ABSTRACT
Synbiotics, a combination of prebiotics and probiotics, produce synergistic effects to promote gastrointestinal health. Herein, we investigated the synbiotic interaction between the Lactobacillus rhamnosus strain GG (LGG; a probiotic strain) and tagatose (a prebiotic) in a dextran sulfate sodium (DSS)-induced colitis murine model. Initially, body weight, food intake, and clinical features were dramatically decreased after treatment with DSS, and the addition of LGG, tagatose, or both ameliorated these effects. In our pyrosequencing analysis of fecal microbiota, DSS treatment increased the abundance of Proteobacteria and decreased that of Firmicutes. When LGG and tagatose were administered as synbiotics, the gut microbiota composition recovered from the dysbiosis caused by DSS treatment. In particular, the abundance of Bacteroides, Lactobacillus, and Akkermansia was significantly associated with probiotic, prebiotic, and synbiotic treatments. Taken together, our results suggest that LGG and tagatose as synbiotics can alleviate colitis, and synbiotics could be applied as dietary supplements in dairy foods such as yogurt and cheese.
Subject(s)
Colitis/chemically induced , Colitis/therapy , Hexoses/therapeutic use , Lacticaseibacillus rhamnosus , Synbiotics , Animals , Dextran Sulfate/toxicity , Feces/microbiology , Hexoses/administration & dosage , Iron Chelating Agents/administration & dosage , Iron Chelating Agents/pharmacology , Lactobacillus , Lacticaseibacillus rhamnosus/classification , Mice , MicrobiotaABSTRACT
CONTEXT: Gout is a painful disorder which does not have an efficient delivery system for its treatment. OBJECTIVE: Development and in vitro, in vivo evaluation of allopurinol-loaded nonionic surfactant-based niosomes was envisaged. MATERIALS AND METHODS: Niosomes were prepared with Span 20 and Tween 20 (1:1 molar ratio) using ether injection method. The formulations were screened for entrapment efficiency, particle size analysis, zeta potential, release kinetics, in vivo activity, and stability studies. RESULT: Stable, spherical vesicles of average particle size 304 nm with zeta-potential and entrapment efficiency of 22.2 mV and 79.44 ± 0.02%, respectively, were produced. In vitro release study revealed 82.16 ± 0.04% release of allopurinol within 24 h. The niosomal formulation was further evaluated for its antigout potential in monosodium urate (MSU) crystal induced gout animal model. The formulation demonstrated significant uric acid level reduction and enhanced antigout activity when compared with the pure allopurinol. DISCUSSION: The better antigout activity displayed by niosomal formulation could be attributed to sustained release of drug, higher drug solubility within biological fluids, better membrane interaction, smaller size, and presence of cholesterol and surfactant. CONCLUSIONS: This study reveals that niosomes can be an efficient delivery system for the treatment of gout.
Subject(s)
Allopurinol/therapeutic use , Disease Models, Animal , Drug Delivery Systems , Gout/drug therapy , Administration, Oral , Allopurinol/administration & dosage , Allopurinol/chemistry , Animals , Gout/chemically induced , Gout/pathology , Hexoses/administration & dosage , Hexoses/chemistry , Hexoses/therapeutic use , Liposomes/administration & dosage , Liposomes/chemistry , Liposomes/therapeutic use , Particle Size , Polysorbates/administration & dosage , Polysorbates/chemistry , Polysorbates/therapeutic use , Rabbits , Surface Properties , Uric AcidABSTRACT
Nanoemulsions are feasible delivery systems of lipophilic compounds, showing potential as edible coatings with enhanced functional properties. The aim of this work was to study the effect of emulsifier type (stearic acid (SA), Tween 80 (T80) or Tween 80/Span 60 (T80/S60)) and emulsification process (homogenization, ultrasound or microfluidization) on nanoemulsion formation based on oxidized corn starch, beeswax (BW) and natural antimicrobials (lauric arginate and natamycin). The response variables were physicochemical properties, rheological behavior, wettability and antimicrobial activity of BW-starch nanoemulsions (BW-SN). The BW-SN emulsified using T80 and microfluidized showed the lowest droplet size (77.6 ± 6.2 nm), a polydispersion index of 0.4 ± 0.0 and whiteness index (WI) of 31.8 ± 0.8. This BW-SN exhibited a more negative ζ-potential: -36 ± 4 mV, and Newtonian flow behavior, indicating great stability. BW-SN antimicrobial activity was not affected by microfluidization nor the presence of T80, showing inhibition of the deteriorative fungi R. stolonifer, C. gloeosporioides and B. cinerea, and the pathogenic bacterium S. Saintpaul. In addition, regardless of emulsifier type and emulsification process, BW-SN applied on the tomato surface exhibited low contact angles (38.5° to 48.6°), resulting in efficient wettability (-7.0 mN/m to -8.9 mN/m). These nanoemulsions may be useful to produce edible coatings to preserve fresh-produce quality and safety.
Subject(s)
Anti-Infective Agents/therapeutic use , Drug Delivery Systems , Nanocomposites/chemistry , Waxes/chemistry , Anti-Infective Agents/chemistry , Emulsions/chemistry , Emulsions/therapeutic use , Hexoses/chemistry , Hexoses/therapeutic use , Humans , Nanocomposites/therapeutic use , Polysorbates/chemistry , Polysorbates/therapeutic use , Starch/chemistry , Starch/therapeutic use , Stearic Acids/chemistry , Stearic Acids/therapeutic useABSTRACT
OBJECTIVES: Catheter-related bloodstream infections (CRBSIs) are common healthcare-associated infections associated with increased morbidity and medical costs. Antiseptic- and antibiotic-coated central venous catheters (CVCs) have been proposed to reduce the incidence of CRBSIs, with variable success. The aim of this study was to determine the in vivo antibiofilm activity of biocompatible and inexpensive compounds, such as cerium nitrate, chitosan and hamamelitannin, against usual agents of CRBSIs. METHODS: The antibiofilm effect of cerium nitrate, chitosan and hamamelitannin was tested against Staphylococcus epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans in a mouse foreign body infection model, using polyurethane catheter segments. Biofilm formation was assessed with a crystal violet assay to quantify the total biomass, with a tetrazolium reduction assay to quantify the metabolic activity and with scanning electron microscopy. RESULTS: At subinhibitory concentrations, cerium nitrate significantly reduced biofilm formation by C. albicans, chitosan significantly decreased biofilm formation by S. epidermidis and C. albicans, and hamamelitannin significantly inhibited all bacterial biofilms. DISCUSSION: The in vivo antibiofilm effect of cerium nitrate against C. albicans and of chitosan against C. albicans and S. epidermidis, at subinhibitory concentrations, makes them promising alternatives to coat CVCs. Moreover, the microbicidal effect on a wider range of CVC colonizers was previously reported in vitro for both compounds, at higher concentrations. For all bacterial strains, the highest in vivo antibiofilm efficacy was achieved with hamamelitannin. For A. baumannii, this is the first report of in vivo inhibition.
Subject(s)
Anti-Infective Agents/pharmacology , Biofilms/drug effects , Catheter-Related Infections/drug therapy , Cerium/pharmacology , Chitosan/pharmacology , Gallic Acid/analogs & derivatives , Hexoses/pharmacology , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Animals , Anti-Infective Agents/therapeutic use , Biofilms/growth & development , Candida albicans/drug effects , Candida albicans/growth & development , Candidiasis/drug therapy , Candidiasis/microbiology , Catheter-Related Infections/microbiology , Cerium/therapeutic use , Chitosan/therapeutic use , Female , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , Hexoses/therapeutic use , Mice , Mice, Inbred BALB C , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/growth & developmentABSTRACT
Nearly 285 million people worldwide, with 10% being Americans, suffer from diabetes mellitus and its associated comorbidities. This is projected to increase by 6.5% per year, with 439 million inflicted by year 2030. Both morbidity and mortality from diabetes stem from the consequences of microvascular and macrovascular complications. Of the 285 million with diabetes, over a quarter of a million die per year from related complications, making diabetes the fifth leading cause of death in high-income countries. These startling statistics illustrate the therapeutic failure of current diabetes drugs to retard the progression of diabetes. These statistics further illustrate the continual need for further research and development of alternative drugs with novel mechanisms to slow disease progression and disease complications. The treatment algorithm updated in 2008 by American Diabetes Association and the European Association for the Study of Diabetes currently recommends the traditional medications of metformin, either as monotherapy or in combination with sulfonylurea or insulin, as the preferred choice in the tier 1 option. The algorithm only suggests addition of alternative medications such as pioglitazone and incretin-based drugs as second-line agents in the tier 2 "less well-validated" option. However, these traditional medications have not proven to delay the progressive course of diabetes as evidence of increasing need over time for multiple drug therapy to maintain sufficient glycemic control. Because current diabetes medications have limited efficacy and untoward side effects, the development of diabetes mellitus drugs with newer mechanisms of action continues. This article will review the clinical data on the newly available incretin-based drugs on the market, including glucagon-like peptide agonists and of dipeptidyl peptidase type-4 inhibitors. It will also discuss 2 unique medications: pramlintide, which is indicated for both type and type-2 diabetes, and colesevelam, which is approved by the United States Food and Drug Administration for both type-2 diabetes and hyperlipidemia. It will further review the clinical data on the novel emerging agents of sodium-glucose cotransporter-2 inhibitors, tagatose, and succinobucol, all currently in phase III clinical trials. This review article can serve as an aid for clinicians to identify clinical indications in which these new agents can be applied in the treatment algorithm.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Drug Design , Hypoglycemic Agents/therapeutic use , Algorithms , Allylamine/analogs & derivatives , Allylamine/pharmacology , Allylamine/therapeutic use , Animals , Colesevelam Hydrochloride , Diabetes Mellitus, Type 2/physiopathology , Hexoses/pharmacology , Hexoses/therapeutic use , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacology , Incretins/pharmacology , Incretins/therapeutic use , Islet Amyloid Polypeptide/pharmacology , Islet Amyloid Polypeptide/therapeutic use , Probucol/analogs & derivatives , Probucol/pharmacology , Probucol/therapeutic use , Sodium-Glucose Transporter 2 , Sodium-Glucose Transporter 2 InhibitorsABSTRACT
PURPOSE: Active hexose-correlated compound (AHCC), a standardized extract of cultured Lentinula edodes mycelia, exerts antitumor effects through anti-inflammatory and immune-modulatory functions. Adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy has not been established. The purpose of this study was to evaluate the efficacy and safety of AHCC as adjuvant therapy in patients with advanced HCC after curative hepatectomy. PATIENTS AND METHODS: The study design was single-armed, non-randomized, open (no one was blinded), and uncontrolled. Patients with HCC who underwent curative hepatectomy were treated with AHCC (1 g) 3 times daily orally for 2 years. The inclusion criteria were HCC diagnosed preoperatively as stages A and B of the Barcelona clinic liver cancer (BCLC) classification and alpha-fetoprotein × protein induced by vitamin K absence or antagonist II (PIVKA-II) ≥ 105 for stage A. RESULTS: A total of 29 patients were treated with AHCC, of which 25 (4 patients discontinued) were followed up. The 2-year recurrence-free survival rate after resection was 48% for those without discontinuations and 55.2% for all patients with a history of treatment. Serum albumin levels decreased to a minimum in the first postoperative month and gradually recovered to the preoperative level at 6 months. Almost no change in lymphocyte percentage was observed during follow-up. Inflammation-based prognostic scores were maintained at favorable levels after hepatectomy. Toxicity and adverse events were not observed in any patient. CONCLUSION: AHCC may be safe and effective in preventing HCC recurrence after curative hepatectomy, and further randomized trials of AHCC for its use in this setting are warranted.This clinical trial was registered in UMIN Clinical Trials Registry (ID UMIN000024396).
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Shiitake Mushrooms , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Hepatectomy , Hexoses/therapeutic use , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length. METHOD: Subjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). TREATMENT: The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. RESULTS: 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the group treated with melaleuca oil and lavender oil had an ovicidal efficacy of 44.4% (SD 23%) and the group treated with the "suffocation" pediculicide had an ovicidal efficacy of 68.3% (SD 38%). CONCLUSION: Ovicidal efficacy varied substantially among treatments, from 3.3% to 68.3%. The "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%) pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The "suffocation" pediculicide and TTO/LO are also highly efficacious against the crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be recommended as first line treatments.
Subject(s)
Insecticides/therapeutic use , Leptospermum , Lice Infestations/drug therapy , Melaleuca , Oils, Volatile/therapeutic use , Ovum/drug effects , Pediculus/drug effects , Phytotherapy , Plant Oils/therapeutic use , Scalp Dermatoses/drug therapy , Tea Tree Oil/therapeutic use , Acrylates/administration & dosage , Acrylates/pharmacology , Acrylates/therapeutic use , Animals , Benzyl Alcohol/administration & dosage , Benzyl Alcohol/pharmacology , Benzyl Alcohol/therapeutic use , Child , Child, Preschool , Double-Blind Method , Drug Combinations , Ethylamines/administration & dosage , Ethylamines/pharmacology , Ethylamines/therapeutic use , Eucalyptus , Eucalyptus Oil , Hexoses/administration & dosage , Hexoses/pharmacology , Hexoses/therapeutic use , Humans , Insecticides/administration & dosage , Insecticides/pharmacology , Lavandula , Lice Infestations/parasitology , Mineral Oil/administration & dosage , Mineral Oil/pharmacology , Mineral Oil/therapeutic use , Monoterpenes/administration & dosage , Monoterpenes/pharmacology , Monoterpenes/therapeutic use , Oils, Volatile/administration & dosage , Oils, Volatile/pharmacology , Ovum/growth & development , Pediculus/growth & development , Plant Oils/administration & dosage , Plant Oils/pharmacology , Polysorbates/administration & dosage , Polysorbates/pharmacology , Polysorbates/therapeutic use , Scalp Dermatoses/parasitology , Tea Tree Oil/administration & dosage , Tea Tree Oil/pharmacologyABSTRACT
A potentially important new drug for treating type 2 diabetes, tagatose, is now in phase 3 clinical trial. The history, development, additional health benefits, mechanisms of action and the potential for the drug are presented in context with a review of the rapidly growing epidemic of type 2 diabetes and treatments for it. An epimer of fructose, the natural hexose tagatose was originally developed by Spherix Incorporated (formerly Biospherics Inc.) as a low-calorie sugar substitute. Only 20% of orally ingested tagatose is fully metabolized, principally in the liver, following a metabolic pathway identical to that of fructose. Following a decade of studies, tagatose became generally recognized as safe for use in foods and beverages under US FDA regulation. The simple sugar is commercially produced by isomerization of galactose, which is prepared from lactose. Early human studies suggested tagatose as a potential antidiabetic drug through its beneficial effects on postprandial hyperglycaemia and hyperinsulinaemia. A subsequent 14-month trial confirmed its potential for treating type 2 diabetes, and tagatose showed promise for inducing weight loss and raising high-density lipoprotein cholesterol, both important to the control of diabetes and constituting benefits independent of the disease. Furthermore, tagatose was shown to be an antioxidant and a prebiotic, both properties cited in the maintenance and promotion of health. No current therapies for type 2 diabetes provide these multiple health benefits. The predominant side effects of tagatose are gastrointestinal disturbances associated with excessive consumption, generally accommodated within 1- to 2-week period. The health and use potentials for tagatose (branded Naturlose((R)) for this use) are given with respect to current type 2 diabetes drugs and markets. Under an FDA-affirmed protocol, Spherix is currently conducting a phase 3 trial to evaluate a placebo-subtracted treatment effect based on a decrease in HbA(1c) levels. Side effects, contraindications and possibly beneficial new findings will be carefully monitored. It is hoped that early results of the trial may become available by mid-2008. If a subsequent NDA is successful, tagatose may fill a major health need.
Subject(s)
Anti-Obesity Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hexoses/therapeutic use , Hypoglycemic Agents/therapeutic use , Obesity/prevention & control , Clinical Trials, Phase III as Topic , Double-Blind Method , Humans , Randomized Controlled Trials as TopicABSTRACT
The objective of the current research was to review and update evidence on the dietary effect of the consumption of tagatose in type 2 diabetes, as well as to elucidate the current approach that exists on its production and biotechnological utility in functional food for diabetics. Articles published before July 1, 2017, were included in the databases PubMed, EBSCO, Google Scholar, and Scielo, including the terms "Tagatose", "Sweeteners", "Diabetes Mellitus type 2", "Sweeteners", "D-Tag". D-Tagatose (D-tag) is an isomer of fructose which is approximately 90% sweeter than sucrose. Preliminary studies in animals and preclinical studies showed that D-tag decreased glucose levels, which generated great interest in the scientific community. Recent studies indicate that tagatose has low glycemic index, a potent hypoglycemic effect, and eventually could be associated with important benefits for the treatment of obesity. The authors concluded that D-tag is promising as a sweetener without major adverse effects observed in these clinical studies.
Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Hexoses/therapeutic use , Obesity/diet therapy , Sweetening Agents/therapeutic use , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/blood , Humans , Hypoglycemic Agents/blood , Hypoglycemic Agents/therapeutic use , Obesity/bloodABSTRACT
In the current study, we have tested the nonenzymatic glycation activities of ketohexoses, such as tagatose and psicose. Although tagatose-treated apoA-I (t-A-I) and psicose-treated apoA-I (p-A-I) exerted more inhibitory activity you cupric ion-mediated low-density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL) phagocytosis into macrophage than fructose-treated apoA-I (f-A-I). In the lipid-free state, t-A-I and f-A-I showed more multimerized band without crosslinking. Since t-A-I lost its phospholipid binding ability, the rHDL formation was not as successful as f-A-I. However, injecting t-A-I showed more antioxidant activities in zebrafish embryo under the presence of oxLDL. Three weeks of consumption of fructose (50% of wt in Tetrabit/4% cholesterol) showed a 14% elevation of serum triacylglycerol (TG), while tagatose-administered group showed 30% reduction in serum TG compared to high cholesterol control. Fructose-fed group showed the biggest area of Oil Red O staining with the intensity as strong as the HCD control. However, tagatose-consumed group showed much lesser Oil Red O-stained area with the reduction of lipid accumulation. In conclusion, although tagatose treatment caused modification of apoA-I, the functional loss was not as much severe as the fructose treatment in macrophage cell model, zebrafish embryo, and hypercholesterolemic zebrafish model.
Subject(s)
Apolipoprotein A-I/metabolism , Hexoses/therapeutic use , Hypercholesterolemia/genetics , Hyperlipidemias/genetics , Iron Chelating Agents/therapeutic use , Animals , Cholesterol , Hexoses/pharmacology , Hypercholesterolemia/metabolism , Hyperlipidemias/metabolism , Iron Chelating Agents/pharmacology , Oxidative Stress , ZebrafishABSTRACT
Spherix Inc (formerly Biospherics) is developing tagatose, an orally active lactose derivative for the potential treatment of obesity and type 2 diabetes. The compound is also under investigation for the potential treatment of anemia, hemophilia and medical problems related to infertility, birth weight and excessive maternal food intake. Phase I and II clinical trials have been completed.
Subject(s)
Anti-Obesity Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hexoses/therapeutic use , Hypoglycemic Agents/therapeutic use , Obesity/drug therapy , Animals , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/metabolism , Anti-Obesity Agents/pharmacokinetics , Anti-Obesity Agents/toxicity , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Contraindications , Hexoses/adverse effects , Hexoses/metabolism , Hexoses/pharmacokinetics , Hexoses/toxicity , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/toxicity , Structure-Activity RelationshipABSTRACT
Local destruction of malignant growths was achieved rapidly by creating around their cells a strongly hypertonic environment. Various hexoses, injected in and around tumors at 37 degrees, were utilized to produce the osmotic disturbance. Homeostatic correction of the osmotic disturbance was prevented by local ischemia, induced by vasoconstriction, and maintained soon afterwards by thrombosis. Of the few vasoactive agents tested for this purpose, serotonin was the safest and most effective. It worked better when mixed with the hexose than when injected separately s.c. at a distance. The best response to treatment was obtained from tumors which were unattached to deep structures, poorly vascularized, and resistant to an increase of internal pressure, whereas special precautions had to be taken with friable neoplasms to avoid dissemination of metastases. Under certain conditions, by causing acute tumor necrosis, a single treatment achieved a high ratio of cure; in which a favorable immune response to dramatic reduction of tumor burden and to resorbed lysed material perhaps played a part.
Subject(s)
Hexoses/therapeutic use , Neoplasms, Experimental/drug therapy , Serotonin/therapeutic use , Animals , Cell Adhesion , Female , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/pathology , Osmolar Concentration , Rats , Regional Blood Flow/drug effects , Vasoconstrictor Agents/administration & dosageABSTRACT
Restriction of dietary energy extends life and reduces incidences of disease in animals. These benefits would likely extend to humans. However, diet restriction in animals imposes reductions of 30-50% in food intake, which is probably unacceptable to humans. Low-energy sweeteners used in beverages offer minor reductions in energy intake. However, they lack the bulk required for baked goods and other sugar-rich foods. Full-bulk sweeteners providing about one-half the energy of sugar are under development for such uses. Laxation limits their acceptable dose. Even within such limitations, they can help achieve the health benefits for humans indicated by diet restriction. D-Tagatose, a new candidate sweetener, is nearly as sweet as sucrose and has the bulk of sucrose, yet provides zero available energy. We discuss its potential contribution to human diet restriction along with its specific effect in delaying the aging effects of glycosylation.
Subject(s)
Diet , Dietary Carbohydrates/metabolism , Health , Sweetening Agents/metabolism , Animals , Energy Metabolism , Hexoses/metabolism , Hexoses/therapeutic use , Humans , Sweetening Agents/administration & dosageABSTRACT
The synthesis of alpha-D-glucopyranosyl 1-(methylenediphosphonate) (11), alpha-D-galactopyranosyl 1-(methylenediphosphonate) (14), and alpha-D-mannopyranosyl 1-(methylenediphosphonate) (17) has been accomplished. [(Di-phenoxyphosphinyl)methyl]phosphonic acid (diphenyl-MDP) (5), synthesized by two different procedures, was fused with beta-D-glucopyranose pentaacetate followed by catalytic hydrogenation to give 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl methylenediphosphonate (glucose-MDP) (10). The anomeric configuration of 10 was assigned on the basis of NMR spectral studies. Condensation of 10 with 2',3'-di-O-acetyladenosine was accomplished by using 1-(mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT) as coupling agent, and removal of the blocking groups gave adenosine 5'-[(alpha-D-glucopyranosylhydroxyphosphinyl)methyl]phosphonate (20). Uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl] phosphonate (23) and guanosine 5'-[(alpha-D-mannopyranosylhydroxyphosphinyl)methyl]phosphonate (26) were similarly prepared. Using a specific glycoprotein galactosyltransferase (EC 2.4.1.38) assay, uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl]phosphonate (23) demonstrated competitive inhibition with an apparent Ki of 97 microM. The adenosine analogue did not inhibit the enzyme. None of the above compounds show any in vitro antitumor or antiviral activity. Such specific inhibitors of glycosyltransferases may serve as specific probes to study various glycosyltransferases that might be involved in the process of metastasis.
Subject(s)
Diphosphonates/chemical synthesis , Hexoses/chemical synthesis , Hexosyltransferases/antagonists & inhibitors , Nucleosides/chemical synthesis , Animals , Cell Line , Chemical Phenomena , Chemistry , Diphosphonates/pharmacology , Diphosphonates/therapeutic use , Hexoses/pharmacology , Hexoses/therapeutic use , Humans , Leukemia L1210/drug therapy , Leukemia, Lymphoid/drug therapy , Magnetic Resonance Spectroscopy , Mice , Molecular Conformation , Nucleosides/pharmacology , Nucleosides/therapeutic use , Structure-Activity Relationship , Viruses/drug effectsABSTRACT
4-Deoxy-4-fluoro-alpha-D-sorbose (6) was prepared in crystalline form by the action of potassium hydrogen fluoride on 3,4-anhydro-1,2-O-isopropylidene-beta-D-psicopyranose (3) followed by deacetonation. Under identical conditions, 3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose (7) underwent epoxide migration to give 4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose (12), which after deacetonation yielded 4-deoxy-4-fluoro-D-tagatose (15) and 5-deoxy-5-fluoro-alpha-L-sorbopyranose (16), the latter as the crystalline, free sugar. The action of glycol-cleavage reagents on the isopropylidene acetals of the deoxyfluoro sugars was consistent with the assigned structures. The structures were established by 13-C n.m.r. studies of the free deoxyfluoro sugars 6 and 16 and of the isopropylidene acetal 13, and by 1-H n.m.r. studies on the acetylated isopropylidene acetals 5 diacetate, 13 diacetate, and 14 diacetate. 5-Deoxy-5-fluoro-L-sorbose (16) was biologically active, producing in mice effects characteristic of deoxyfluorotrioses and of fluoroacetate. 4-Deoxy-4-fluoro-D-tagatose (15) and 4-deoxy-4-fluoro-D-sorbose (6) produced no apparent effects in mice up to a dose of 500mg/kg. The implications of these findings with respect to transport, phosphorylation, and the action of aldolase on ketohexoses are discussed.
Subject(s)
Deoxy Sugars/chemical synthesis , Antineoplastic Agents , Deoxy Sugars/therapeutic use , Fluorine/therapeutic use , Hexoses/therapeutic use , Lethal Dose 50 , Molecular Conformation , Neoplasms/drug therapy , Sorbose/therapeutic useABSTRACT
Six derivatives of sixteen-membered macrolides possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar were synthesized via 3"-methylthiomethyl ether intermediates in reasonable yield. Introduction of a methyl group on the 3"-hydroxyl group of midecamycin A1 was effective for enhancing its antibacterial activity. All these derivatives exhibited excellent therapeutic effects in mice, and some of them showed improved pharmacokinetics compared with the natural antibiotics (mycarose type) in mice. Facile synthesis of 9-O-acylated analogues are also described.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Hexoses/chemistry , Hexoses/therapeutic use , Animals , Anti-Bacterial Agents/chemical synthesis , Drug Evaluation, Preclinical , Drug Resistance, Microbial , Hexoses/chemical synthesis , Macrolides , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred ICR , Molecular Structure , Pneumococcal Infections/drug therapy , Staphylococcal Infections/drug therapyABSTRACT
There is evidence to suggest that the extra nuclear cell constituents are the part of the cell which contains all the biochemical mechanisms responsible for implementing all cell functions. These functions include control of cell division, growth, response to injury, replacement of effete cells, maintenance of anatomical and spatial cellular relations and specific cellular function and structure. The energy to perform these functions is derived from the aerobic metabolism of glucose. The energy required for nuclear division appears to be wholly or partly derived from the anaerobic metabolism of glucose. Ethyl alcohol interferes with the aerobic metabolic pathways and thus disrupts or diminishes all aerobically activated cell functions. The speed of all activities motivated by aerobic glycolysis can be increased by appropriate electrical stimulations delivered from any of a range of electromagnetic radiation frequencies tested. In addition to the stimulant effect on aerobic metabolic processes, 434 MHz can stimulate the anaerobic glucose metabolism of cancer with consequent stimulation of cancer growth rate. 434 MHz appears to deliver energy to the anaerobic cancer metabolism by causing a resonance phenomenon amongst one or more of the substrates which comprise the first few stages of glycolysis. This phenomenon permits the selective delivery of electromagnetic radiation energy to cancer cells which, if sufficiently intense, causes injury to cancer cells without harm to the normal cells except when the latter are in the phase of anaerobic metabolism which occurs at some stage of the mitotic cycle. Streptokinase, ethanol and glucose analogues increase the lethal effects on cancers undergoing therapy with 434 MHz radiation and observations of such responses suggest a theoretical basis to explain the rare spontaneous remissions of human cancer. Cancer appears to protect its glucose supplies by elevating the blood glucose levels above normal and by some mechanism which reduces the effectiveness of the body's control of its fasting glucose level. The serum fibrinogen level rises when cancer involves the abdominal viscerae, particularly the liver. A raised serum fibrinogen level appears to be a direct indication that the liver must be included in the treatment regime if longer survival is desired. If the level cannot be corrected then death of that individual appears assured.
Subject(s)
Cytoplasm/physiology , Electromagnetic Phenomena , Mitosis , Neoplasms/therapy , Adult , Aged , Azaserine/therapeutic use , Cell Division , Ethanol/therapeutic use , Female , Fibrinogen/metabolism , Hexoses/therapeutic use , Hot Temperature , Humans , Insulin/therapeutic use , Male , Middle Aged , Neoplasms/metabolism , Streptokinase/therapeutic use , Wound HealingABSTRACT
In this study, 28 patients with maintained beta-blockade underwent coronary artery bypass grafting. Twelve of these patients, who received preoperative infusion of carbohydrate-phosphate solution, had a smaller cumulated leakage of CK-B compared to the others, suggesting reduced myocardial damage.
Subject(s)
Coronary Artery Bypass , Heart Diseases/prevention & control , Adrenergic beta-Antagonists/therapeutic use , Creatine Kinase/blood , Electrolytes/therapeutic use , Female , Hexoses/therapeutic use , Humans , Intraoperative Complications/drug therapy , Male , Middle Aged , PremedicationABSTRACT
Tagatose, a low-calorie, full-bulk natural sugar, has just attained GRAS (Generally Recognized As Safe) status under U.S. Food and Drug Administration (FDA) regulations, thereby permitting its use as a sweetener in foods and beverages. This paper presents all current aspects of tagatose with respect to demonstrated food and beverage applications and the potential health and medical benefits of this unique substance. Summarized studies are referenced to detailed peer-reviewed papers. The safety studies followed the recommendations in the FDA "Red Book." Results were submitted to an Expert Panel for determination of GRAS status under FDA regulation. Small phase 2 clinical trials showed tagatose to be effective in treating type 2 diabetes. The results, buttressed by the references cited, support the efficacy of the various applications disclosed for tagatose. Tagatose has been found to be safe and efficacious for use as a low-calorie, full-bulk sweetener in a wide variety of foods, beverages, health foods, and dietary supplements. It fills broad, heretofore unmet needs for a low-calorie sweetener in products in which the bulk of sugar is important, such as chocolates, chewing gum, cakes, ice cream, and frosted cereals. Its synergism with high-intensity sweeteners also makes it useful in sodas. Various health and medical benefits are indicated, including the treatment of type 2 diabetes, hyperglycemia, anemia, and hemophilia and the improvement of fetal development.
Subject(s)
Diabetes Mellitus/diet therapy , Hexoses/pharmacokinetics , Sweetening Agents/pharmacokinetics , Consumer Product Safety , Food, Organic , Health , Hexoses/administration & dosage , Hexoses/therapeutic use , Humans , Legislation, Food , Safety , Sweetening Agents/administration & dosage , Sweetening Agents/therapeutic use , United States , United States Food and Drug AdministrationABSTRACT
In the paper, the results of clinical applications of a complex peroral therapeutic solution--gelvisol for symptomatic treatment of generalized malignant tumors of the breast, lung and thyroid are summarized. The solution was administered in a dose of 50-60 ml 5-6 times a day during 12-14 days. A positive effect was manifested in the improved general condition of patients, better appetite, less intoxication of the organisms, better functioning of the liver and kidneys.