Pharmacy and Pharmaceutical Sciences Commons^™

Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden

Articles

Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Subconjunctivally Implantable Hydrogels With Degradable And Thermoresponsive Properties For Sustained Release Of Insulin To The Retina., Gauri P. Misra, Ravi S.J. Singh, Tomas S. Aleman, Samuel G. Jacobson, Thomas W. Gardner, Tao L. Lowe

College of Pharmacy Faculty Papers

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying …

Assembly Of Arenavirus Envelope Glycoprotein Gpc In Detergent-Soluble Membrane Microdomains, Sudhakar S. Agnihothram, Brooke Dancho, Kenneth W. Grant, Mark L. Grimes, Douglas S. Lyles, Jack H. Nunberg

Biomedical and Pharmaceutical Sciences Faculty Publications

The family Arenaviridae includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. Genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. In the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern. Arenaviruses are enveloped virions that assemble and bud from the plasma membrane. In this study, we have characterized the microdomain organization of the virus envelope glycoprotein (GPC) on the cell surface by using immunogold electron microscopy. We find that Junin virus (JUNV) GPC …

Airway Smooth Muscle As An Immunomodulatory Cell., Gautam Damera, Omar Tliba, Reynold A. Panettieri, Jr.

College of Pharmacy Faculty Papers

Although pivotal in regulating bronchomotor tone in asthma, airway smooth muscle (ASM) also modulates airway inflammation in asthma. ASM myocytes secrete or express a wide array of immunomodulatory mediators in response to extracellular stimuli, and in chronic severe asthma, increases in ASM mass may also render the airway irreversibly obstructed. Although the mechanisms by which ASM secretes cytokines and chemokines are shared with those regulating immune cells, there exist unique ASM signaling pathways that may provide novel therapeutic targets. This review provides an overview of our current understanding of the proliferative as well as synthetic properties of ASM.

Transcriptional Regulation Of Cytokine Function In Airway Smooth Muscle Cells., Deborah Clarke, Gautam Damera, Maria B. Sukkar, Omar Tliba

College of Pharmacy Faculty Papers

The immuno-modulatory properties of airway smooth muscle have become of increasing importance in our understanding of the mechanisms underlying chronic inflammation and structural remodeling of the airway wall in asthma and chronic obstructive pulmonary disease (COPD). ASM cells respond to many cytokines, growth factors and lipid mediators to produce a wide array of immuno-modulatory molecules which may in turn orchestrate and perpetuate the disease process in asthma and COPD. Despite numerous studies of the cellular effects of cytokines on cultured ASM, few have identified intracellular signaling pathways by which cytokines modulate or induce these cellular responses. In this review we …

Training Tomorrow’S Providers And Expanding Access To Peginterferon/Ribavirin Combination Therapyfor Chronic Hepatatis C In Underinsured/Uninsured Patients: Final Outcomes Of A Pilot, Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Suzanne J. Templer Do, Edward Norris Md, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Department of Medicine

No abstract provided.

Prediction Of Sublingual Bioavailability Of Buprenorphine In Newborns With Neonatal Abstinence Syndrome—A Case Study On Physiological And Developmental Changes Using Nonmem And Simcyp, Di Wu, Walter K. Kraft, Michelle E. Ehrlick, Jeffrey S. Barnett

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Poster presented at 2009 American College of Clinical Pharmacology conference in Orlando. April 24-28.

Background: About 55 to 94% of infants born to opioid dependent mothershave neonatal abstinence syndrome (NAS). Buprenorphine (BUP) is usedclinically as an analgesic and a detoxification agent and a maintenancetreatment for opioid dependence. No data, however, has been reported about the use of sublingual administration of BUP below the age of 4 year, especially for term infants with NAS.

Objectives: Characterize pharmacokinetics (PK) of BUP in newborn patients;Evaluate the developmental changes in newborns in order to assist dosingoptimization in ongoing clinical studies.

Methods: In silico prediction …

Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam E. Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias J. Schnell, Laurence C. Eisenlohr, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory …

The Proteolytic Stability And Cytotoxicity Studies Of L‐Aspartic Acid And L‐Diaminopropionic Acid Derived Β‐Peptides And A Mixed Α/Β‐Peptide, Sahar Ahmed, Kamaljit Kaur

Pharmacy Faculty Articles and Research

The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. β‐Peptides that contain an additional methylene group in the backbone, are gaining recognition from a pharmaceutical stand point as they are considerably more resilient to proteolysis and metabolism. Recently, we reported two new classes of β‐peptides, β³‐ and β²‐peptides derived from l‐aspartic acid and l‐diaminopropionic acid, respectively. Here, we report the proteolytic stability of these β‐peptidic compounds and a mixed α /β‐peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The …

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

Interactions Of Alkali Cations With Glutamate Transporters, David C. Holley, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

The transport of glutamate is coupled to the co-transport of three Na+ ions and the countertransport of one K+ ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure …

Urinary Levoglucosan As A Biomarker Of Wood Smoke Exposure: Observations In A Mouse Model And In Children, Christopher T. Migliaccio, M. A. Bergauff, Christopher P. Palmer, Forrest Jessop, Curtis W. Noonan, Tony Ward

Biomedical and Pharmaceutical Sciences Faculty Publications

BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. OBJECTIVES: In …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP in plasma, 375 -> 357 for …

A Glycosylated Recombinant Human Granulocyte Colony Stimulating Factor Produced In A Novel Protein Production System (Avi-014) In Healthy Subjects: A First-In Human, Single Dose, Controlled Study., Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, …

Targeting The Cgmp Pathway To Treat Colorectal Cancer, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This presentation was given in 2009 for the Seminar Series of the Department of Molecular Physiology and Biophysics, Thomas Jefferson University (Philadelphia, PA, USA). It illustrates the role of the calcium-sensing receptor (CaR) and matrix metalloproteinase 9 (MMP-9) as critical downstream mediators of the anticancer GCC pathway in intestine.

Questa presentazione e’ stata effettuata per il Seminar Series del Dipartimento di Fisiologia Molecolare e Biofisica dell’Universita’ del Thomas Jefferson (Filadelfia, USA). La presentazione illustra l’importante ruolo del CaR ed MMP-9 come mediatori della soppressione del processo tumorale dell’intestino da parte del recettore GCC.

Neurovirulence Of Polytropic Murine Retrovirus Is Influenced By Two Separate Regions On Opposite Sides Of The Envelope Protein Receptor Binding Domain, Karin E. Peterson, Susan Pourciau, Min Du, Rachel Lacasse, Melissa Pathmajeyan, David J. Poulsen, Mavis Agbandje-Mckenna, Kathy Wehrly, Bruce Chesebro

Biomedical and Pharmaceutical Sciences Faculty Publications

Changes in the envelope proteins of retroviruses can alter the ability of these viruses to infect the central nervous system (CNS) and induce neurological disease. In the present study, nine envelope residues were found to influence neurovirulence of the Friend murine polytropic retrovirus Fr98. When projected on a three-dimensional model, these residues were clustered in two spatially separated groups, one in variable region B of the receptor binding site and the other on the opposite side of the envelope. Further studies indicated a role for these residues in virus replication in the CNS, although the residues did not affect viral …

Design, Synthesis, And Evaluation Of Small Molecules In The Discovery Of Novel Antimicrobial Agents, Kimberly D. Grimes

Theses and Dissertations (ETD)

The increasing prevalence of antibiotic-resistant bacteria, including Mycobacterium tuberculosis, Streptococcus pneumoniae, Staphylococcus aureus, and Enterococcus faecalis, pushes us to discover new antibacterial agents to maintain adequate patient coverage. This body of work highlights the use of medicinal chemistry methodologies that encompass cross-disciplinary fields of study. Chapter 1 gives an introduction to the antibacterial drug targets, resistance, and how scientists are working to overcome obstacles encountered with drug-resistant bacteria. It also details modern medicinal chemistry applications in antimicrobial drug discovery. Chapter 2 details the use of a structure-guided library approach to drug design, in which large virtual libraries against the target …

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 10^10-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …

Composites Comprising Cholesterol And Carboxymethyl Cellulose, Vuk Uskoković

Pharmacy Faculty Articles and Research

Whereby cholesterol presents one of the major fatty substances in human body, carboxymethyl cellulose is a water-soluble derivative of cellulose, the most abundant dietary fiber. Whereas on one hand in vivo precipitation of cholesterol is the major cause of atherosclerosis, dietary fibers are on the other hand known for their ability to clean the fatty plaque deposited on intestinal pathways, and prevent its build-up in other critical areas within the organism. In this work, a method for the preparation of a composite material comprising cholesterol and carboxymethyl cellulose from 1-hexanol/water biphase mixtures is reported. Specificity of the interaction between the …

Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed

Pharmacy Faculty Articles and Research

β-Peptides made from L-aspartic acid monomers form a new class of β³-peptides. Here we report the first three-dimensional NMR solution structure of a β³-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β³-peptides formed from β³-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we …

Pdgf-Driven Proliferation, Migration, And Il8 Chemokine Secretion In Human Corneal Fibroblasts Involve Jak2-Stat3 Signaling Pathway, Neeraj Vij, Ajay Sharma, Mahesh Thakkar, Sunilima Sinha, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: Platelet-derived growth factor (PDGF) is associated with corneal fibroblast migration and proliferation and plays an important role in corneal wound healing. However, the intracellular mechanisms of PDGF-mediated functions in corneal fibroblasts are poorly understood. We tested the hypothesis that PDGF functional activities in the cornea involve the Janus kinase-2/signal transducers and activators of transcription-3 (JAK2-STAT3) signaling pathway and whether PDGF induces the expression of suppressors of cytokine signaling 3 (SOCS3), belonging to the novel family of feedback regulators of cytokine and growth factor activities.

Methods: Human corneal fibroblast (HSF) cultures were used as an in vitro model for functional …

Tumor Epithelial Cell Matrix Metalloproteinase 9 (Mmp-9) Is A Prognostic Marker In Colorectal Cancer, Ds Zuzga, Av Gibbons, P Li, Wj Lubbe, I Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at American Association Cancer Research in 2008

Zuzga D.S., Gibbons A.V., Li P., Lubbe W.J., Chervoneva I., Pitari G.M. “Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer”. In: American Association for Cancer Research Special Conference, Molecular Diagnostics in Cancer Therapeutic Development: Proceedings; 2008 Sept 22-25; Philadelphia, PA. Abstract A40.

Colorectal cancer is the second leading cause of cancer-related mortality indeveloped nations. Mortality from colon cancer largely reflects metastasis, thespread of the disease to distant sites. Early diagnosis of pre-metastatic diseaseand accurate stratification of patients with metastasis is pivotal to decreasemortality rates from colon cancer by effectively …

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …

The Mechanism Of Silver Dissolution For Biomedical Devices And Hygienic Coating Applications., Yanmei Ma

Doctoral

This work focuses on the mechanism of silver dissolution for biomedical and hygienic coating applications. The research work began from the investigation of silver dissolution behaviour from pure silver and silver-platinum alloys in solutions with or without chloride using the technique of cyclic volammetry (CV). A zero resistance amperometry (ZRA) measurement was carried out to study the effect of platinum on the silver dissolution behaviour in 0.89%wt. NaCI solution. The mechanism of silver dissolution from pure silver and silver-platinum alloys in 0.89%wt. NaCI solution was proposed by an equivalent circuit model under the investigation of electrochemical impedance spectroscopy (EIS). It …

Role Of Medial Prefrontal Cortical Group Ii Metabotropic Glutamate Receptor In The Development Of Cocaine Sensitization, Xiaohu Xie

Theses and Dissertations (ETD)

The current studies examined the role of medial prefrontal cortical (mPFC) group II metabotropic glutamate receptors (mGluR_2/3) in the development of cocaine sensitization. Initial studies demonstrated that intra-mPFC injection of the mGluR_2/3 receptor agonist, APDC, dose-dependently reduced acute behavioral response to cocaine (0.015-15 nmol/side with significant effects starting at 1.5nmol/side). The effects of APDC were prevented by intra-mPFC co-injections of an mGluR_2/3 antagonist, LY341495 (1.5 nmol/side). Repeated intra-mPFC APDC (1.5 nmol/side) injections also prevented the initiation of behavioral and neurochemical sensitization, which is defined as enhanced nucleus accumbens (NAc) dopamine response to cocaine. Once sensitization was …

The Pharmacokinetics Of Taurolidine Metabolites In Healthy Volunteers., Li Gong, Howard E Greenberg, James L Perhach, Scott A Waldman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the …

Effect Of Standard Treatment Guidelines With Or Without Prescription Audit On Prescribing For Acute Respiratory Tract Infection (Ari) And Diarrhoea In Some Thana Health Complexes (Thcs) Of Bangladesh, M. O. Faruk Khan, A.K. Azad Chowdhury, M. A. Matin, K. Begum, M. A. Galib

Pharmaceutical Science and Research

Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh. A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in randomly selected 60 thana health complexes (THCs) of Dhaka division of Bangladesh. In the 38 of 60 THCs, the prescribers did not comply with the standard treatment guidelines (STG) for ARI. They are marked as 'unsatisfactory performers'. In these THCs unnecessary antibiotics were prescribed in more than 50% of the encounters. The study further revealed that in 26 THCs, comprising 41.6% of the 38 THCs, the situation was even worse …