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Methods and Findings in Experimental... May 2007Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from...
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, 101M, AAV-AADC, AGN-201904-Z; Agomelatine, AN-0128, AN-2690, Arginine butyrate, Asenapine maleate; Belinostat, Bortezomib, BQ-123, BQ-788; Bucindolol hydrochloride; Certolizumab pegol; Dasatinib, Denosumab, Desvenlafaxine succinate; Ecogramostim, Esomeprazole magnesium; Homoharringtonine; huN901-DM1, Hyaluronic acid; Incyclinide; L-Arginine hydrochloride; Mepolizumab; Nematode anticoagulant protein c2, Nilotinib; Oblimersen sodium; R-115866, Raltegravir potassium, Retapamulin, Romidepsin, Rusalatide acetate; Sarcosine, SCIO-469, Soblidotin, Sorivudine; Tilarginine hydrochloride, Tipifarnib; Uracil; Vildagliptin.
Topics: Clinical Trials as Topic; Humans
PubMed: 17609744
DOI: No ID Found -
Comptes Rendus Des Seances de... Jul 1981
Topics: Animals; Arginine; Butyrates; Dose-Response Relationship, Drug; Encephalomyocarditis virus; Enterovirus Infections; Lysine; Mice; Structure-Activity Relationship
PubMed: 6272953
DOI: No ID Found -
The Laryngoscope Apr 2002Head and neck squamous cell carcinoma (HNSCC) is a major cause of mortality. Despite advances in therapeutic modalities, recurrences and second primaries are commonly...
OBJECTIVES/HYPOTHESIS
Head and neck squamous cell carcinoma (HNSCC) is a major cause of mortality. Despite advances in therapeutic modalities, recurrences and second primaries are commonly observed. Biological agents that can suppress growth of tumors that are otherwise difficult to treat are greatly needed. The present study examined the effects of short-chain fatty acids on HNSCC cell lines.
STUDY DESIGN
The effects of short-chain fatty acids on HNSCC cells was examined using tissue culture and immunoblotting techniques.
METHODS
The effects of four short-chain fatty acids, arginine butyrate, alpha-methyl hydrocinnamic acid, 2,2-dimethylbutyrate, and alpha-lipoic acid, were evaluated on four HNSCC cell lines (FaDu, SCC9, SCC25, and Detroit-562). Proliferation assays were performed by means of spectrophotometric techniques. Histone deacetylase activity was assessed by identifying the amount of acetylated histone H4. Involucrin expression was determined to assess cellular differentiation.
RESULTS
Inhibition of cellular proliferation was determined after 5 days of incubation with increasing doses with short-chain fatty acids. Arginine butyrate and alpha-lipoic acid were most effective in suppressing growth. Arginine butyrate demonstrated strong histone deacetylase inhibition in FaDu cells, while not inducing cellular differentiation. The short-chain fatty acid alpha-lipoic acid demonstrated weak histone deacetylase inhibition but was the only short-chain fatty acid that induced involucrin expression in at least two of the cell lines. Histone deacetylase inhibitory activity or induction of involucrin expression correlated with suppression of cell growth.
CONCLUSIONS
Short-chain fatty acids have variable effects on HNSCC cells. Arginine butyrate and alpha-lipoic acid are the most effective in suppressing growth and appear to do so through different biochemical mechanisms. These compounds warrant further research as chemotherapeutic or chemopreventive agents in HNSCC.
Topics: Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Line; Fatty Acids, Volatile; Head and Neck Neoplasms; Histone Deacetylase Inhibitors; Humans; Tumor Cells, Cultured
PubMed: 12150517
DOI: 10.1097/00005537-200204000-00010 -
International Journal of... Nov 1995The effects of the complexes of inosine (Ino) analogues of isoprinosine on the immune response to sheep red blood cells (SRBC), in plaque-forming cells assay (PFC), in... (Comparative Study)
Comparative Study
The effects of the complexes of inosine (Ino) analogues of isoprinosine on the immune response to sheep red blood cells (SRBC), in plaque-forming cells assay (PFC), in mice spleen, and on the Fc-dependent SRBC phagocytosis in mice peritoneal macrophages were investigated. Molar ratios of 1:3 of the complexes of inosine with N,N-dimethylaminopropanol-2-p-acetaminobenzoate (isoprinosine), and 8-thioinosine with N,N-dimethylaminopropanol-2-p-acetaminobenzoate (OSI-177), inosine with L-arginine butyrate (OSI-2655), and 8-thioinosine with L-arginine butyrate (OSI-3648) were administered. The administered doses were 0.5, 5 and 50 mg/kg body weight. The compound OSI-2655 exceeded isoprinosine in PFC stimulation and phagocytosis activation. The compound OSI-3648 exceeded isoprinosine only in PFC stimulation in the case of immunization with a suboptimal SRBC dose. OSI-3648 stimulated the immune response in PRC better than isoprinosine, OSI-177, or OSI-2655, and maintained the ability to stimulate capture, but lost the ability to stimulate destruction processes of captured SRBC. L-Arginine butyrate in the doses equivalent to its content in the complexes did not affect the number of PFC. L-Arginine butyrate was able to stimulate the processes of destruction but its stimulation degree was inferior to the compound OSI-2655.
Topics: Adjuvants, Immunologic; Adrenergic beta-Agonists; Animals; Arginine; Butyrates; Erythrocytes; Female; Hemolytic Plaque Technique; Immunoglobulin Fc Fragments; Inosine; Isoproterenol; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Phagocytosis; Rats; Sheep
PubMed: 8788123
DOI: 10.1016/0192-0561(95)00084-4 -
Human Molecular Genetics May 2012Dystrophin, the protein responsible for X-linked Duchenne muscular dystrophy (DMD), is normally expressed in both muscle and brain, which explains that its loss also...
Dystrophin, the protein responsible for X-linked Duchenne muscular dystrophy (DMD), is normally expressed in both muscle and brain, which explains that its loss also leads to cognitive deficits. The utrophin protein, an autosomal homolog, is a natural candidate for dystrophin replacement in patients. Pharmacological upregulation of endogenous utrophin improves muscle physiology in dystrophin-deficient mdx mice, and represents a potential therapeutic tool that has the advantage of allowing delivery to various organs following peripheral injections. Whether this could alleviate cognitive deficits, however, has not been explored. Here, we first investigated basal expression of all utrophins and dystrophins in the brain of mdx mice and found no evidence for spontaneous compensation by utrophins. Then, we show that systemic chronic, spaced injections of arginine butyrate (AB) alleviate muscle alterations and upregulate utrophin expression in the adult brain of mdx mice. AB selectively upregulated brain utrophin Up395, while reducing expression of Up113 and Up71. This, however, was not associated with a significant improvement of behavioral functions typically affected in mdx mice, which include exploration, emotional reactivity, spatial and fear memories. We suggest that AB did not overcome behavioral and cognitive dysfunctions because the regional and cellular expression of utrophins did not coincide with dystrophin expression in untreated mice, nor did it in AB-treated mice. While treatments based on the modulation of utrophin may alleviate DMD phenotypes in certain organs and tissues that coexpress dystrophins and utrophins in the same cells, improvement of cognitive functions would likely require acting on specific dystrophin-dependent mechanisms.
Topics: Animals; Arginine; Brain; Butyrates; Dystrophin; Mice; Mice, Inbred mdx; Mice, Knockout; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; RNA, Messenger; Up-Regulation; Utrophin
PubMed: 22343141
DOI: 10.1093/hmg/dds047 -
Indian Pediatrics Mar 1994
Topics: Administration, Oral; Arginine; Butyrates; Chelating Agents; Chelation Therapy; Genetic Therapy; Humans; India; beta-Thalassemia
PubMed: 7896360
DOI: No ID Found -
Medical Oncology and Tumor... 1984The analysis of the likely physiological role of interferon during pregnancy and antitumor protection can be employed in developing a new strategy in antitumor therapy....
The analysis of the likely physiological role of interferon during pregnancy and antitumor protection can be employed in developing a new strategy in antitumor therapy. Indeed, pretreatment of the patients with a potent immune stimulation compensates to some extent interferon's immune repressive effects. Through the modulation of the cytoskeleton, interferon enhances macrophage activity. Moreover, butyrate by its own effect on the malignant phenotype increases interferon sensitivity in a number of malignant cells. All of these substances should be used at the lowest possible concentration delivered as closely as possible to the target area.
Topics: Amniotic Fluid; Animals; Arginine; Butyrates; Cytoskeleton; Extracellular Matrix; Female; Humans; Immune System; Interferons; Mice; Mice, Inbred AKR; Neoplasms; Pregnancy; Propionibacterium acnes; Rats; Sarcoma 180
PubMed: 6085812
DOI: 10.1007/BF02934981 -
The Journal of Laboratory and Clinical... Dec 1998The exposure of endothelial cells to hypoxic environments regulates the expression of a number of genes with products that are vasoactive or mitogenic for vascular...
The exposure of endothelial cells to hypoxic environments regulates the expression of a number of genes with products that are vasoactive or mitogenic for vascular tissue, including platelet-derived growth factor, endothelin-1, and endothelial nitric oxide synthase. Hypoxia is also known to alter the adhesive properties of endothelium toward a variety of blood cell types. Thrombospondin-1 (TSP-1) is a glycoprotein with major roles in cellular adhesion and vascular smooth muscle proliferation and migration. We report here that hypoxia induces TSP-1 gene and protein expression. Oxygen tensions of < or =30 torr resulted in TSP-1 transcript induction initially apparent at 1 to 6 hours, with maximal induction (6.5-fold+/-1.2-fold) within 24 to 48 hours in both human and bovine endothelial cells. TSP-1 protein levels remain elevated after 72 hours of continuous hypoxic exposure. The induction of TSP-1 steady-state transcript levels is caused in large part, if not entirely, by post-transcriptional stabilization of the TSP-1 mRNA. The TSP-1 induction by hypoxia is a graded and reversible physiologic response and can be mimicked by the use of cobalt chloride or the inhibition of nitric oxide production, suggesting both the involvement of a heme-containing oxygen sensor and a role for the endogenous production of nitric oxide in TSP-1 regulation. The effects of hypoxia both on the stabilization of the TSP-1 transcript and the stimulation of TSP-1 protein production are completely inhibited by arginine butyrate.
Topics: Animals; Arginine; Butyrates; Cattle; Cells, Cultured; Cobalt; Cycloheximide; Dactinomycin; Endothelium, Vascular; Gene Expression Regulation; Humans; Hydroxamic Acids; Hypoxia; NG-Nitroarginine Methyl Ester; Oxygen; RNA, Messenger; Thrombospondin 1
PubMed: 9851743
DOI: 10.1016/s0022-2143(98)90131-7 -
Journal of the American College of... Sep 1998The purpose of this study was to determine cost of care for leg ulcers in sickle cell patients and suggest an improved modality in ulcer care.
BACKGROUND
The purpose of this study was to determine cost of care for leg ulcers in sickle cell patients and suggest an improved modality in ulcer care.
STUDY DESIGN
We performed a retrospective study of a group of sickle cell disease patients with leg ulcers.
RESULTS
Eighteen patients with a leg ulcer (duration: mean, 53.7 months), sickle cell disease, and a mean of 20.7 years of age had various modalities of treatment with the only consistency in healing being a commercial moist-wound dressing.
CONCLUSIONS
There is no consistency in the treatment of the sickle cell patient with a leg ulcer. Treatment with a moist dressing had the best results.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Arginine; Bandages, Hydrocolloid; Butyrates; Colloids; Combined Modality Therapy; Cost-Benefit Analysis; Erythropoietin; Female; Hospital Costs; Humans; Leg Ulcer; Length of Stay; Male; Occlusive Dressings; Recombinant Proteins; Recurrence; Retrospective Studies; Wound Healing
PubMed: 9740188
DOI: 10.1016/s1072-7515(98)00196-3 -
Journal of Clinical Pharmacology Aug 2011Pharmacologic induction of fetal globin synthesis is an accepted therapeutic strategy for treatment of the beta hemoglobinopathies and thalassemias, as even small... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of safety and pharmacokinetics of sodium 2,2 dimethylbutyrate, a novel short chain fatty acid derivative, in a phase 1, double-blind, placebo-controlled, single-dose, and repeat-dose studies in healthy volunteers.
Pharmacologic induction of fetal globin synthesis is an accepted therapeutic strategy for treatment of the beta hemoglobinopathies and thalassemias, as even small increases in hemoglobin F (HbF) levels reduce clinical severity in sickle cell disease (SCD) and reduce anemia in beta thalassemia. Prior generation short chain fatty acid therapeutics, arginine butyrate (AB), and phenylbutyrate, increased fetal and total hemoglobin levels in patients, but were limited by high doses or intravenous (IV) infusion. A fetal globin-inducing therapeutic with convenient oral dosing would be an advance for these classic molecular diseases. Healthy adult human subjects were treated with a novel short chain fatty acids (SCFA) derivative, sodium 2,2 dimethylbutyrate (SDMB), or placebo, with 1 of 4 single dose levels (2, 5, 10, and 20 mg/kg) or daily doses (5, 10, or 15 mg/kg) over 14 days, and monitored for adverse clinical and laboratory events, drug levels, reticulocytes, and HbF assays. SDMB was well-tolerated with no clinically significant adverse events related to study medication. The terminal half-life ranged from 9 to 15 hours. Increases in mean absolute reticulocytes were observed at all dose levels in the 14-day study. The favorable pharmacokinetics (PK) profiles and safety findings indicate that SDMB warrants further investigation for treatment of anemic subjects with beta hemoglobinopathies.
Topics: Administration, Oral; Adolescent; Adult; Biological Availability; Blood Cell Count; Butyrates; Dose-Response Relationship, Drug; Double-Blind Method; Drugs, Investigational; Female; Fetal Hemoglobin; Food-Drug Interactions; Half-Life; Hematinics; Humans; Male; Metabolic Clearance Rate; Plasma; Reticulocytes; Urine; Young Adult
PubMed: 21422239
DOI: 10.1177/0091270010379810