceeds the recommended carrying capacity by about 60,000 horses.
• Current contraceptive methods include: surgical (removal of ovaries), hormonal (progesterone, GnRH), and immunologic (porcine zona pellucida, GnRH).
• SPACA3 is a sperm surface membrane protein involved in sperm-egg plasma membrane adhesion and...
Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g.,...
Messenger RNA (mRNA) therapy has massive potential to treat various genetic disorders by providing effective proteins to the diseased cells and tissues. Its therapeutic applications include protein replacement, genome editing, and immunotherapy. For successful mRNA treatment, mRNA must be delivered to the cytosol of target cells. One of the leading...
Curbing overall disease burden with faster intervention requires early stage and accurate diagnostics. Ultrasound (US) provides a safe, nonionizing, inexpensive, and noninvasive imaging modality that has become commonplace in diagnostics. Paired with the relatively new technology of photoacoustic imaging (PAI), optical level resolution becomes feasible with the deeper signal penetration...
Ribomimetic natural products have long been known for their important biological activities. Structurally, they contain a densely functionalized cyclopentane unit that resembles ribose. Pactamycin, the prominent member of this class of natural products, is a potent protein synthesis inhibitor produced by the soil bacterium Streptomyces pactum. In pactamycin, the aminocyclopentitol...
Among the myriad of natural products are pseudosugar-containing secondary metabolites, e.g., the C7-pseudosugar-containing oligosaccharide acarbose, the C6- pseudosugar-containing aminoglycoside antibiotics, and the five-membered ring pseudosugar-containing antibiotic pactamycin. The C7-pseudosugars are normally derived from sedoheptulose 7-phosphate catalyzed by a family of enzymes called sedoheptulose 7-phosphate cyclases (SH7PCs). This family of enzymes...
Obesity is a complex multifactorial disease resulting from excessive energy intake compared to energy expenditure. The excess energy is mostly stored as fat in enlarged adipocytes, but some lipids may infiltrate other organs such as the liver to form ectopic fat. Adipose tissue and ectopic fat produce and secrete a...
Linden (Tilia spp.), a profusely flowering temperate tree that provides bees with vital pollen and nectar, has been associated with bumble bee (Bombus spp.) mortality in Europe and North America. Bee deaths have been attributed, with inadequate evidence, to toxicity from mannose in nectar or starvation due to low nectar...
Polyphenolic compounds found in foods such as fruits, vegetables, legumes, nuts and grains, are an integral part of the human diet. Within polyphenols, proanthocyanidins are referred to as condensed tannins and encompass procyanidins, propelargonidins and prodelphinidins. Among these, procyanidins are the largest group. Recent interest in these compounds is related...
Ewing sarcoma (EwS) is the second most highly malignant tumor that arises mainly from bone and surrounding soft tissue of adolescent and young adult patients. Despite the advances in Ewing sarcoma treatment that today include a combination of five chemotherapeutic agents, surgery, and/or radiotherapy, these therapies have demonstrated limited improvement...
The draft genome of Streptomyces sp. strain ventii, an environmental isolate recovered from deep-sea hydrothermal vents in the Pacific Ocean, is presented along with the resequenced draft genomes of the type strains Streptomyces bohaiensis 11A07 and Streptomyces lonarensis NCL 716.
Vitiligo is a disease characterized by depigmented patches of skin. The disease is known to involve the loss of melanocytes in the basal layer of the skin in affected areas, but the underlying mechanisms are unknown. Recent evidence suggests oxidative stress and disruptions to antioxidant pathways contribute to an autoimmune...
Superwarfarins are anticoagulant rodenticides that are 100 times more potent and 15 times more persistent than warfarin. They have been used since the 1980s and cause over 10,000 cases of accidental and intentional poisonings per year. Apart from inducing uncontrollable bleeding, by inhibiting the vitamin K cycle, superwarfarins can disrupt...
Popular botanical dietary supplements marketed for management of menopausal symptoms, including hops (Humulus lupulus L.), red clover (Trifolium pratense) and licorice (Glycyrrhiza uralensis), were evaluated for their potential to alter CYP-mediated drug metabolism clinically and pre-clinically. Both hops and red clover had been reported to inhibit certain cytochrome P450 (CYP)...
The potential for nanomedicine to reduce toxicity and improve therapeutic response to radiation is vast. Clinically, this potential has thus far only begun to be realized with the recent success of the radioenhancing nanoparticle, NBTXR3 by Nanobiotix. Radioenhancing nanoparticles, however, represent only a small class of nanomaterials that may be...
Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the...
Nearly 80% of solid tumors, such as melanoma, metastasize via the lymphatic system. The most common form of melanoma is BRAF-mutant melanoma, and additional mutations, such as a PTEN mutation in the PI3K pathway, is required for metastases to occur. Standard therapy includes treatment with small molecules dabrafenib (DAB) and...
Intracellular delivery of mRNA holds great potential for vaccine and therapeutic discovery and development. This is realized by the preeminent role mRNA is playing in the record-breaking pace of SARS-CoV-19 vaccine development. Recent advances in chemical modifications of mRNA have enabled high-efficiency gene expression with superior spatiotemporal control while eliminating...
This thesis describes in-vitro and in-vivo evaluation of a transdermal atenolol formulation developed at Oregon State University, College of Pharmacy. The formulation was prepared from carbomer as a gel base with propylene glycol, glycerol, ethanol, polysorbate 80 and dimethyl-isosorbide (DMI) as mixture of penetration enhancing agents. The effect of the...
Utilizing nanocarrier based drug delivery for improving the magnitude of efficacy of chemotherapeutic agents in many diseases has acquired more attention in research applications. It has shown promising results in both preclinical and clinical trials. The Food and Drug Administration (FDA) has approved many of these polymeric carriers, and tens...
This data contains large supplementary tables for the PhD dissertation of Dariia Vyshenska. Title of the Dissertation: "Identification of Cervical Cancer Key Regulators using Network Biology Approach"
The dataset contains data from two types of research.
Research #1: Identification of bacterial regulators of cervical cancer gene expression. It contains microbial...
Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause of the disease. Currently available treatment methods are limited and emphasize the need for discovery of new therapies that improve patient outcome. Chromosomal amplifications have been identified as a source of...
Despite advances in treatment, cancer remains among the leading causes of death in the world. Progress in the treatment of metastatic cancers was seen with chemotherapy and radiotherapy, however, the major drawbacks of conventional cancer therapies are limited efficacy and severe side effects. Magnetic fluid hyperthermia (MFH) is a new...
Sugar phosphate cyclases (SPCs) are enzymes involved in the biosynthesis of many important natural products. SPCs form a unique cyclitol during the early steps in the biosynthesis of many natural products. These natural products include rifamycin, which is chemically modified to rifampicin and used clinically as an antituberculosis drug, and...
Marine natural products possess an abundance of diverse chemical scaffolds with unique biological activities. By targeting unusual or unique microbial environments within varying marine ecologies we can continue to discover novel chemistry with potentially new molecular targets. The research presented here is focused on exploring unusual chemical ecologies and the...
Leukemogenesis, uncontrolled proliferation of dysfunctional, transformed immature lymphocytes, appears, especially in children, to be associated with abrogation of normal lymphopoiesis, and thymopoiesis in the case of T cell leukemias. Sequence specific transcription factors (SSTFs) are nuclear control switches that respond to cellular signals to alter cell state and cell fate...
The methodology to perform bioequivalence studies for prodrug products has not been finalized by FDA leaving the investigators to speculate over the proper approach. This study innovatively utilized the bootstrap methods for testing in vivo bioequivalence on both parent drug and metabolite of four prodrug products: Clopidogrel, Prednisone, Allopurinol, and...
Cancer is the second leading cause of death in the United States. To date, over 60% of current anticancer drugs were inspired by the discovery of chemical structure from nature, commonly known as a natural product. This work represents the biological characterization of several marine natural product compounds and their...
Neisseria gonorrhoeae is the sexually transmitted pathogen responsible for millions of cases of gonorrhea worldwide each year. Rapidly-spreading antibiotic resistance is diminishing the ability to effectively treat a disease with significant consequences to female and male reproductive health, as well as to neonatal well-being. A protective vaccine has the potential...
Ovarian cancer, “the silent killer,” is one of the deadliest gynecological diseases due to delayed diagnosis, leading to a heavily disseminated and aggressive metastatic cancer. Therapeutic options are limited at stages III-IV of ovarian cancer, in which debulking surgery and cytotoxic chemotherapy remain the mainstays of
intervention. However, these therapeutic...
TAC is the most commonly used medication in post transplantation maintenance immunosuppression therapy. TAC lipophilicity and its erratic oral absorption especially in the presence of food intake result in great intra- and interpatient pharmacokinetic variations. Complicated dosing and frequent required therapeutic monitoring is thought to be the main cause of...
Skeletal muscle is the largest organ in the body by mass, comprising roughly 40% of total bodyweight in adults. It plays diverse and unique roles that include movement, locomotion, and support for posture and internal organs, among others. The structural foundation for all skeletal muscle in adults is formed early...
Foot pathology is a real problem in captive elephants. Osteoarthritis is the major concern among musculoskeletal disorders and foot health problems for elephants in North America zoos with one-‐half of Elephants in captivity showing foot health care problems in zoos. A higher ratio of captive Asian elephants (Elephas maximus) is...
Pactamycin, a potent antitumor antibiotic produced by the soil bacterium Streptomycespactum, is a structurally unique aminocyclopentitol-containing natural product. Itconsists of a highly functionalized cyclopentitol core unit, two aromatic rings [3-aminoacetophenone (3AAP) and 6-methylsalicylic acid (6MSA)], and a 1,1-dimethylurea moiety. Despite its potent biological activity, the development of thisantibiotic was hampered...
The discovery of new antibiotics reached its peak during the golden era of antibiotics in the mid 20th century and continued to thrive until the 1980s. However, after more than 50 years of fruitful exploration and exploitation of microbial natural products the discovery rate of new antibiotics has dropped drastically...
This thesis describes an investigation of the natural products chemistry of two fungal species of the genus Tolypocladium. Natural products are small organic molecules that are considered non-essential for cell growth and reproduction, and thus part of secondary metabolism. Chemical profiling of these secondary metabolites using a combination of high-performance...
Our quest for pharmaceutically important marine natural products led to re-isolation of known mandelalides A-D and identification of new congeners E-L from re-collected South African Lissoclinum tunicate specimens. Mandelalides A, B, and L were characterized as selective cancer cell toxins, with an unusual activity profile influenced by their glycosylation /...
Mammalian skin is the largest organ of the body and serves as a barrier to protect the body against chemical, mechanical and pathogenic insults as well as water loss. The epidermis is formed from the primitive ectoderm into a multilayered stratified epithelium, consisting of basal, spinous, granular and outermost cornified...
The sexually transmitted disease gonorrhea, caused by the Gram-negative bacterium and obligate human pathogen Neisseria gonorrhoeae, remains a significant health and economic burden worldwide. In the absence of a protective vaccine, antimicrobial agents are the only pharmacological intervention for patients with gonorrhea. However, due to the remarkable ability of gonococcus...
Despite the advance of biomedical science, infectious diseases remain one of the number one killers in the world. They claim the lives of millions of people annually, particularly in underdeveloped and developing countries. In fact, more than 32% of the health burden in Africa is caused by infectious diseases, e.g.,...
ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Poor aqueous solubility of a large number of newly discovered chemical entities is posing a significant challenge for the formulation industry and is delaying their drug development. The number of formulation techniques available to solubilize these poorly soluble molecules is very limited. In addition to that, traditional formulation methods involve...
BCL11B, a gene regulatory transcription factor, is known to be a regulator of T cell development in the immune system, and has been identified as a tumor suppressor for T cell leukemias. Defining the molecular events that regulate the activity of BCL11B will provide potential drug targets that will aid...
Natural products from both terrestrial and marine sources represent a significant source of novel drug leads, and have previously been developed into clinically-approved agents for the treatment of various human diseases. This work represents the biological characterization of the mechanistic basis for activity of several natural product structures in models...
Image-guided phototherapy is extensively considered as a promising therapy for cancer treatment. To enhance translational potential of this modality, we developed a single agent-based biocompatible nanoplatform that provides both real time near-infrared (NIR) fluorescence imaging and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms. The developed theranostic nanoplatform consists...
Background:
Neisseria gonorrhoeae (GC) is a Gram-negative pathogen that most commonly infects mucosal surfaces, causing sexually transmitted urethritis in men and endocervicitis in women. Serious complications associated with these infections are frequent and include pelvic inflammatory disease, ectopic pregnancy, and infertility. The incidence of gonorrhea cases remains high globally while...
Five cases of bacterial meningitis treated with ceftaroline (4 Streptococcus pneumoniae and 1 Staphylococcus aureus) are summarized here. The pharmacodynamics of human cathelicidin LL-37 and ceftaroline were evaluated against S. pneumoniae. Patients who received ceftaroline 600 mg every 8 h (q8h) (1 S. aureus and 3 S. pneumoniae) were successfully...
Clostridium perfringens is a spore-forming pathogenic bacterium that causes a variety of diseases in human and animals. C. perfringens type A isolates produce enterotoxin (CPE) causing food poisoning (FP) and non-food-borne (NFB) gastrointestinal (GI) diseases including antibiotic-associated diarrhea and sporadic diarrhea. C. perfringens type A food poisoning currently ranks as...
Perinatal growth restriction programs higher risk for chronic disease during adulthood via morphological and physiological changes in organ systems. Perinatal growth restriction is highly correlated with a decreased nephron number, altered renal function and subsequent hypertension. I hypothesize that such renal maladaptations result in altered pharmacologic patterns for life. Pregnant...
This thesis describes an investigation of the molecular basis of the substrate specificity and catalytic mechanism of a unique pseudoglycosyltransferase (PsGT) enzyme, VldE. PsGTs are a newly discovered group of glycosyltransferase (GT)-like proteins that catalyze the transfer of a pseudosugar to an acceptor molecule via a C-N bond formation. This...
Gene regulatory networks are commonly used for modeling biological processes and revealing underlying molecular mechanisms. The reconstruction of gene regulatory networks from observational data is a challenging task, especially considering the large number of players (e.g. genes) involved and the small number of biological replicates available for analysis. Herein, we...
Phospholipase C enzymes hydrolyze the rare membrane lipids phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) PIP into inositol triphosphate (IP3) and diacylglycerol (DAG). Phospholipase C enzymes of the β subtype (PLC-β) function specifically in the signal transduction pathways regulated by Gαq-coupled seven transmembrane receptors. These signaling pathways link plasma membrane receptor activation...
Poly(ethylene glycol)-block-poly(aspartate-hydrazide) (PEG-p(Asp-Hyd)) was modified using either levulinic acid (LEV) or 4-acetyl benzoic acid (4AB) attached via hydrazone bonds. Paclitaxel (PTX) conjugated to the linkers formed PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX). PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) assemble into unimodal polymeric micelles with diameters of 42 nm and 137 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) at...
Microbial natural products represent a massive repository of unique chemical scaffolds with corresponding diverse biological functions. However, in the past decade the development of natural products into new therapeutics has dwindled, in part due to the challenges posed by high rediscovery rates and low throughput associated with classical bioassay-guided fractionation...
Coibamide A is a highly methylated cyclic depsipeptide isolated from Panamanian marine filamentous cyanobacteria as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. This structurally unique agent exhibits potent cancer cell toxicity with an unprecedented selectivity profile in the National Cancer Institute (NCI) 60 cell line...
Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus,
some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model
predicts that phytopathogenic isolates require a cluster of three loci present on a linear plasmid, with...
This work sought to characterize a link between Vitamin C and nitroglycerin at the level of enzymatic bioactivation. Before we could proceed, we needed to develop a method that sensitively and selectively identified the product of bioactivation, nitrite. We successfully adapted traditional diaminonaphthalene derivatization with the use of stable isotope...
Understanding the molecular mechanisms of ultraviolet (UV) induced melanoma formation is becoming crucial with more reported cases each year. Expression of type II nuclear receptor Retinoid-X-Receptor α (RXRα) is lost during melanoma progression in humans. Here, we observed that in mice with melanocyte-specific ablation of RXRα and RXRβ, melanocytes attract...
We compared uropathogen antibiotic susceptibility across age groups of ambulatory
pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant
differences (p<0.05) existed across age groups for ampicillin, cefazolin, and
trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in
trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88%...
OBJECTIVE: To establish a statewide network to detect, control, and prevent the spread of carbapenem-resistant Enterobacteriaceae (CRE)
in a region with a low incidence of CRE infection.
DESIGN: Implementation of the Drug Resistant Organism Prevention and Coordinated Regional Epidemiology (DROP-CRE) Network.
SETTING AND PARTICIPANTS: Oregon infection prevention and microbiology laboratory...
OBJECTIVE: The 75% of older adults with multiple chronic conditions are at risk of therapeutic competition (i.e. treatment for
one condition may adversely affect a coexisting condition). The objective was to determine the prevalence of potential
therapeutic competition in community-living older adults.
METHODS: Cross-sectional descriptive study of a representative sample...
BCL11B is a transcriptional regulatory protein that plays essential roles during mouse embryonic development. BCL11B is expressed and functions in the immune and nervous systems as well as within ectodermal organs. Multiple studies have characterized the roles of BCL11B in T cells, brain, and skin. However, very little is known...
Background: Medication complexity is a large determinant of adherence. Few studies have explored the relationship between cognitive impairment and medication complexity.
Objective: To evaluate whether cognitive impairment is associated with medication complexity for prescription and over-the-counter (OTC) medications.
Methods: In this cross-sectional analysis, we studied the association between cognitive impairment...
Context: Antibiotic prescribing in hospice patients is complicated by the focus on palliative rather than curative care and concerns regarding increasing antibiotic resistance.
Objective: To estimate antibiotic use in a national sample of hospice patients and identify facility and patient characteristics associated with antibiotic use in this population.
Methods: This...
Organismal development requires a precisely orchestrated transcriptional program to correctly deploy genetic information into the genome. This process requires sophisticated gene regulatory networks at multiple spatial and temporal levels from early embryonic development to adult physiological conditions. Molecular differences that define cell types are set up during the pattern formation...
The decrease in proline transport by the proline porter ProP in a Delta proQ strain has been well documented; however, the reason for this phenotype remains undefined. Previous studies have speculated that ProQ facilitates translation of proP mRNA. Here, we demonstrate that ProQ is enriched in the polysome fractions of...
Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-
resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at>6 mg/kg of body weight/day may be used
to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin)
therapy (>6...
The ascomycete fungus Tolypocladium inflatum, a pathogen of beetle larvae, is best known as the producer of the immunosuppressant drug cyclosporin. The draft genome of T. inflatum strain NRRL 8044 (ATCC 34921), the isolate from which cyclosporin was first isolated, is presented along with comparative analyses of the biosynthesis of...
A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells...
Metabolomics is a comprehensive analysis of small molecules, or metabolites, in a system. Metabolomics is a hypothesis-generating experiment and offers an unbiased analysis of cell metabolism that can aid in the understanding of fundamental biological processes. Metabolomics is widely and broadly applicable in the biological sciences and has been used...
Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses...
Background: Academic medical centers are examining relationships with the pharmaceutical industry
and making changes to limit interactions. Most doctors, however, practice outside of academic institutions
and see pharmaceutical detailers and accept drug samples and gifts. Little guidance for practicing
physicians exists about transforming practices to become pharma-free. Consideration must be...
OBJECTIVE. To quantify the association between admission to an intensive care unit (ICU) room most recently occupied by a patient positive for extended-spectrum beta-lactamase (EBSL)-producing gram-negative bacteria and acquisition of infection or colonization with that pathogen.
DESIGN. Retrospective cohort study.
SETTING AND PATIENTS. The study included patients admitted to medical...
Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative...
The nonproteinogenic amino acid enduracididine is a critical component of the mannopeptimycins, cyclic glycopeptide antibiotics with activity against drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus. Enduracididine is produced in Streptomyces hygroscopicus by three enzymes, MppP, MppQ, and MppR. On the basis of primary sequence analysis, MppP and MppQ are pyridoxal 5'-phosphate-dependent...
The level of postganglionic sympathetic nerve activity is
important in determining the tone of vascular smooth muscle, and
subsequent maintenance of normal blood pressure. It is generally
agreed that receptors located on postganglionic nerve terminals
(pre-junctional alpha₂ receptors) are important in the modulation of
neurotransmitter (norepinephrine) release from these nerves....
Dyphylline has been shown to be rapidly and completely
absorbed from oral tablets in an absolute bioavailability
study. In a pilot study two healthy male subjects received
1000 mg of dyphylline via intravenous infuson at a rate of
50 mg/min (1.0 ml/min) for 20 minutes. Plasma samples were
collected for...
The effects of L-ascorbic acid, thiamine HC1, or L-cysteine on
acetaldehyde blood levels and disposition were investigated in acetaldehyde-
treated rats. Rats were treated with ascorbic acid (2
mmoles/kg), thiamine (0.24 mmole/kg), or cysteine (2 mmoles/kg) one
hour before the administration of acetaldehyde (6 mmoles/kg). The
results show that each...
Propionic acid, live Propionibacterium shermanii, and
Dimethyl Fumarate (DMF) were tested for their stimulatory or
inhibitory efects on yeast, bacteria, and molds. The amount
of propionic acid required for inhibition of molds was
strain specific and equal to or less than that required for
inhibition of the yeasts. Live P....
Product formulation and in vitro dissolution characteristics of sustained-release chewable tablet dosage
forms are presented in chapter one of this thesis. In vivo
single dose and multiple dose studies of two
sustained-release formulations as well as one conventional
dyphylline formulation are described in chapter two. The
pharmacokinetics of dyphylline following...
Pharmacokinetics of theophylline and N-7 substituted
theophylline in rabbits when administered alone and in
various combinations were investigated. This thesis has
four chapters dealing with etophylline and theophylline;
proxyphylline and theophylline; dyphylline and theophylline;
and etophylline, proxyphylline and dyphylline pharmacokinetics
when administered concomitantly. All chapters
are interrelated. Each chapter has...
BCNU caused severe cholestasis in rats after a single intraperitoneal injection. The cholestasis was characterized by a selective reduction of the bile salt independent bile flow to 11% of control. Decreased food or water consumption by the treated rats apparently did not contribute to cholestasis. Measurements of plasma Na⁺ and...
Nalidixic acid and its derivatives act through inhibition of
bacterial DNA gyrase activity. Recently there have been a series of
papers reporting the antibacterial activity against three different
types of bacteria (S. aureus, E. coli and P. aeruginosa) by a series
of 1,4-dihydro-4-oxoquinoline (or 1,8-naphthyridine) 3-carboxylic
acids. Consistent biological data...
Cardiac A₁ adenosine receptors mediate cardioinhibitory
properties of adenosine and structural congeners. The objective of
these studies was to increase our understanding of molecular
processes involved in ligand interactions with receptors mediating
cardioinhibitory effects of adenosine and the interactions of these
receptors with guanine nucleotide binding regulatory proteins.
Porcine atrial...
Gastric retention time of single unit dosage forms in swine was found
to be much longer than in humans. It was concluded that swine are not a
good animal model to study GI transit time of nonerodable or slowly eroded
dosage forms. Noneradable and slowly eroded dosage forms used to...
Dissolution profiles of two commercial products (Motrine and Rufen®) were analyzed and compared at 8 pH levels, ranging from pH 2.0 to pH 8.0. It was demonstrated, as expected, that the rate and extent of ibuprofen dissolution dissolution was pH dependent. In vitro dissolution characteristics of the ibuprofen solid dispersion...
It has been standard practice in the United States to separate lipid emulsions from the other components of total parenteral nutrition due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent...
An in vitro labeling procedure was developed based
on optimal conditions of anticoagulant, stannous ion
concentration, incubation time, and incubation
temperature. This procedure was used to investigate the
effects of various agents on Tc-99m RBC labeling yields.
These agents were inorganic ions, therapeutic agents,
biochemicals, chelating agents, oxidizing agents, an...
Male Sprague Dawley rats received a single intraperitoneal dose
of BCNU in experiments designed to measure biochemical changes associated with the pulmonary toxicity described for this agent. Changes in
serum and lung lavage angiotensin converting enzyme (ACE) activity
were measured to detect changes in pulmonary endothelial cell integrity. Alpha-1-proteinase inhibitor...
The effectiveness of three methods designed to inform
patients about digoxin side effects was evaluated. Subjects
were randomly assigned to receive information about their
digoxin by one of three treatment methods: (1) verbal
consultation alone, (2) A.S.H.P. printed leaflet, or
(3) both verbal consultation and leaflet. Treatments were
administered by...
Rats were given single i.p. injections of BCNU to
investigate changes in hepatic cytochrome P-450 content and
specific activity in male rats. Microsomal P-450 levels
were unchanged from 6 hours to 7 days after BCNU treatment
but by day 21 they had decreased 45%. Ethylmorphine N-demethylase
activity (nm product x...
Lactobacilli have been used in the dairy and pharmaceutical industries because of their nutritious and/or
therapeutic effects. Lactobacillus acidophilus and
Lactobacillus bulqaricus were isolated from a commercially
available product and studied for their growth and colony
characteristics as described in Chapter I and Chapter II.
Survival of these lactobacilli in...