Drugs and therapeutics

Doxycycline is one of the most commonly used antibiotics in clinical medicine. Its broad spectrum of activity along with tolerable adverse effects makes it more palatable and compliant to patients. Improved understanding of mechanisms of actions of doxycycline has provided additional potential novel uses in clinical medicine apart from just...

Breakthrough pain (BTP) management is an unmet clinical need. BTP is poorly diagnosed, rarely evaluated and inadequately reated. BTP is transitory exacerbation of pain experienced by the patient who has relatively stable and adequately controlled baseline pain. BTP is reported to be common in adults and children with cancer as...

Inhaled corticosteroids are the mainstay of asthma therapy, but there is now compelling evidence that addition of a long-acting inhaled β2-agonist, such as formoterol, gives better control in terms of reduced symptoms, improved lung function and reduced exacerbations in patients with mild to severe persistent asthma than increasing the dose...

The histone tails of histone octamers play an intricate role in transcription, and aid the histone interaction and binding with the negatively charged DNA phosphate backbone. Histone acetyl transferases and histone deacetylase inhibitors respectively accomplish acetylation and deacetylation of the lysine residue of the histone tail. Vorinostat is the first...

In these studies, we tested the effectiveness of combinatorial gene delivery to CCR5-expressing cell lines and primary cells to enhance resistance to HIV-1 infection. The transgenes used were chosen both to decrease membrane CCR5 and to inhibit HIV-1 replication, and were delivered using Tag-deleted SV40-derived vectors. rSV40s are very effective...

Aldosterone blockade has been shown to be effective in reducing total mortality in patients with severe heart failure due to systolic left ventricular dysfunction and in patients with heart failure post myocardial infarction. Increasing evidence suggests that aldosterone blockade alone and or in conjunction with an angiotensin converting enzyme inhibitor...

Objectives: Review and summarize the mechanism of action of methylnaltrexone bromide (methylnaltrexone) and its effectiveness in the treatment of opioid-induced constipation. Data Source: A multi-database search was conducted using PubMed and MEDLINE databases, in addition to electronic links to related articles and references. Background: Opioids are effective medications for the management of...

Oritavancin is a semisynthetic lipoglycopeptide with in vitro activity against a variety of aerobic Gram-positive pathogens (including drug-resistant forms of staphylococci, streptococci, and enterococci) and select anaerobic organisms. Available published clinical efficacy and safety studies in humans to date focus primarily in the treatment of complicated skin and skin structure...

Narcolepsy is a complex disease with multiple symptoms that include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Pharmacologic management of patients with narcolepsy is based on treating these symptoms. Sodium oxybate, a neurotransmitter product of γ-amino butyric acid (GABA), is a Schedule III controlled substance in the US,...

Lennox-Gastaut syndrome is an epileptic encephalopathy starting in early childhood consisting of the triad of cognitive impairment, multiple seizures types and slow spike-wave complexes in the electroencephalogram. Global developmental delay is usually evident before the onset in patients with symptomatic LGS whereas children with cryptogenic LGS might have a normal...

NQO1 (NAD(P)H:quinoneoxidoreductase 1) is a reductive enzyme that is an important activator of bioreductive antitumor agents. NQO1 activity varies in individual tumors but is generally higher in tumor cells than in normal cells. NQO1 has been used as a target for tumor specific drug development. We investigated a series of...

A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing...

The metabolism of arachidonic acid by either the cyclooxygenase (COX) or lipoxygenase (LOX) pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer. It is now considered that they play important roles in tumor promotion, progression, and metastasis, also, the involvement of...

Shark liver oil (SLO), is used in natural medicine as immunity stimulant, cardiovascular protector and anti ageing reagent. These properties were related with the high amounts of alkylglycerols (22%) obtained from Greenland shark liver. After a control of the mean SLO composition by NMR and MS, surface and membrane interactions...

Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD) was the incentive of this pilot study. Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease) with disease activity grade 2–10 on simple colitis...

Memantine protects cultured neurons from excitotoxin-induced cell-death; it attenuated loss of cholinergic neurons in the CNS induced by injection of NMDA into the basal forebrain of rats. It has been shown that memantine induced production of brain-derived neurotrophic factor (BDNF), a substance shown to promote survival and differentiation of CNS...

Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic...

Background: AlphaIIb/beta3 (αIIb/β3) complex is an important integrin that is involved in the final step of platelet aggregation. Peptides derived from either αIIb or β3 have demonstrated to have an effect on the activation of the complex and its ability to bind fibrinogen. We have previously defined a peptide from...

Cholesterol is transported around the body in the form of lipoprotein (lipid/protein) complexes, because it is almost insoluble in water. High-density lipoprotein (HDL) particles transport cholesterol from tissues back to the liver for excretion. Epidemiological studies have shown an inverse relationship between blood levels of HDL-cholesterol (HDL-c) and the incidence...

The rapidly expanding data sets derived from genomic and transcriptomic analyses have allowed greater understanding of structural and functional network patterns within the genome resulting in a realignment of thinking within a systems biologic framework of cancer. However, insofar as spatially and temporally dynamic differential gene expression at the protein...

This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the...

Chaperone therapy is a newly developed molecular approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. We found two valienamine derivatives, N-octyl-4-epi-β-valienamine (NOEV) and N-octyl-β-valienamine (NOV), as promising therapeutic agents for human β-galactosidase deficiency disorders (mainly GM1-gangliosidosis) and β-glucosidase deficiency disorders (Gaucher disease), respectively. We...

RNA is increasingly recognized for its significant functions in biological systems and has recently become an important molecular target for therapeutics development. Aminoglycosides, a large class of clinically significant antibiotics, exert their biological functions by binding to prokaryotic ribosomal RNA (rRNA) and interfering with protein translation, resulting in bacterial cell...

Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been...

Integrins have been reported to mediate cell survival, proliferation, differentiation, and migration programs. For this reason, the past few years have seen an increased interest in the implications of integrin receptors in cancer biology and tumor cell aggression. This review considers the potential role of integrins in cancer and also...

The heterogeneity of symptoms and disease progression observed in synucleinopathies, of which Parkinson’s disease (PD) is the most common representative, poses large problems for the discovery of novel therapeutics. The molecular basis for pathology is currently unclear, both in familial and in sporadic cases. While the therapeutic effects of L-DOPA...

Cancer is one of the leading causes of deaths in the Western world. Approximately one-third of these deaths are preventable by lifestyle factors, including modification of nutritional habits. Studies have demonstrated that adequate nutrition with certain types of foods containing bioactive compounds might offer significant protection against carcinogenesis. Soybeans contain...

Tacrolimus (FK506), which was isolated from the fermentation broth of Streptomyces tsukubaensis No. 9993, has an immunosuppressive effect. In T-lymphocytes, FK506 binds to the intracellular receptor, a 12-kDa FK506-binding protein (FKBP12). The FK506-FKBP12 complex binds to the phosphatase calcineurin (CN) and inhibits the activity of CN. By inhibition of the...

The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer’s and Parkinson’s disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding...

The myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. The genetic and epigenetic pathways that determine disease stage and progression are largely unknown. In the current study we used gene expression microarray methodology to examine the gene expression differences between normal hematopoietic cells and...

In the review, the nature of protein multifunctionality is analyzed. In the first part of the review the principles of structural/functional organization of protein are discussed. In the second part, the main mechanisms involved in development of multiple functions on a single gene product(s) are analyzed. The last part represents...

Sirtuins are NAD+-dependent histone deacetylases (Class III HDACs). Recently, Sirtuins have been shown to play important roles, both direct and indirect, in transcriptional regulation. This transcriptional control, through incorporation of Sirtuins into transcription complexes and deacetylation of histones locally at gene promoters, or direct interaction with specific transcription factors, is...

In the last two decades there has been considerable progress in our understanding of the role of sphingolipids in controlling signal transduction processes, particularly in the mechanisms leading to regulation of cell growth and death. Ceramide is a well-characterized sphingolipid metabolite and second messenger that can be produced by cancer...

Gene associated with retinoid-interferon-β-induced mortality (GRIM)—19, was originally identifi ed as a critical regulatory protein necessary for Interferon-β-Retinoic acid-induced cell death. Overexpression of GRIM-19 activates cell death and its suppression or inactivation promotes cell growth. GRIM-19 targets multiple proteins/pathways for exerting growth control and cell death. However, GRIM-19 is also...

A great amount of literature has demonstrated a connection between obesity, visceral fat and the metabolic disorders such as hyperglycemia, hypertension, and hyperlipidemia. Lately, there has been an increased interest in understanding if cancer is related to obesity and visceral fat accumulation. The prevalence of both obesity and cancer are...

Sudeep K. Bose, Rebecca S. Bullard and Carlton D. Donald Department of Pathology and Laboratory Medicine, Medical University of South Carolina (MUSC), 165 Ashley Avenue, PO Box 250620, Charleston, SC—29425, U.S.A. Abstract Prostate cancer is the second leading cause of cancer death among men in the United States...

Viggo Jønsson1, Geir E. Tjønnfjord2, Tom B. Johannesen3, Sven Ove Samuelsen4 and Bernt Ly5 1Department of Hematology, Aker University Hospital, University of Oslo, Norway. 2Department of Hematology, Rikshospital and Radium Hospital, University of Oslo, Norway. 3,5The National Norwegian Cancer Registry, Oslo, Norway. 4Department of Biostatistics, Faculty of Mathematics, University...

Sheng Wang and Douglas V. Faller Boston University School of Medicine, Cancer Research Center, Boston, MA, U.S.A. Abstract Tumor formation results from alterations in the normal control of cell proliferation. In the past decade, much attention in cancer research has been focused on the function of proto-oncogenes...

Tobias Gremmel1, Susanne Wild1, Winfried Schuller2, Viola Kürten3, Klaus Dietz4, Jean Krutmann1 and Mark Berneburg2 1Institut für Umweltmedizinische Forschung at the Heinrich-Heine-University gGmbH, Auf´m Hennekamp 50, D-40225 Düsseldorf, Germany.2 Molecular Oncology and Aging, Department of Dermatology, Eberhard-Karls-University, Tübingen, Germany.3 Department of Dermatology, Heinrich-Heine-University, Moorenstr. 5, D-40225 Düsseldorf, Germany.4 Department...