WorldWideScience

Sample records for biguanides

  1. [Biguanide].

    Science.gov (United States)

    Ohta, Akio; Tanaka, Yasushi

    2015-03-01

    Metformin, a biguanide, is considered in EASD and ADA to be a first-line glucose-lowering agent for patients with type 2 diabetes. The effectiveness of metformin as an anti-diabetic drug is explained by its ability to lower blood glucose by decreasing hepatic glucose production, stimulating glucose uptake in the muscle, and increasing fatty acid oxidation in adipose tissue. The exact mechanism of this effect has not been fully understood, but metformin is thought to activate hepatic AMP-activated protein kinase (AMPK), and it suppresses liver glucagon signal by increasing AMP due to inhibition of mitochondrial respiratory complex I. Caution is advised to avoid use of metformin in patients at risk for lactic acidosis (e.g., in patients with advanced renal and liver insufficiency, infection, dehydration, alcoholism, or in those using diuretics or SGLT2 inhibitor).

  2. Comparing two polymeric biguanides: chemical distinction, antiseptic efficacy and cytotoxicity of polyaminopropyl biguanide and polyhexamethylene biguanide.

    Science.gov (United States)

    Rembe, Julian-Dario; Fromm-Dornieden, Carolin; Schäfer, Nadine; Böhm, Julia K; Stuermer, Ewa K

    2016-08-01

    In this study, polyaminopropyl biguanide (PAPB) was compared to the molecularly closely related polyhexamethylene biguanide (PHMB) with respect to chemical relationship, antiseptic efficacy and cytotoxicity in vitro. Cytotoxicity for human keratinocytes (HaCaTs) and murine fibroblasts (L929) was determined according to ISO EN 10993-5 for both substances. Antimicrobial efficacy tests were performed via determination of the MBC, quantitative suspension method for substances and investigation of two PAPB- or PHMB-containing dressings against Staphyloccoccus aureus, Escherichia coli and Pseudomonas aeruginosa, according to international standards. Prior mass spectrometry was performed for chemical differentiation of the investigated substances. PHMB showed high toxicity even in low concentrations for both tested cell lines and a high antimicrobial efficacy against S. aureus and E. coli. In the case of PAPB, no or only low cytotoxicity was detected after 72 h, whilst comparable antibacterial features are lacking, as PAPB showed no relevant antimicrobial effects. Even though chemically closely related, PAPB proved to be ineffective in bacterial eradication, whilst PHMB showed a high efficacy. The discovery and establishment of safe and effective alternative antiseptics are important issues for the treatment of infected wounds. In particular, rising bacterial resistances to established agents, as well as ongoing discussions of potential toxic or carcinogenic effects emphasize this necessity. Nevertheless, the presented results highlight that even small changes in the chemical structure of related agents such as PHMB and PAPB can dramatically affect their efficacy and, therefore, need to be carefully distinguished and assessed side by side.

  3. Insulin and longevity: antidiabetic biguanides as geroprotectors.

    Science.gov (United States)

    Anisimov, Vladimir N; Semenchenko, Anna V; Yashin, Anatoli I

    2003-01-01

    The results of previous experimental studies of effects of antidiabetic biguanides (phenformin and buformin) on life span and spontaneous tumor incidence in mice and rats were recalculated and reanalyzed using standard demographic models of mortality. The chronic treatment of female C3H/Sn mice with phenformin prolonged the mean life span by 21.1% (P biguanide, buformin, slightly increased their mean life span (by 7.3%; P > 0.05). The mean life span of the last 10% survivors increased by 12% (P biguanides slightly decreased the body weight, slowed down the age-related decline of the reproductive function in female rats. The results of our experiments provide evidence that antidiabetic biguanides are promising geroprotectors as well as drugs which can be used in the prevention of cancer.

  4. Phagocytosis Affects Biguanide Sensitivity of Acanthamoeba spp.

    Science.gov (United States)

    Noble, Judith A.; Ahearn, Donald G.; Avery, Simon V.; Crow Jr., Sidney A.

    2002-01-01

    The incidence of Acanthamoeba keratitis, a disease associated with contact lens wear, has been in apparent decline with the advent of multipurpose contact lens solutions. The concentrations of the biguanides chlorhexidine digluconate (CHX) and particularly polyhexamethylene biguanide (PHMB) included in multipurpose solutions (MPSs) are sublethal for amoebae. We evaluated by flow cytometry the effects of these two biguanides on phagocytosis of particles and the survival of trophozoites of Acanthamoeba castellanii and A. polyphaga. Trophozoites of A. castellanii and A. polyphaga (106/ml) were exposed to solutions of 5 and 50 μg of PHMB and CHX per ml in the presence and absence of particles (i.e., heat-killed yeasts and bacteria and latex beads). In addition, trophozoites were exposed to particles treated with these concentrations of the two biguanides. In the absence of particles, trophozoites of A. polyphaga appeared to be more resistant to the biguanides than those of A. castellanii. In the presence of particles, the rates of survival of both species were decreased. In most instances, particles treated with sublethal concentrations of both biguanides that were adsorbed onto the particles reduced the incidence of phagocytosis. Particles present in MPSs in contact lens cases may be involved in the decreased incidence of Acanthamoeba keratitis. PMID:12069957

  5. Phagocytosis affects biguanide sensitivity of Acanthamoeba spp.

    Science.gov (United States)

    Noble, Judith A; Ahearn, Donald G; Avery, Simon V; Crow, Sidney A

    2002-07-01

    The incidence of Acanthamoeba keratitis, a disease associated with contact lens wear, has been in apparent decline with the advent of multipurpose contact lens solutions. The concentrations of the biguanides chlorhexidine digluconate (CHX) and particularly polyhexamethylene biguanide (PHMB) included in multipurpose solutions (MPSs) are sublethal for amoebae. We evaluated by flow cytometry the effects of these two biguanides on phagocytosis of particles and the survival of trophozoites of Acanthamoeba castellanii and A. polyphaga. Trophozoites of A. castellanii and A. polyphaga (10(6)/ml) were exposed to solutions of 5 and 50 microg of PHMB and CHX per ml in the presence and absence of particles (i.e., heat-killed yeasts and bacteria and latex beads). In addition, trophozoites were exposed to particles treated with these concentrations of the two biguanides. In the absence of particles, trophozoites of A. polyphaga appeared to be more resistant to the biguanides than those of A. castellanii. In the presence of particles, the rates of survival of both species were decreased. In most instances, particles treated with sublethal concentrations of both biguanides that were adsorbed onto the particles reduced the incidence of phagocytosis. Particles present in MPSs in contact lens cases may be involved in the decreased incidence of Acanthamoeba keratitis.

  6. Serine deprivation enhances antineoplastic activity of biguanides.

    Science.gov (United States)

    Gravel, Simon-Pierre; Hulea, Laura; Toban, Nader; Birman, Elena; Blouin, Marie-José; Zakikhani, Mahvash; Zhao, Yunhua; Topisirovic, Ivan; St-Pierre, Julie; Pollak, Michael

    2014-12-15

    Metformin, a biguanide widely used in the treatment of type II diabetes, clearly exhibits antineoplastic activity in experimental models and has been reported to reduce cancer incidence in diabetics. There are ongoing clinical trials to evaluate its antitumor properties, which may relate to its fundamental activity as an inhibitor of oxidative phosphorylation. Here, we show that serine withdrawal increases the antineoplastic effects of phenformin (a potent biguanide structurally related to metformin). Serine synthesis was not inhibited by biguanides. Instead, metabolic studies indicated a requirement for serine to allow cells to compensate for biguanide-induced decrease in oxidative phosphorylation by upregulating glycolysis. Furthermore, serine deprivation modified the impact of metformin on the relative abundance of metabolites within the citric acid cycle. In mice, a serine-deficient diet reduced serine levels in tumors and significantly enhanced the tumor growth-inhibitory actions of biguanide treatment. Our results define a dietary manipulation that can enhance the efficacy of biguanides as antineoplastic agents that target cancer cell energy metabolism.

  7. Potential applications for biguanides in oncology.

    Science.gov (United States)

    Pollak, Michael

    2013-09-01

    Metformin is widely prescribed for the treatment of type II diabetes. Recently, it has been proposed that this compound or related biguanides may have antineoplastic activity. Biguanides may exploit specific metabolic vulnerabilities of transformed cells by acting on them directly, or may act by indirect mechanisms that involve alterations of the host environment. Preclinical data suggest that drug exposure levels are a key determinant of proposed direct actions. With respect to indirect mechanisms, it will be important to determine whether recently demonstrated metformin-induced changes in levels of candidate systemic mediators such as insulin or inflammatory cytokines are of sufficient magnitude to achieve therapeutic benefit. Results of the first generation of clinical trials now in progress are eagerly anticipated. Ongoing investigations may justify a second generation of trials that explore pharmacokinetic optimization, rational drug combinations, synthetic lethality strategies, novel biguanides, and the use of predictive biomarkers.

  8. [Lactic acidosis and biguanid therapy (author's transl)].

    Science.gov (United States)

    Thimme, W; Buschmann, H J; Dissmann, W; Amft, R

    1976-09-03

    Ten case histories of patients with lactic acidosis and biguanide therapy are presented. 6 patients received phenformin, 4 buformin. The symptomatology was characterized by somnolence or unconsciousness with hyperventilation, renal insufficiency, signs of infection occasionally with detection of gram negative rods and in later stages circulatory insufficiency with high central venous pressure. Glucose, insulin, bicarbonate, dialysis, antibiotics and katecholamines were the therapeutic measurements. It is the proposal of this communication to call attention again to the potential toxicity of biguanids which makes necessary the strict observation of contraindications.

  9. A direct access to heptasubstituted biguanides.

    Science.gov (United States)

    Yavari, Issa; Nematpour, Manijeh

    2015-11-01

    An efficient and experimentally simple copper-catalyzed carbon-nitrogen bond formation for the synthesis of [Formula: see text]-arylated biguanides starting from aryl halides, carbodiimides, and 1,1,3,3-tetramethylguanidine is reported. The potential diversity of this type of reaction, easily available starting materials, and commercially available low-cost catalysts are the incremental features of this methodology.

  10. [Clinical difference between thiazolidinediones and biguanides].

    Science.gov (United States)

    Hotta, N

    2001-11-01

    Hyperglycemia in patients with type 2 diabetes mellitus is caused by peripheral insulin resistance, which results in decreased insulin-mediated glucose disposal and increased endogenous glucose production, and inadequate insulin secretion. Recently, either biguanides or thiazolidinediones among oral hypoglycemic agents is widely used to patients with type 2 diabetes mellitus for reversal of insulin resistance. As clinical difference between biguanides and thiazolidinediones in reducing blood glucose, the former primarily lowers endogenous glucose production presumably at the level of liver, whereas the latter increases insulin-mediated peripheral glucose disposal, which occurs predominantly in skeletal muscle. Therefore, combination therapy with these two drugs results in further improvement in glucose control. Combination therapy including these two drugs is attractive prospects in future treatment for patients with type 2 diabetes.

  11. Biguanide-Atovaquone Synergy against Plasmodium falciparum In Vitro

    OpenAIRE

    2002-01-01

    The synergistic potential of a range of biguanides, their triazine metabolites, tetracyclines, and pyrimethamine in combination with atovaquone has been assessed. All five biguanides tested interacted synergistically with atovaquone against Plasmodium falciparum in vitro. All of the other compounds tested were either additive or antagonistic.

  12. Biguanide related compounds in traditional antidiabetic functional foods.

    Science.gov (United States)

    Perla, Venu; Jayanty, Sastry S

    2013-06-01

    Biguanides such as metformin are widely used worldwide for the treatment of type-2 diabetes. The identification of guanidine and related compounds in French lilac plant (Galega officinalis L.) led to the development of biguanides. Despite of their plant origin, biguanides have not been reported in plants. The objective of this study was to quantify biguanide related compounds (BRCs) in experimentally or clinically substantiated antidiabetic functional plant foods and potatoes. The corrected results of the Voges-Proskauer (V-P) assay suggest that the highest amounts of BRCs are present in green curry leaves (Murraya koenigii (L.) Sprengel) followed by fenugreek seeds (Trigonella foenum-graecum L.), green bitter gourd (Momordica charantia Descourt.), and potato (Solanum tuberosum L.). Whereas, garlic (Allium sativum L.), and sweet potato (Ipomea batatas (L.) Lam.) contain negligible amounts of BRCs. In addition, the possible biosynthetic routes of biguanide in these plant foods are discussed.

  13. Liver uptake of biguanides in rats.

    Science.gov (United States)

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko

    2011-09-01

    Metformin is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus. The liver is the primary target, metformin being taken up into human and rat hepatocytes via an active transport mechanism. The present study was designed to compare hepatic uptake of two biguanides, metformin and phenformin, in vitro and in vivo. In in vitro experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited a much higher affinity and transport than metformin, with marked differences in kinetics. The K(m) values for metformin and phenformin were 404 and 5.17μM, respectively, with CLint (V(max)/K(m)) values 1.58μl/min per 10(6) cells and 34.7μl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver concentrations of radioactivity at 0.5 hour after dosing were 21.5μg eq./g with metformin but 147.1μg eq./g for phenformin, ratios of liver to plasma concentrations being 4.2 and 61.3, respectively. In conclusion, the results suggest that uptake of biguanides by rat hepatocytes is in line with the liver distribution found in vivo, phenformin being more efficiently taken up by liver than metformin after oral administration.

  14. Selective Inhibition of Deactivated Mitochondrial Complex I by Biguanides

    OpenAIRE

    2015-01-01

    Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates, but is rapidly and fully reversed to the active state in the presence of NADH....

  15. Transport of biguanides by human organic cation transporter OCT2.

    Science.gov (United States)

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko; Takano, Mikihisa

    2013-06-01

    Biguanides have the severe side effect of lactic acidosis. Although both metformin and phenformin are biguanide derivatives, there is a difference in the frequency at which they induce lactic acidosis. However, the reasons for the difference are not clear. Metformin has been reported to be mainly excreted into urine by human organic cation transporter 2 (hOCT2). The present study was designed to investigate the renal transport of metformin and phenformin, focusing on hOCT2, using hOCT2-expressing oocytes. Both biguanides were found to be good substrates for hOCT2. However, phenformin exhibited a higher affinity and transport activity than metformin. The Km values for metformin and phenformin were 235 and 37.4 μM, with CL(int) (V(max)/K(m)) values of 71.9×10⁻³ μL/min per oocyte and 209×10⁻³ μL/min per oocyte, respectively. This is the first report that has compared the transport profiles of these biguanides in hOCT2-expressing oocytes. The results suggest that plasma concentration of phenformin in subjects carrying hOCT2 variant may be higher compared to reference subjects, as reported in metformin. In addition, the relationship between plasma concentration of these biguanides and blood lactate level as well as the possible reasons for the difference in the associated frequency of occurrence of lactic acidosis are discussed.

  16. Metformin and other biguanides in oncology: advancing the research agenda.

    Science.gov (United States)

    Pollak, Michael

    2010-09-01

    Retrospective studies that may be impractical to confirm prospectively suggest that diabetics treated with metformin have a substantially reduced cancer burden compared with other diabetics. It is unclear if this reflects a chemopreventive effect, an effect on transformed cells, or both. It also remains to be established if these data have relevance to people without diabetes. Laboratory models, however, provide independent impressive evidence for the activity of metformin and other biguanides in both cancer treatment and chemoprevention. Investigations of mechanisms of action of biguanides have revealed considerable complexity and have identified important gaps in knowledge that should be addressed to ensure the optimal design of clinical trials of these agents. Such trials may define important new indications for biguanides in the prevention and/or treatment of many common cancers.

  17. Selective inhibition of deactivated mitochondrial complex I by biguanides.

    Science.gov (United States)

    Matsuzaki, Satoshi; Humphries, Kenneth M

    2015-03-24

    Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate-limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates but is rapidly and fully reversed to the active state in the presence of NADH. The objective of this study was to determine the relative sensitivity of active/de-active complex I to biguanide-mediated inhibition and resulting superoxide radical (O₂(•⁻)) production. Using isolated rat heart mitochondria, we show that deactivation of complex I sensitizes it to metformin and phenformin (4- and 3-fold, respectively), but not to other known complex I inhibitors, such as rotenone. Mitochondrial O₂(•⁻) production by deactivated complex I was measured fluorescently by NADH-dependent 2-hydroxyethidium formation at alkaline pH to impede reactivation. Superoxide production was 260.4% higher than in active complex I at pH 9.4. However, phenformin treatment of de-active complex I decreased O₂(•⁻) production by 14.9%, while rotenone increased production by 42.9%. Mitochondria isolated from rat hearts subjected to cardiac ischemia, a condition known to induce complex I deactivation, were sensitized to phenformin-mediated complex I inhibition. This supports the idea that the effects of biguanides are likely to be influenced by the complex I state in vivo. These results demonstrate that the complex I active and de-active states are a determinant in biguanide-mediated inhibition.

  18. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria.

    Science.gov (United States)

    Bridges, Hannah R; Jones, Andrew J Y; Pollak, Michael N; Hirst, Judy

    2014-09-15

    The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the molecular interaction(s) between metformin and complex I remain uncharacterized. In the present paper, we describe the effects of five pharmacologically relevant biguanides on oxidative phosphorylation in mammalian mitochondria. We report that biguanides inhibit complex I by inhibiting ubiquinone reduction (but not competitively) and, independently, stimulate reactive oxygen species production by the complex I flavin. Biguanides also inhibit mitochondrial ATP synthase, and two of them inhibit only ATP hydrolysis, not synthesis. Thus we identify biguanides as a new class of complex I and ATP synthase inhibitor. By comparing biguanide effects on isolated complex I and cultured cells, we distinguish three anti-diabetic and potentially anti-neoplastic biguanides (metformin, buformin and phenformin) from two anti-malarial biguanides (cycloguanil and proguanil): the former are accumulated into mammalian mitochondria and affect oxidative phosphorylation, whereas the latter are excluded so act only on the parasite. Our mechanistic and pharmacokinetic insights are relevant to understanding and developing the role of biguanides in new and existing therapeutic applications, including cancer, diabetes and malaria.

  19. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase

    OpenAIRE

    2016-01-01

    Abstract Background The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closel...

  20. Use of biguanides and the risk of colorectal cancer: a register-based cohort study.

    Science.gov (United States)

    Knapen, Lotte M; Dittrich, Suzanne T A M; de Vries, Frank; Starup-Linde, Jakob; Vestergaard, Peter; Henry, Ronald M A; Stolk, Leo M L; Neef, Cees; Bazelier, Marloes T

    2013-11-01

    Observational studies have shown conflicting results on the potential protecting effect of biguanide use with the risk of colorectal neoplasms. In addition, the cellular mechanism can either support or oppose biguanides influence on colorectal carcinoma. Our objective was to evaluate the association between biguanide use and colorectal carcinoma. A population-based cohort study using healthcare data from the Danish National database (1996-2007), was conducted. Oral antidiabetic drug users (n = 177,281) were matched 1:3 with a population-based reference group. Cox proportional hazard models estimated hazard ratios (HRs) of colorectal carcinoma. Stratification was performed to analyse the risk of colorectal cancer in current biguanide users. Two sub-analyses were performed, to investigate the risk of colorectal cancer associated with discontinuous and prolonged use of biguanides. Instead of a protective effect, we found that current biguanide users had a 1.2-fold increased risk of colorectal cancer (HR = 1.19, 95% CI = 1.08-1.30) as compared with the non-diabetes reference group. Prolonged use was not inversely associated with colorectal cancer either. When studying colorectal risk with biguanides, the underlying T2DM should be taken into account since a 1.3-1.6-fold increased risk was found in oral antidiabetic drug users compared to controls unexposed to diabetic medication. This study could not detect a protective effect of biguanide use with colorectal cancer. Therefore, this study does not support a further investigation of the effectiveness of biguanides to prevent colorectal carcinoma in clinical studies.

  1. [Effect of biguanids on the lactate metabolism. Studies in diabetics under submaximal ergometric exercise (author's transl)].

    Science.gov (United States)

    Pilger, E; Schmid, P; Goebel, R

    1979-06-01

    24 diabetics without any complications were subjected to an exercise test before and after biguanid therapy. The schedule of the physical strain was a modification of the Kaltenbach diagram. Changes of lactate, pyruvate, pH-standard bicarbonate and base excess values were analysed. Additionally to antidiabetical therapy each of the 8 patients was given either metformin or buformin or phenformin now. Each one of the biguanid derivates induced a rise of the lactate level before and after the exercise test. Phenformin showed the greatest influence on the lactate metabolism, metformin the smallest. Reasons causing the lactogene effect and the quantitative differences of the biguanides are discussed.

  2. Physical and Chemical Characterization of Poly(hexamethylene biguanide Hydrochloride

    Directory of Open Access Journals (Sweden)

    Luiz Henrique C. Mattoso

    2011-06-01

    Full Text Available We present the characterization of commercially available Poly(hexamethylene biguanide hydrochloride (PHMB, a polymer with biocidal activity and several interesting properties that make this material suitable as a building block for supramolecular chemistry and “smart” materials. We studied polymer structure in water solution by dynamic light scattering, surface tension and capacitance spectroscopy. It shows typical surfactant behavior due to amphiphilic structure and low molecular weight. Spectroscopic (UV/Vis, FT-NIR and thermal characterization (differential scanning calorimetry, DSC, and thermogravimetric analysis, TGA were performed to give additional insight into the material structure in solution and solid state. These results can be the foundation for more detailed investigations on usefulness of PHMB in new complex materials and devices.

  3. Double-Biguanide Therapy for Resistant Acanthamoeba Keratitis

    Directory of Open Access Journals (Sweden)

    Giulio Ferrari

    2011-11-01

    Full Text Available Aims: To report the clinical and diagnostic findings of a patient with Acanthamoeba keratitis resistant to both polyhexamethylene biguanide (PHMB-hexamidine and chlorhexidine-hexamidine treatment. Methods: Slit-lamp biomicroscopy, corneal cell scraping and histopathology were performed on a 39-year-old woman presenting with corneal ulcer in her left eye. Results: The patient was successfully treated with PHMB-chlorhexidine association therapy. Subsequent perforating keratoplasty remained clear at the last follow-up visit after 7 months and increased visual acuity to 20/20 with correction. Conclusions: This case emphasizes the proteiform aspects of Acanthamoeba drug resistance, and suggests that PHMB-chlorhexidine association might represent an additional option for cases resistant to standard therapy.

  4. [Therapeutic utility of biguanides in the treatment of NIDDM].

    Science.gov (United States)

    Fujimoto, S

    1999-03-01

    Metformin, one of the biguanides, is an oral hypoglycemic agent which acts primarily by decreasing hepatic glucose output and by increasing peripheral glucose disposal, therefore it has different hypoglycemic mechanism from that of sulfonylureas. The hypoglycemic effects of metformin are observed not only in obese NIDDM patients, but also in non-obese NIDDM patients. Moreover, addition of metformin improves glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy. Therefore, it is complementary to sulfonylurea therapy and represents a useful additional drug for the treatment, irrespective of obesity. The rare but serious condition of lactic acidosis should be kept in mind as a potential side effect, however, if metformin is avoided in patients with contraindications, the medication is very safe.

  5. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria

    OpenAIRE

    2014-01-01

    The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the molecular interaction(s) between metformin and complex I remain uncharacterized. In the present paper, we describe the effects of five pharmacologically relevant biguanides on oxidative phosphorylation in...

  6. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase

    OpenAIRE

    2016-01-01

    Background The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closely related and both inhibit isolated complex I. Proguanil does not...

  7. Regulation of the Proliferation of Colon Cancer Cells by Compounds that Affect Glycolysis, Including 3-Bromopyruvate, 2-Deoxyglucose and Biguanides

    OpenAIRE

    Lea, Michael A.; Qureshi, Mehreen S.; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; desBordes, Charles

    2013-01-01

    In previous studies we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation but the effect was not always additive to that of biguanides and an additive effect was more notable i...

  8. Development of a fast atom bombardment tandem mass spectrometric screening method for alkyl-ended oligomeric biguanides

    Science.gov (United States)

    Monaghan, J. J.; Morden, W. E.

    1992-12-01

    The FAB-MS and FAB-MS---MS behaviour of a series of "alkyl-ended" oligomeric biguanides has been studied. MS---MS product ion scans showed that fragmentation of these species occurred by predictable cleavages of the biguanide chains. Results are presented from a number of MS---MS precursor ion and neutral loss scans studied in an attempt to develop a screening method for biguanides in complex mixtures. The most effective of these scans is shown to be the neutral loss of the N-alkylguanidine molecule. Use of this scan is demonstrated for a mixture of oligomeric biguanides.

  9. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs.

    Science.gov (United States)

    Hsu, Chia-Chi; Wu, Ling-Chia; Hsia, Cheng-Yuan; Yin, Pen-Hui; Chi, Chin-Wen; Yeh, Tien-Shun; Lee, Hsin-Chen

    2015-09-01

    Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients. However, whether alteration of energy metabolism is involved in regulating the sensitivity of HCC to biguanide drugs is still unclear. In the present study, we treated four HCC cell lines with mitochondrial inhibitors (rotenone and oligomycin) and biguanide drugs (metformin and phenformin), and found that the HCC cells which had a higher mitochondrial respiration rate were more sensitive to these treatments; whereas the HCC cells which exhibited higher glycolysis were more resistant. When glucose was replaced by galactose in the medium, the altered energy metabolism from glycolysis to mitochondrial respiration in the HCC cells enhanced the cellular sensitivity to mitochondrial inhibitors and biguanides. The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides. In conclusion, our results suggest that increased mitochondrial oxidative metabolism upregulates the sensitivity of HCC to biguanide drugs. Enhancing the mitochondrial oxidative metabolism in combination with biguanide drugs may be a therapeutic strategy for HCC.

  10. Metformin (dimethyl-biguanide induced DNA damage in mammalian cells

    Directory of Open Access Journals (Sweden)

    Rubem R. Amador

    2012-01-01

    Full Text Available Metformin (dimethyl-biguanide is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays and in mice (micronucleus assays. Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

  11. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    Energy Technology Data Exchange (ETDEWEB)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Pollak, Michael [Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada); Gotlieb, Walter H., E-mail: walter.gotlieb@mcgill.ca [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. Black-Right-Pointing-Pointer Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. Black-Right-Pointing-Pointer Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. Black-Right-Pointing-Pointer Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  12. Comparison of gene expression changes induced by biguanides in db/db mice liver.

    Science.gov (United States)

    Heishi, Masayuki; Hayashi, Koji; Ichihara, Junji; Ishikawa, Hironori; Kawamura, Takao; Kanaoka, Masaharu; Taiji, Mutsuo; Kimura, Toru

    2008-08-01

    Large-scale clinical studies have shown that the biguanide drug metformin, widely used for type 2 diabetes, to be very safe. By contrast, another biguanide, phenformin, has been withdrawn from major markets because of a high incidence of serious adverse effects. The difference in mode of action between the two biguanides remains unclear. To gain insight into the different modes of action of the two drugs, we performed global gene expression profiling using the livers of obese diabetic db/db mice after a single administration of phenformin or metformin at levels sufficient to cause a significant reduction in blood glucose level. Metformin induced modest expression changes, including G6pc in the liver as previously reported. By contrast, phenformin caused changes in expression level of many additional genes. We used a knowledge-based bioinformatic analysis to study the effects of phenformin. Differentially expressed genes identified in this study constitute a large gene network, which may be related to cell death, inflammation or wound response. Our results suggest that the two biguanides show a similar hypoglycemic effect in db/db mice, but phenformin induces a greater stress on the liver even a short time after a single administration. These findings provide a novel insight into the cause of the relatively high occurrence of serious adverse effect after phenformin treatment.

  13. Poly(alkylene biguanides) as proton conductors for high-temperature PEMFCs

    Energy Technology Data Exchange (ETDEWEB)

    Britz, Jochen; Meyer, Wolfgang H.; Wegner, Gerhard [Max Planck Institute for Polymer Research, Mainz (Germany)

    2010-02-23

    Poly(alkylene biguanides) are novel high-temperature proton conductors. This long-known class of polymers is presented as surprisingly stable high-temperature proton-conducting materials in the form of water-free HCl conjugates. Proton conductivity is dominated by free volume relaxation. Application in the context of fuel-cell membranes is discussed. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  14. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides.

    Science.gov (United States)

    Segal, Eric D; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua; Pollak, Michael; Gotlieb, Walter H

    2011-11-04

    Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  15. In vitro biological evaluation of biguanides and dihydrotriazines against Brugia malayi and folate reversal studies.

    Science.gov (United States)

    Bag, Seema; Tawari, Nilesh R; Sharma, Richa; Goswami, Kalyan; Reddy, M V R; Degani, Mariam S

    2010-01-01

    Dihydrofolate reductase (DHFR) is a well-known target for antibacterial and anticancer therapy. DHFR inhibitors are useful for protozoan parasites, but are yet to be explored against metazoan species; hence the present work was designed to evaluate the efficacy of DHFR inhibitors against filariasis, one of the major neglected tropical diseases. Molecules from our in-house library of synthetic antifolate agents (biguanide and dihydrotriazine derivatives) were evaluated along with the antimalarial drug pyrimethamine and the antibacterial drug trimethoprim in an in vitro model against Brugia malayi microfilariae (Mf). Three biguanides and two dihydrotriazines were more potent than trimethoprim and pyrimethamine against B. malayi Mf. Trimethoprim, pyrimethamine and four of the five compounds active against Mf were also active against adult worms. To probe the mechanism of action of the compounds, reversal of activity of active compounds by folic acid and folinic acid was studied. In conclusion, DHFR inhibitors could be used as leads for new antifilarial drugs.

  16. The Antimicrobial Activity of Wool Fabrics Treated with Crosslinking Agents and Polyhexamethylene Biguanide

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue; HE JINxin; ZHAN Yizhen

    2009-01-01

    @@ In this study, we used citric acid (CA) as a crosslinking agent, mixed with polyhexamethylene biguanide, to perform a pad-dry-cure treatment on wool fabrics to study its antimicrobial effects and physical properties. The surface characteristic and the structure of wool fabric were investigated by means of scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) was employed to study the crosslinking mechanism of the treated fabric.

  17. Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

    Science.gov (United States)

    Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

    2016-01-01

    Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

  18. Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties.

    Science.gov (United States)

    Drahota, Z; Palenickova, E; Endlicher, R; Milerova, M; Brejchova, J; Vosahlikova, M; Svoboda, P; Kazdova, L; Kalous, M; Cervinkova, Z; Cahova, M

    2014-01-01

    In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca(2+) ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.

  19. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells.

    Science.gov (United States)

    Orecchioni, Stefania; Reggiani, Francesca; Talarico, Giovanna; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Noonan, Douglas M; Dallaglio, Katiuscia; Albini, Adriana; Bertolini, Francesco

    2015-03-15

    The human white adipose tissue (WAT) contains progenitors with cooperative roles in breast cancer (BC) angiogenesis, local and metastatic progression. The biguanide Metformin (Met), commonly used for Type 2 diabetes, might have activity against BC and was found to inhibit angiogenesis in vivo. We studied Met and another biguanide, phenformin (Phe), in vitro and in vivo in BC models. In vitro, biguanides activated AMPK, inhibited Complex 1 of the respiratory chain and induced apoptosis of BC and WAT endothelial cells. In coculture, biguanides inhibited the production of several angiogenic proteins. In vivo, biguanides inhibited local and metastatic growth of triple negative and HER2+ BC in immune-competent and immune-deficient mice orthotopically injected with BC. Biguanides inhibited local and metastatic BC growth in a genetically engineered murine model model of HER2+ BC. In vivo, biguanides increased pimonidazole binding (but not HIF-1 expression) of WAT progenitors, reduced tumor microvessel density and altered the vascular pericyte/endothelial cell ratio, so that cancer vessels displayed a dysplastic phenotype. Phe was significantly more active than Met both in vitro and in vivo. Considering their safety profile, biguanides deserve to be further investigated for BC prevention in high-risk subjects, in combination with chemo and/or targeted therapy and/or as post-therapy consolidation or maintenance therapy for the prevention of BC recurrence.

  20. Biguanide-functionalized mesoporous SBA-15 silica as an efficient solid catalyst for interesterification of vegetable oils.

    Science.gov (United States)

    Xie, Wenlei; Hu, Libing

    2016-04-15

    The biguanide-functionalized SBA-15 materials were fabricated by grafting of organic biguanide onto the SBA-15 silica through covalent attachments, and then this organic-inorganic hybrid material was employed as solid catalysts for the interesterification of triacylglycerols for the modification of vegetable oils. The prepared catalyst was characterized by FTIR, XRD, SEM, TEM, nitrogen adsorption-desorption and elemental analysis. The biguanide base was successfully tethered onto the SBA-15 silica with no damage to the ordered mesoporous structure of the silica after the organo-functionalization. The solid catalyst had stronger base strength and could catalyze the interesterification of triacylglycerols. The fatty acid compositions and triacylglycerol profiles of the interesterified products were noticeably varied following the interesterification. The reaction parameters, namely substrate ratio, reaction temperature, catalyst loading and reaction time, were investigated for the interesterification of soybean oil with methyl decanoate. The catalyst could be reused for at least four cycles without significant loss of activity.

  1. Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

    Science.gov (United States)

    Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

    2013-02-01

    In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.

  2. Biological and spectral studies of O-Tolyl Biguanide: Experimental and theoretical approach

    Science.gov (United States)

    Beaula, T. Joselin; Muthuraja, P.; Sethuram, M.; Dhandapani, M.; Rastogi, V. K.; Jothy, V. Bena

    2017-01-01

    Antibiotic and antimicrobial compound O-Tolyl Biguanide (OTB) structure was calculated at the B3LYP using 6-311++G(d,p) basis set level of theory. Optimized geometric bond lengths, bond angles and dihedral angles of the molecule were calculated and analyzed. FT-IR and FT-Raman spectra of OTB were recorded and vibrational assignments of the observed fundamental bands had been proposed on the basis of peak positions and relative intensities. Molecular geometry, vibrational spectra, covalent bond orders and atomic charges of OTB had been used to investigate the effects of charge delocalization leading to Y-aromaticity.

  3. Blockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides.

    Science.gov (United States)

    Ortiz, Mario I

    2011-07-01

    There is evidence that administration of sulfonylureas, such as glibenclamide and tolbutamide, blocks diclofenac-induced antinociception, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the interaction between diclofenac and other hypoglycemic drugs, such as the biguanides metformin or phenformin. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, as well as two biguanides, metformin and phenformin, have any effect on the systemic antinociception that is induced by diclofenac and indomethacin using the rat formalin test as an animal model. Systemic injections of diclofenac (10 to 30mg/kg) and indomethacin (10 to 30mg/kg) produced dose-dependent antinociception during the second phase of the test. Systemic pretreatment with glibenclamide (3 and 10mg/kg), glipizide (3 and 10mg/kg), metformin (100 and 180mg/kg) or phenformin (100 and 180mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P0.05). These data suggest that diclofenac, but not indomethacin, activated K(+) channels and metformin and phenformin-dependent mechanisms, which resulted in systemic antinociceptive effects in the rat formalin test.

  4. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP.

    Science.gov (United States)

    Miller, Russell A; Chu, Qingwei; Xie, Jianxin; Foretz, Marc; Viollet, Benoit; Birnbaum, Morris J

    2013-02-14

    Glucose production by the liver is essential for providing a substrate for the brain during fasting. The inability of insulin to suppress hepatic glucose output is a major aetiological factor in the hyperglycaemia of type-2 diabetes mellitus and other diseases of insulin resistance. For fifty years, one of the few classes of therapeutics effective in reducing glucose production has been the biguanides, which include phenformin and metformin, the latter the most frequently prescribed drug for type-2 diabetes. Nonetheless, the mechanism of action of biguanides remains imperfectly understood. The suggestion a decade ago that metformin reduces glucose synthesis through activation of the enzyme AMP-activated protein kinase (AMPK) has recently been challenged by genetic loss-of-function experiments. Here we provide a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. In mouse hepatocytes, metformin leads to the accumulation of AMP and related nucleotides, which inhibit adenylate cyclase, reduce levels of cyclic AMP and protein kinase A (PKA) activity, abrogate phosphorylation of critical protein targets of PKA, and block glucagon-dependent glucose output from hepatocytes. These data support a mechanism of action for metformin involving antagonism of glucagon, and suggest an approach for the development of antidiabetic drugs.

  5. Comparison of potential risks of lactic acidosis induction by biguanides in rats.

    Science.gov (United States)

    Bando, Kiyoko; Ochiai, Shoko; Kunimatsu, Takeshi; Deguchi, Jiro; Kimura, Juki; Funabashi, Hitoshi; Seki, Takaki

    2010-10-01

    Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level.

  6. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

    Science.gov (United States)

    Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

    2014-04-01

    As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

  7. Mixed-ligand complex formation equilibria of CuII with biguanide in presence of glycine as the auxiliary ligand

    Indian Academy of Sciences (India)

    Tannistha Roy Barman; G N Mukherjee

    2006-09-01

    Equilibrium study on the mixed ligand complex formation of CuII with biguanide(Bg) and glycine (HG), indicated the formation of the complexes: Cu(Bg)2+, Cu(Bg)$_{2}^{2+}$, Cu(Bg-H)(Bg)+, Cu(Bg-H)2, Cu(Bg)(OH)+, Cu(Bg-H)(OH); Cu(G)+, Cu(G)(OH), Cu(G)2; Cu(G)(Bg)+, Cu(G)(Bg-H); (G)Cu(Bg)Cu(G)2+, (G)Cu(Bg-H)Cu(G)+, and (G)Cu(Bg-2H)Cu(G). From the deprotonation constants of coordinated biguanide (Bg) in the complexes Cu(Bg)(OH)+, Cu(Bg-H)(Bg)+ and Cu(G)(Bg)+, the Lewis basicities of the coordinated ligand species (Bg-H)-, OH- and glycinate (G-) were found to be of the order: (Bg-H)- >> OH- > G-. Bridging (N1-N4, N2-N5) tetradentate mode of coordination by biguanide species Bg, (Bg-H)- and (Bg-2H)2- was indicated from the occurrence of biguanide-bridged dinuclear mixed ligand complexes (G)Cu(Bg)Cu(G)2+, (G)Cu(Bg-H)Cu(G)+, (G)Cu(Bg-2H)Cu(G) in the complexation equilibria.

  8. Does atorvastatin work more effectively than biguanides in reducing cardiovascular risk factors?

    Science.gov (United States)

    Siddiq, Afshan; Khan, Rafeeq Alam; Baig, Sadia Ghousia

    2011-04-01

    Increased risk of coronary artery disease in diabetic persons is associated with increased level of lipoproteins. Usually, such risks are reverted with glycemic control by antidiabetic medicines in Type I diabetes millitus. However, in Type II diabetes mellitus lipid values can be improved using antidiabetics but still the risk of coronary artery disease remains. The initial approach for reducing lipid contents in diabetic patients should include glycemic control, diet, weight loss, and exercise. But if it fails then lipid-lowering agents like fibrate and HMG CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) inhibitors should work effectively. In the present study results of atorvastatin compared with biguanides proved atorvastatin as a more effective lipid-lowering agent along with antidiabetic activity so it can effectively help in reducing the risk of cardiovascular disease (CVD).

  9. Does atorvastatin work more effectively than biguanides in reducing cardiovascular risk factors?

    Directory of Open Access Journals (Sweden)

    Afshan Siddiq

    2011-01-01

    Full Text Available Increased risk of coronary artery disease in diabetic persons is associated with increased level of lipoproteins. Usually, such risks are reverted with glycemic control by antidiabetic medicines in Type I diabetes millitus. However, in Type II diabetes mellitus lipid values can be improved using antidiabetics but still the risk of coronary artery disease remains. The initial approach for reducing lipid contents in diabetic patients should include glycemic control, diet, weight loss, and exercise. But if it fails then lipid-lowering agents like fibrate and HMG CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors should work effectively. In the present study results of atorvastatin compared with biguanides proved atorvastatin as a more effective lipid-lowering agent along with antidiabetic activity so it can effectively help in reducing the risk of cardiovascular disease (CVD.

  10. Modern approach to metabolic rehabilitation of cancer patients: biguanides (phenformin and metformin) and beyond.

    Science.gov (United States)

    Berstein, Lev M

    2010-08-01

    Comparing the experience accumulated for more than 40 years in the Laboratory of Endocrinology of Petrov Institute of Oncology (St Petersburg, Russia) with similar approaches practiced elsewhere, evidence supports the reasonability of metabolic rehabilitation of patients suffering from breast cancer or other hormone-dependent malignancies. The primary objective of such approaches is to improve treatment results by ameliorating hormonal-metabolic disturbances, including excess body fat, glucose intolerance, insulin resistance and manifestations of endocrine-genotoxic switchings, and modify tissue and cellular targets or mechanisms related or nondirectly related to the aforementioned disturbances. The relevant measures may be categorized as pharmacological (antidiabetic biguanides exemplified with metformin being most popular but not exclusive) and nonpharmacological (rational nutrition, moderate physical activity and so forth) and used separately or in different combinations.

  11. Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment.

    Science.gov (United States)

    Narise, Kosuke; Okuda, Kensuke; Enomoto, Yukihiro; Hirayama, Tasuku; Nagasawa, Hideko

    2014-01-01

    Adaptive cellular responses resulting from multiple microenvironmental stresses, such as hypoxia and nutrient deprivation, are potential novel drug targets for cancer treatment. Accordingly, we focused on developing anticancer agents targeting the tumor microenvironment (TME). In this study, to search for selective antitumor agents blocking adaptive responses in the TME, thirteen new compounds, designed and synthesized on the basis of the arylmethylbiguanide scaffold of phenformin, were used in structure activity relationship studies of inhibition of hypoxia inducible factor (HIF)-1 and unfolded protein response (UPR) activation and of selective cytotoxicity under glucose-deprived stress conditions, using HT29 cells. We conducted luciferase reporter assays using stable cell lines expressing either an HIF-1-responsive reporter gene or a glucose-regulated protein 78 promoter-reporter gene, which were induced by hypoxia and glucose deprivation stress, respectively, to screen for TME-targeting antitumor drugs. The guanidine analog (compound 2), obtained by bioisosteric replacement of the biguanide group, had activities comparable with those of phenformin (compound 1). Introduction of various substituents on the phenyl ring significantly affected the activities. In particular, the o-methylphenyl analog compound 7 and the o-chlorophenyl analog compound 12 showed considerably more potent inhibitory effects on HIF-1 and UPR activation than did phenformin, and excellent selective cytotoxicity under glucose deprivation. These compounds, therefore, represent an improvement over phenformin. They also suppressed HIF-1- and UPR-related protein expression and secretion of vascular endothelial growth factor-A. Moreover, these compounds exhibited significant antiangiogenic effects in the chick chorioallantoic membrane assay. Our structural development studies of biguanide derivatives provided promising candidates for a novel anticancer agent targeting the TME for selective cancer

  12. Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity during glucose deprivation.

    Science.gov (United States)

    Matsuo, Junichi; Tsukumo, Yoshinori; Saito, Sakae; Tsukahara, Satomi; Sakurai, Junko; Sato, Shigeo; Kondo, Hiromichi; Ushijima, Masaru; Matsuura, Masaaki; Watanabe, Toshiki; Tomida, Akihiro

    2012-05-01

    Biguanides, including metformin, buformin, and phenformin, are potential antitumorigenic agents and induce cell death during glucose deprivation, a cell condition that occurs in the tumor microenvironment. Here, we show that this selective killing of glucose-deprived cells is coupled with hyperactivation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator of translation initiation. We found, in fact, that the 4E-BP1 hyperactivation led to failure of the unfolded protein response (UPR), an endoplasmic reticulum-originated stress signaling pathway for cell survival. We also found that the 4E-BP1-mediated UPR inhibition occurred through a strong inhibition of the mTOR signaling pathway, a proven antitumor target. Importantly, the 4E-BP1 hyperactivation can be also seen in xenografted cancer cells through an in vivo biguanide treatment. Our findings indicate that antitumor action of biguanides can be mediated by 4E-BP1 hyperactivation, which results in UPR inhibition and selective cell killing when glucose is withdrawn.

  13. Study of epigenetic properties of Poly(HexaMethylene Biguanide) hydrochloride (PHMB).

    Science.gov (United States)

    Creppy, Edmond E; Diallo, Aboudoulatif; Moukha, Serge; Eklu-Gadegbeku, Christophe; Cros, Daniel

    2014-08-08

    Poly(HexaMethylene Biguanide) hydrochloride (PHMB) CAS No. [32289-58-0] is a particularly effective member of the biguanides antiseptic chemical group, and has been in use since the early fifties in numerous applications. It has been proposed that PHMB be classified as a category 3 carcinogen although PHMB is not genotoxic. It has been hypothesized that PHMB may have epigenetic properties effects, including non-genotoxic modifications of DNA bases, DNA methylation and mitogenic cytokine production. These properties have been assessed in vitro using 3 cell types: Caco-2 cells (from a human colon adenocarcinoma) with a non-functional p53 gene. (∆p53: mut p53), N2-A (Neuro-2A cells, mouse neural cells), the brain being a possible target organ in rodents and HepG2 cells (human hepatocellular carcinoma) with functional p53 gene. From the concentration 1 µg/mL up to 20 µg/mL of PHMB, no effect was observed, either growth stimulation or inhibition. Viability testing using neutral red led to an IC 50 of 20-25 µg/mL after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80 µg/mL, 160 µg/mL and 160 µg/mL respectively for HepG2 cells, Neuro-2A cells and Caco-2 cells. PHMB does not induce significant oxidative stress (production of MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG) and/or its hypermethylation (m5dC), the latter being strongly implicated in DNA replication and regulation and cell division. PHMB does not induce significant production of mitogenic cytokines such as TNF-α (tumor necrosis factor), interleukins (IL-1 alpha), and the transcription factor nuclear factor kappa B (NF-κB) which can cause either apoptosis or stimulate the growth of transformed cells or tumors. Instead, from concentrations of 20 to 100 µg/mL, PHMB kills cells of all types in less than 3 h. The expression of genes involved in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic gene bax and others, the anti

  14. Understanding the biocide action of poly(hexamethylene biguanide) using Langmuir monolayers of dipalmitoyl phosphatidylglycerol.

    Science.gov (United States)

    Souza, Adriano L; Ceridório, Lucinéia F; Paula, Gustavo F; Mattoso, Luiz H C; Oliveira, Osvaldo N

    2015-08-01

    The disinfectant activity of poly(hexamethylene biguanide) (PHMB) has been explored in industrial applications, in agriculture and in food manipulation, but this biocide action is not completely understood. It is believed to arise from electrostatic interactions between the polyhexanide group and phosphatidylglycerol, which is the main phospholipid on the bacterial membrane. In this study, we investigated the molecular-level interactions between PHMB and dipalmitoyl phosphatidylglycerol (DPPG) in Langmuir monolayers that served as cell membrane models. PHMB at a concentration of 2×10(-4) g L(-1) in a Theorell-Stenhagen at pH 3.0 and in a phosphate at pH 7.4 was used as a subphase to prepare the DPPG monolayers. Surface pressure-area isotherms showed that PHMB adsorbs and penetrates into the DPPG monolayers, expanding them and increasing their elasticity under both conditions examined. Results from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) indicated that PHMB induces disorder in the DPPG chains and dehydrates their C=O groups, especially for the physiological medium. Overall, these findings point to hydrophobic interactions and dehydration being as relevant as electrostatic interactions to explain changes in membrane fluidity and permeability, believed to be responsible for the biocide action of PHMB.

  15. Effects of Polyhexamethylene Biguanide and Polyquaternium-1 on Phospholipid Bilayer Structure and Dynamics.

    Science.gov (United States)

    Horner, Ian J; Kraut, Nadine D; Hurst, Jerod J; Rook, Alyssa M; Collado, Crystal M; Atilla-Gokcumen, G Ekin; Maziarz, E Peter; Liu, X Michael; Merchea, Mohinder M; Bright, Frank V

    2015-08-20

    Multipurpose solutions (MPS) are a single solution that functions to simultaneously rinse, disinfect, clean, and store soft contact lenses. Several commercial MPS products contain polyhexamethylene biguanide (PHMB) and/or polyquaternium-1 (PQ-1) as antimicrobial agents. In this paper we have created an in vitro small unilamellar vesicle (SUV) model of the corneal epithelial surface, and we have assessed the interactions of PHMB and PQ-1 with several model biomembranes by using fluorescence spectroscopy, dynamic light scattering (DLS), and liquid chromatography-mass spectrometry (LC-MS). Steady-state and time-resolved fluorescence were used to assess the membrane acyl chain and polar headgroup region local microenvironment as a function of added PHMB or PQ-1. DLS was used to detect and quantify SUV aggregation induced by PHMB and PQ-1. LC-MS was used to determine the liposomal composition from any precipitated materials in comparison to the as-prepared SUVs. The results are consistent with PHMB adsorbing onto and PQ-1 intercalating into the biomembrane structure. The differences between the two interaction mechanisms have substantial impacts on the biomembrane dynamics and stability.

  16. In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin

    Science.gov (United States)

    Laustriat, Delphine; Gide, Jacqueline; Barrault, Laetitia; Chautard, Emilie; Benoit, Clara; Auboeuf, Didier; Boland, Anne; Battail, Christophe; Artiguenave, François; Deleuze, Jean-François; Bénit, Paule; Rustin, Pierre; Franc, Sylvia; Charpentier, Guillaume; Furling, Denis; Bassez, Guillaume; Nissan, Xavier; Martinat, Cécile; Peschanski, Marc; Baghdoyan, Sandrine

    2015-01-01

    Major physiological changes are governed by alternative splicing of RNA, and its misregulation may lead to specific diseases. With the use of a genome-wide approach, we show here that this splicing step can be modified by medication and demonstrate the effects of the biguanide metformin, on alternative splicing. The mechanism of action involves AMPK activation and downregulation of the RBM3 RNA-binding protein. The effects of metformin treatment were tested on myotonic dystrophy type I (DM1), a multisystemic disease considered to be a spliceopathy. We show that this drug promotes a corrective effect on several splicing defects associated with DM1 in derivatives of human embryonic stem cells carrying the causal mutation of DM1 as well as in primary myoblasts derived from patients. The biological effects of metformin were shown to be compatible with typical therapeutic dosages in a clinical investigation involving diabetic patients. The drug appears to act as a modifier of alternative splicing of a subset of genes and may therefore have novel therapeutic potential for many more diseases besides those directly linked to defective alternative splicing. PMID:26528939

  17. Opinion of the scientific committee on consumer safety (SCCS)--2nd Revision of the safety of the use of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products.

    Science.gov (United States)

    Bernauer, Ulrike

    2015-12-01

    Conclusion of the opinion: On the basis of the data available, the SCCS concludes that Polyaminopropyl Biguanide (PHMB) is not safe for consumers when used as a preservative in cosmetic spray formulations and in all cosmetic products up to the maximum concentration of 0.3%. The safe use could be based on a lower use concentration and/or restrictions with regard to cosmetic products' categories. Dermal absorption studies on additional representative cosmetic formulations are needed. PHMB is used in a variety of applications other than cosmetics. General exposure data from sources others than cosmetics should be submitted for the assessment of the aggregate exposure of PHMB.

  18. A systems pharmacokinetic and pharmacodynamic approach to identify opportunities and pitfalls in energy stress-mediated chemoprevention: the use of metformin and other biguanides.

    Science.gov (United States)

    Thompson, Matthew D; Thompson, Henry J

    2012-12-01

    Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin.

  19. Study of Epigenetic Properties of Poly(HexaMethylene Biguanide Hydrochloride (PHMB

    Directory of Open Access Journals (Sweden)

    Edmond E. Creppy

    2014-08-01

    Full Text Available Poly(HexaMethylene Biguanide hydrochloride (PHMB CAS No. [32289-58-0] is a particularly effective member of the biguanides antiseptic chemical group, and has been in use since the early fifties in numerous applications. It has been proposed that PHMB be classified as a category 3 carcinogen although PHMB is not genotoxic. It has been hypothesized that PHMB may have epigenetic properties effects, including non-genotoxic modifications of DNA bases, DNA methylation and mitogenic cytokine production. These properties have been assessed in vitro using 3 cell types: Caco-2 cells (from a human colon adenocarcinoma with a non-functional p53 gene. (∆p53: mut p53, N2-A (Neuro-2A cells, mouse neural cells, the brain being a possible target organ in rodents and HepG2 cells (human hepatocellular carcinoma with functional p53 gene. From the concentration 1 µg/mL up to 20 µg/mL of PHMB, no effect was observed, either growth stimulation or inhibition. Viability testing using neutral red led to an IC 50 of 20–25 µg/mL after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80 µg/mL, 160 µg/mL and 160 µg/mL respectively for HepG2 cells, Neuro-2A cells and Caco-2 cells. PHMB does not induce significant oxidative stress (production of MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG and/or its hypermethylation (m5dC, the latter being strongly implicated in DNA replication and regulation and cell division. PHMB does not induce significant production of mitogenic cytokines such as TNF-α (tumor necrosis factor, interleukins (IL-1 alpha, and the transcription factor nuclear factor kappa B (NF-κB which can cause either apoptosis or stimulate the growth of transformed cells or tumors. Instead, from concentrations of 20 to 100 µg/mL, PHMB kills cells of all types in less than 3 h. The expression of genes involved in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic gene bax and others

  20. Organic salts of biguanide - An attempt to crystal engineering of novel materials for second harmonic generation

    Science.gov (United States)

    Matulková, Irena; Němec, Ivan; Císařová, Ivana; Němec, Petr; Vaněk, Přemysl

    2010-03-01

    Three organic salts of biguanide with oxalic, succinic and L-tartaric acids have been prepared and X-ray structural analysis has been performed. Biguanidium(1+) oxalate hemihydrate ( a = 6.8330(2) Å, b = 10.0430(2) Å, c = 14.6230(4) Å, α = 90.236(1) , β = 90.333(1) , γ = 105.605(2) , V = 966.46(4) Å 3, Z = 1, R = 0.0393 for 3704 observed reflections) and biguanidium(1+) hydrogen succinate ( a = 6.4600(1) Å, b = 6.7670(2) Å, c = 11.4150(3) Å, α = 91.822(1) , β = 105.312(1) , γ = 90.922(1) , V = 480.89(2) Å 3, Z = 2, R = 0.0357 for 1880 observed reflections) belong to the triclinic space group P 1¯. Their crystal structures are based on biguanidium(1+) pairs connected by intermolecular N-H⋯N hydrogen bonds. The remaining ions (eventually water molecules) form a 3D structural network with these pairs. Furthermore, the formation of the cationic and anionic layers interconnected by intermolecular N-H⋯O hydrogen bonds was observed in the crystal structure of biguanidium(1+) hydrogen succinate. Biguanidium(2+) L-tartrate crystallizes in the orthorhombic space group P 2 12 12 1 ( a = 6.7170(2) Å, b = 9.2740(2) Å, c = 16.1500(4) Å, V = 1006.04(4) Å 3, Z = 4, R = 0.0432 for 2193 observed reflections). The crystal structure is based on L-tartrate chains, which are interconnected by isolated biguanidium(2+) cations via several types of N-H⋯O hydrogen bonds. The formation of L-tartrate chains is mediated by two types of intermolecular O-H⋯O hydrogen bonds connecting the hydroxyl and carboxylate groups. The FTIR and FT Raman spectra of all the compounds were recorded and discussed. The theoretical values of the first hyperpolarizability components were calculated for biguanidium(1+) and biguanidium(2+) cations at the B3LYP level with the 6-311G(d,p) basis set. Quantitative measurements of the second harmonic generation of powdered biguanidium(2+) L-tartrate at 800 nm were performed and a relative efficiency of 2% (compared to KDP) was

  1. Cu(II AND Zn(II COMPLEX COMPOUNDS WITH BIGUANIDES AROMATIC DERIVATIVES. SYNTHESIS, CHARACTERIZATION, BIOLOGICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Ticuţa Negreanu-Pîrjol

    2011-05-01

    Full Text Available In this paper we report the synthesis, physical-chemical characterization and antimicrobial activity of some new complex compounds of hetero-aromatic biguanides ligands, chlorhexidine base (CHX and chlorhexidine diacetate (CHXac2 with metallic ions Cu(II and Zn(II, in different molar ratio. The synthesized complexes were characterized by elemental chemical analysis and differential thermal analysis. The stereochemistry of the metallic ions was determined by infrared spectra, UV-Vis, EPR spectroscopy and magnetic susceptibility in the aim to establish the complexes structures. The biological activity of the new complex compounds was identified in solid technique by measuring minimum inhibition diameter of bacterial and fungal culture, against three standard pathogen strains, Escherichia coli ATCC 25922, Staphilococcus aureus ATCC 25923 and Candida albicans ATCC 10231. The results show an increased specific antimicrobial activity for the complexes chlorhexidine:Cu(II 1:1 and 1:2 compared with the one of the Zn(II complexes.

  2. Determination of metformin and other biguanides in forensic whole blood samples by hydrophilic interaction liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Sørensen, Lambert K

    2012-01-01

    Metformin is an anti-diabetic drug in the biguanide class which also includes phenformin and buformin. Because of the potential adverse effects of the biguanides, a reliable liquid chromatography-tandem mass spectrometry method using pneumatically assisted electrospray ionization was developed for the quantification of the drugs in both live and post-mortem human whole blood. The blood proteins were precipitated by the addition of a mixture of methanol and acetonitrile, and the extract was cleaned up by cation-exchange solid-phase extraction to eliminate ion suppression effects. The separation was performed by hydrophilic interaction liquid chromatography. Matrix-matched calibrants combined with isotope dilution of metformin were used for calibration. The detection limits were 0.01 mg/L for metformin and phenformin and the relative intra-laboratory reproducibility standard deviations were less than 6% at concentrations of 1-10 mg/L. The mean true recoveries were greater than 86%.

  3. Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention

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    Hiromi Sanada

    2014-04-01

    Full Text Available Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings.

  4. A new non-invasive approach based on polyhexamethylene biguanide increases the regression rate of HPV infection

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    Gentile Antonio

    2012-09-01

    Full Text Available Abstract Background HPV infection is a worldwide problem strictly linked to the development of cervical cancer. Persistence of the infection is one of the main factors responsible for the invasive progression and women diagnosed with intraepithelial squamous lesions are referred for further assessment and surgical treatments which are prone to complications. Despite this, there are several reports on the spontaneous regression of the infection. This study was carried out to evaluate the effectiveness of a long term polyhexamethylene biguanide (PHMB-based local treatment in improving the viral clearance, reducing the time exposure to the infection and avoiding the complications associated with the invasive treatments currently available. Method 100 women diagnosed with HPV infection were randomly assigned to receive six months of treatment with a PHMB-based gynecological solution (Monogin®, Lo.Li. Pharma, Rome - Italy or to remain untreated for the same period of time. Results A greater number of patients, who received the treatment were cleared of the infection at the two time points of the study (three and six months compared to that of the control group. A significant difference in the regression rate (90% Monogin group vs 70% control group was observed at the end of the study highlighting the time-dependent ability of PHMB to interact with the infection progression. Conclusions The topic treatment with PHMB is a preliminary safe and promising approach for patients with detected HPV infection increasing the chance of clearance and avoiding the use of invasive treatments when not strictly necessary. Trial registration ClinicalTrials.gov Identifier NCT01571141

  5. The phenanthridine biguanides efficiently differentiate between dGdC, dAdT and rArU sequences by two independent, sensitive spectroscopic methods.

    Science.gov (United States)

    Radić Stojković, Marijana; Miljanić, Snežana; Mišković, Katarina; Glavaš-Obrovac, Ljubica; Piantanida, Ivo

    2011-05-01

    At submicromolar concentrations two novel phenanthridine biguanides exhibit distinctly different spectroscopic signals for dGdC and dAdT sequences, respectively, by opposite fluorimetric changes (quenching for dGdC and increase for dAdT) and especially the bis-biguanide derivative gives an opposite ICD response (negative ICD for dGC and strong positive for dAdT). This specific signalling was explained by the ability of compounds to switch the binding mode from intercalation into dGdC to minor groove binding into dAdT sequences. Both compounds bind to rArU by intercalation, yielding different fluorimetric and CD response in comparison to any of aforementioned ds-DNA. Moreover, both compounds revealed significantly higher affinity toward ds-polynucleotides in comparison to previously studied alkylamine- and urea-analogues. Furthermore, DNA/RNA binding properties of novel compounds could be controlled by pH, due to the protonation of heterocyclic nitrogen. Low in vitro cytotoxicity of both compounds against human cell lines makes them interesting spectrophotometric probes.

  6. The effect of the disulfideisomerase domain containing protein in the defense against polyhexamethylene biguanide of highly tolerant Acanthamoeba at the trophozoite stage

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    Fu-Chin Huang

    2016-12-01

    Full Text Available Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB over a period of several days but this is not entirely effective against all strains/isolates. The tolerance mechanisms of PHMB in Acanthamoeba cells remain unclear. In this study, we found that the mRNA expression level of disulfideisomerase domain containing protein (PDI increased rapidly in surviving cells of the highly PHMB-tolerant Acanthamoeba castellanii strain, NCKH_D, during PHMB treatment, but not in the ATCC standard strain. After PDI-specific silencing, NCKH_D was found to be more vulnerable to PHMB treatment. The results described above show that PDI is an important gene for PHMB tolerance ability in a highly PHMB-tolerant strain of Acanthamoeba and provide a new insight for more efficient medicine development for Acanthamoeba keratitis.

  7. Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study)

    DEFF Research Database (Denmark)

    Anholm, Christian; Kumarathurai, Preman; Klit, Malene S;

    2014-01-01

    INTRODUCTION: Newly diagnosed type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD) more than doubles the risk of death compared with otherwise matched glucose tolerant patients. The biguanide metformin is the drug of choice in treatment of T2DM and has shown to ameliorate......), liraglutide, is currently used for treatment of T2DM but its potential effect on cardiac function has not been investigated in detail. We hypothesised that liraglutide added to metformin backbone therapy in patients with CAD and newly diagnosed T2DM will improve β-cell function and left ventricular systolic...... function during dobutamine stress. METHODS AND ANALYSES: 40 patients with CAD and newly diagnosed T2DM will receive the intervention liraglutide+metformin and placebo+metformin in this investigator-initiated, double blind, randomised, placebo-controlled, cross-over 12 plus 12 weeks intervention study...

  8. Assessment of the mode of action of polyhexamethylene biguanide against Listeria innocua by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis.

    Science.gov (United States)

    Chadeau, Elise; Dumas, Emilie; Adt, Isabelle; Degraeve, Pascal; Noël, Claude; Girodet, Christophe; Oulahal, Nadia

    2012-12-01

    Polyhexamethylene biguanide (PHMB) is a cationic biocide. The antibacterial mode of action of PHMB (at concentrations not exceeding its minimal inhibitory concentration) upon Listeria innocua LRGIA 01 was investigated by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis. Fourier transformed infrared spectra of bacteria treated with or without PHMB presented some differences in the lipids region: the CH(2)/CH(3) (2924 cm(-1)/2960 cm(-1)) band areas ratio significantly increased in the presence of PHMB. Since this ratio generally reflects membrane phospholipids and membrane microenvironment of the cells, these results suggest that PHMB molecules interact with membrane phospholipids and, thus, affect membrane fluidity and conformation. To assess the hypothesis of PHMB interaction with L. innocua membrane phospholipids and to clarify the PHMB mode of action, we performed fluorescence anisotropy experiments. Two probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its derivative 1-[4-(trimethyl-amino)-phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), were used. DPH and TMA-DPH incorporate inside and at the surface of the cytoplasmic membrane, respectively. When PHMB was added, an increase of TMA-DPH fluorescence anisotropy was observed, but no changes of DPH fluorescence anisotropy occurred. These results are consistent with the hypothesis that PHMB molecules perturb L. innocua LRGIA 01 cytoplasmic membrane by interacting with the first layer of the membrane lipid bilayer.

  9. Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.

    Science.gov (United States)

    Granja, Sara; Marchiq, Ibtissam; Le Floch, Renaud; Moura, Conceição Souto; Baltazar, Fátima; Pouysségur, Jacques

    2015-03-30

    Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via 'Zinc-Finger Nucleases'. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin.

  10. Rapid, simple and stability-indicating determination of polyhexamethylene biguanide in liquid and gel-like dosage forms by liquid chromatography with diode-array detection

    Institute of Scientific and Technical Information of China (English)

    Markus Küsters; Sören Beyer; Stephan Kutscher; Harald Schlesinger; Michael Gerhartz

    2013-01-01

    A rapid and simple method for the determination of polyhexamethylene biguanide (polyhexanide, PHMB) in liquid and gel-like pharmaceutical formulations by means of high performance liquid chromatography coupled to diode-array detection (HPLC-DAD) was developed. Best separation was achieved using a cyanopropyl bonded phase (Agilent Zorbax Eclipse XDB-CN column 4.6 mm75 mm with particle size of 3.5 mm) as well as gradient elution consisting of acetonitrile/deionized water at a flow rate of 1.0 mL/min. The optimized and applied chromatographic conditions permitted separation of polyhexanide from interacting matrix with subsequent detection at a wavelength of 235 nm with good sensitivity. The method validation was carried out with regard to the guidelines for analytical procedures demanded by the International Conference on Harmonisation (ICH). Mean recoveries of 102% and 101% for gel-like as well as liquid preparations were obtained. Suitable repeatability as well as intermediate precision could be achieved with limits of detection r0.004 mg/mL for both formulations, equivalent to r0.004% PHMB concerning sample preparation. Determination of PHMB was accomplished without tedious sample preparation. Interacting matrix could be eliminated by the chromatographic procedure with excellent performance of system suitability. All analytical requirements were fulfilled permitting a reliable and precise determination of PHMB in pharmaceuticals. Furthermore, the developed method was applied to stability testing of pharmaceutical preparations containing PHMB.

  11. The safety and efficacy of bacterial nanocellulose wound dressing incorporating sericin and polyhexamethylene biguanide: in vitro, in vivo and clinical studies.

    Science.gov (United States)

    Napavichayanun, Supamas; Yamdech, Rungnapha; Aramwit, Pornanong

    2016-03-01

    In our previous work, we have attempted to develop a novel bacterial nanocellulose wound dressing which composed of both polyhexamethylene biguanide (PHMB) as an antimicrobial agent and sericin as an accelerative wound healing component. The loading sequence and concentration of PHMB and sericin were optimized to provide the wound dressing with the most effective antimicrobial activity and enhanced collagen production. In this study, further in vitro, in vivo, and clinical studies of this novel wound dressing were performed to evaluate its safety, efficacy, and applicability. For the in vitro cytotoxic test with L929 mouse fibroblast cells, our novel dressing was not toxic to the cells and also promoted cell migration as good as the commercially available dressing, possibly due to the component of sericin released. When implanted subcutaneously in rats, the lower inflammation response was observed for the novel dressing implanted, comparing to the commercially available dressing. This might be that the antimicrobial PHMB component of the novel dressing played a role to reduce infection and inflammation reaction. The clinical trial patch test was performed on the normal skin of healthy volunteers to evaluate the irritation effect of the dressing. Our novel dressing did not irritate the skin of any volunteers, as characterized by the normal levels of erythema and melanin and the absence of edema, papule, vesicle, and bullae. Then, the novel dressing was applied for the treatment of full-thickness wounds in rats. The wounds treated with our novel dressing showed significantly lower percentage of wound size and higher extent of collagen formation mainly due to the activity of sericin. We concluded that our novel bacterial nanocellulose incorporating PHMB and sericin was a safe and efficient wound dressing material for further investigation in the wound healing efficacy in clinic.

  12. The resistance of the yeast Saccharomyces cerevisiae to the biocide polyhexamethylene biguanide: involvement of cell wall integrity pathway and emerging role for YAP1

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    de Morais Marcos A

    2011-08-01

    Full Text Available Abstract Background Polyhexamethylene biguanide (PHMB is an antiseptic polymer that is mainly used for cleaning hospitals and pools and combating Acantamoeba infection. Its fungicide activity was recently shown by its lethal effect on yeasts that contaminate the industrial ethanol process, and on the PE-2 strain of Saccharomyces cerevisiae, one of the main fermenting yeasts in Brazil. This pointed to the need to know the molecular mechanism that lay behind the cell resistance to this compound. In this study, we examined the factors involved in PHMB-cell interaction and the mechanisms that respond to the damage caused by this interaction. To achieve this, two research strategies were employed: the expression of some genes by RT-qPCR and the analysis of mutant strains. Results Cell Wall integrity (CWI genes were induced in the PHMB-resistant Saccharomyces cerevisiae strain JP-1, although they are poorly expressed in the PHMB-sensitive Saccharomyces cerevisiae PE2 strain. This suggested that PHMB damages the glucan structure on the yeast cell wall. It was also confirmed by the observed sensitivity of the yeast deletion strains, Δslg1, Δrom2, Δmkk2, Δslt2, Δknr4, Δswi4 and Δswi4, which showed that the protein kinase C (PKC regulatory mechanism is involved in the response and resistance to PHMB. The sensitivity of the Δhog1 mutant was also observed. Furthermore, the cytotoxicity assay and gene expression analysis showed that the part played by YAP1 and CTT1 genes in cell resistance to PHMB is unrelated to oxidative stress response. Thus, we suggested that Yap1p can play a role in cell wall maintenance by controlling the expression of the CWI genes. Conclusion The PHMB treatment of the yeast cells activates the PKC1/Slt2 (CWI pathway. In addition, it is suggested that HOG1 and YAP1 can play a role in the regulation of CWI genes.

  13. Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.

    Science.gov (United States)

    Bard, J M; Charles, M A; Juhan-Vague, I; Vague, P; André, P; Safar, M; Fruchart, J C; Eschwege, E

    2001-03-01

    The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (>/=0.95 for men and >/=0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides >/=1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels

  14. STUDY ON DISINFECTION RELATED PROPERTIES OF A COMPOUND POLY HEXAMETHYLENE BIGUANIDE HYDROCHLORIDE DISINFECTANT%一种复方聚六亚甲基盐酸双胍消毒液消毒相关性能研究

    Institute of Scientific and Technical Information of China (English)

    刘仲霞; 陆武韬; 苏伟东

    2011-01-01

    Objective To study the disinfection related properties of a poly hexamethylene biguanide hydrochloride disinfectant. Methods Suspensionr quantitative germicidal test and animal toxic experiment were used to observe the germicidal efficacy and the toxicity of the compound disinfectant in laboratory. Results The killing logarithm values of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa by the disinfectant solution containing poly hexamethylene biguanide hydrochloride 146 mg/L with 7.5 min contact time were all above 5.00. The killing logarithm value of Candida albicans and by the disinfectant solution containing poly hexamethylene biguanide hydrochloride 146 mg/L with 22.5 min contact time was 2.07. The LD50 of mice acute oral toxicity was > 5 000 mg/kg · bw. The disinfectant has slightly - irritating to rabbit eye and mucosa and has medium irritating to rabbit skin. The result of mouse bone marrow polychromatic erythrocyte micronucleus test was negative. Conclusions The compound poly hexamethylene biguanide hydrochloride disinfectant had good germicidal efficacy to vegetative forms of bacteria. It was low toxicity and has slightly - irritating to rabbit eye and skin.%目的 研究一种复方聚六亚甲基胍盐酸盐消毒液消毒相关性能.方法 采用悬液定量杀菌试验和动物毒性试验的方法,对该复方消毒液杀菌效果及其毒性进行了实验室观察.结果 用含聚六亚甲基盐酸双胍146 mg/L的该消毒液分别对悬液中的大肠杆菌、金黄色葡萄球菌、白色葡萄球菌及铜绿假单胞菌作用7.5 min,杀灭对数值均>5.00.用聚六亚甲基盐酸双胍146 mg/L的该复方消毒液对悬液内白色念珠菌作用22.5 min,杀灭对数值为2.07.该复方聚六亚甲基盐酸双胍消毒液对小鼠急性经口LD50值>5 000 mg/kg(体重);该消毒液原液对家兔眼睛黏膜和完整皮肤有轻刺激性和中等刺激性;该消毒液对小鼠骨髓嗜多染红细

  15. Determination of antihyperglycemic biguanides in serum and urine using an ion-pair solid-phase extraction technique followed by HPLC-UV on a pentafluorophenylpropyl column and on an octadecyl column.

    Science.gov (United States)

    Tahara, Kayoko; Yonemoto, Ayumi; Yoshiyama, Yuji; Nakamura, Toshiya; Aizawa, Masaaki; Fujita, Yoshikuni; Nishikawa, Takashi

    2006-11-01

    An HPLC-UV method was established for the determination of metformin and buformin in biological fluids. Metformin was not retained on particles packed in conventional solid-phase extraction cartridges; in contrast, buformin was retained too firmly and not eluted with a solvent for recovery. However, both drugs were retained on particles that had been treated with an ion-pair reagent of heptanesulfonate or dodecylsulfate and recovered almost completely. The recovered fraction was subjected to HPLC on a pentafluorophenylpropyl column which was suitable for the determination of both biguanides in serum and in urine. Limits of quantitation were low enough for clinical use, and reproducibility was high with an RSD of 0.9-2.3%. HPLC on a conventional octadecyl column was suitable only for the determination of buformin in serum since interfering peaks appeared on the chromatograms of urine samples. The method was applied to analysis of some clinical specimens.

  16. NCW2, a Gene Involved in the Tolerance to Polyhexamethylene Biguanide (PHMB), May Help in the Organisation of β-1,3-Glucan Structure of Saccharomyces cerevisiae Cell Wall.

    Science.gov (United States)

    Elsztein, Carolina; de Lima, Rita de Cássia Pereira; de Barros Pita, Will; de Morais, Marcos Antonio

    2016-09-01

    In the present work, we provide biological evidences supporting the participation of NCW2 gene in the mechanism responsible for cell tolerance to polyhexamethylene biguanide (PHMB), an antifungal agent. The growth rate of yeast cells exposed to this agent was significantly reduced in ∆ncw2 strain and the mRNA levels of NCW2 gene in the presence of PHMB showed a 7-fold up-regulation. Moreover, lack of NCW2 gene turns yeast cell more resistant to zymolyase treatment, indicating that alterations in the β-glucan network do occur when Ncw2p is absent. Computational analysis of the translated protein indicated neither catalytic nor transmembrane sites and reinforced the hypothesis of secretion and anchoring to cell surface. Altogether, these results indicated that NCW2 gene codes for a protein which participates in the cell wall biogenesis in yeasts and that Ncw2p might play a role in the organisation of the β-glucan assembly.

  17. Cooperativity in the Binding of the Cationic Biocide Polyhexamethylene Biguanide to Nucleic Acids%阳离子型抗菌剂聚六亚甲基双胍与核酸结合的协同作用

    Institute of Scientific and Technical Information of China (English)

    Michael J. Allen; Andrew P. Morby; Graham F. White; 江正武; 赵春霞; 刘白玲

    2011-01-01

    研究了广谱抗菌剂聚六亚甲基双胍(PHMB)与各类核酸的相互作用。通过滴定反应研究了PHMB与具有100个碱基(对)的单(双)链DNA、混合长度的标准DNA、tRNA相互作用形成的复合物沉淀。试验发现:PHMB与核酸之间是核苷酸/双胍基团以单元比相结合的。它们之间的这种结合具有很强的协同性,其表观Hill系数为10.3—14.6。用核酸滴定PHMB的荧光衍生物时,四类核酸的作用都显示了很强的荧光偏振强度,表明了核酸与PHMB之间的结合作用。PHMB与各类核酸之间强烈而广泛的结合作用.对这类抗菌剂的作用机理有%The interaction between the broad - spectrum antimicrobial agent, polyhexamethylene biguanide ( PHMB), and various nucleic acids was investigated. Titration of either single - or double - stranded 100 - bp DNA, or mixed - molecular weight marker DNA, or tRNA with PHMB caused precipitation of a complex between nucleic acid and PHMB in which the nucleotide/ biguanide ratio was always close to unity. Binding of PHMB was highly cooperative, with apparent Hill coefficients I0.3 - 14.6. When a fluorescent derivative of PHMB was titrated with increasing amounts of nucleic acid, all four forms of nucleic acid caused strong polarisation of fluorescence, demonstrating the association with PHMB. The intensity and broad - spectrum binding of PHMB to all forms of nucleic acid has significant implications for the mechanism of action of this biocide.

  18. Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates.

    Science.gov (United States)

    Umehara, K-I; Iwatsubo, T; Noguchi, K; Kamimura, H

    2007-06-01

    In this study, the comparison of the transport of substrates (1-methyl-4-phenylpydinium (MPP) and tetraethyl ammonium (TEA)) and the inhibition potency of the inhibitors (biguanides and H(2)-blockers) for human and rat organic cation transporters (hOCTs and rOcts), and the inhibition type of inhibitors for these transporters were investigated using HEK293 cells that stably express hOCT/rOct. The concentration-dependent uptake of [(3)H]-MPP and [(14)C]-TEA by hOCT1-3/rOct1-3 had K(m) values similar to those in the literature. It was also deduced that MPP and TEA are competitive inhibitors for hOCT1-2/rOct1-2. The K(i) values for phenformin inhibition of [(3)H]-MPP and [(14)C]-TEA uptake by hOCT1-3/rOct1-3 were lower than that for metformin. The [(3)H]-MPP uptake by hOCT1/rOct1 and hOCT3/rOct3 was inhibited by famotidine and ranitidine whereas that by hOCT2/rOct2 was not. The inhibitory potency of cimetidine for hOCT1-2 was very weak. In most cases, the differences in the V(max)/K(m) values of substrates and the K(i) values of inhibitors between hOCT and rOct were minor. The acquisition of information on OCT/Oct mediated-transport and/or inhibition such as that presented in this report is very useful for further understanding of certain aspects of uptake, distribution, and excretion for drug candidates.

  19. 消渴丸与双胍类降糖药治疗糖尿病疗效分析%Analysis of Xiaoke Pill and Biguanides Treatment Effect of Diabetes

    Institute of Scientific and Technical Information of China (English)

    赵有年; 马生渊

    2016-01-01

    目的:探讨消渴丸与双胍类降糖药物治疗糖尿病的临床疗效,以分析消渴丸是否具有临床实用价值。方法回顾性分析2014年9月-2015年9月期间在该院就诊的74例2型糖尿病患者,按照随机原则平均分为两组,其中对照组采用双胍类降糖药物二甲双胍治疗,而观察组患者采用消渴丸治疗,对比两组患者的治疗效果、治疗前后血糖、糖化血红蛋白(HbAlc)水平,并且根据统计观察组患者治疗前后的中医症状改善情况。结果对照组治疗后总有效率是75.68%(28/37),而观察组治疗后总有效率则是94.59%(35/37),差异有统计学意义(P<0.05);两组患者治疗后空腹血糖、餐后2h血糖以及HbAlc均有一定程度改善,其中以观察组患者改善程度更具优势,差异有统计学意义(P<0.05);观察组患者治疗后中医临床症状积分较治疗前有明显改善,差异有统计学意义(P<0.05)。结论对于2型糖尿病患者,采用消渴丸治疗能更好的稳定血糖,改善HbAlc水平,疗效也要明显优于双胍类降糖药,同时改善了患者中医临床症状,值得推广。%Objective To explore the clinical curative effect of Xiaoke pill and biguanide antidiabetic drug in the treatment of diabetic and to analyze whether Xiaoke pill has clinical practical value. Methods Retrospective analysis during Septem-ber September 2014 to 2015 in our hospital for treatment of 74 cases of type 2 diabetes patients, according to the principle of random average into two groups, the control group using biguanide antidiabetic drug metformin treatment, while the ob-servation group were treated with Xiaoke pill treatment and therapeutic effect were compared between the two groups of pa-tients, treatment before and after blood glucose, glycosylated hemoglobin (HbAlc) level, and according to statistics and ob-servation group before and after treatment in patients with TCM symptoms to improve the situation

  20. Determination of Biguanides in Anti-diabetic Health Foods by HPLC%HPLC法检测降血糖保健食品中的双胍类药物

    Institute of Scientific and Technical Information of China (English)

    王俊苏; 郗存显; 陈冬东; 张雷; 李贤良; 彭涛; 王国民

    2013-01-01

    OBJECTIVE: To establish the method for simultaneous determination of metformin and phenformin in anti-diabetic heath foods. METHODS: Metformin and phenformin were extracted from anti-diabetic heath foods ultrasonically with methanol-eth-anol(50:50, V/V), including anti-diabetic powder, milk powder, oral liquid, capsule and diabetes tea. The extraction liquid was cleaned up with WCX solid-phase extraction column, and determined by HPLC. Quantification was done by matrix-matched standard curve. RESULTS: The linear range of metformin and phenformin were 0.1-5.0 mg/L 0=0.999 9, r=0.999 5). Average recoveries of them were 91.9%-102.7% and 89.8%-107.0% , respectively (RSD<9.46%). The limits of quantification (LOQ) of them were 0.1 μg/g. None of metformin and phenformin was found in 5 samples. CONCLUSION: The method is simple, reliable and sensitive, which can be used to monitor biguanides in anti-diabetic health foods.%目的:建立同时检测降血糖保健食品中二甲双胍和苯乙双胍含量的方法.方法:采用甲醇-乙醇(50∶50,V/V)超声提取降血糖保健食品降糖粉、奶粉、口服液、胶囊、清渴茶中的二甲双胍和苯乙双胍,提取液经WCX固相萃取柱净化,高效液相色谱法测定,基质回收标准曲线定量.结果:二甲双胍和苯乙双胍检测质量浓度线性范围均为0.1~5.0 mg/L(r分别为0.999 9、0.999 5),回收率分别为91.9%~102.7%、89.8%~107.0%,RSD均低于9.46%,定量限均为0.1μg/g;5种试样中均未检出二甲双胍和苯乙双胍.结论:本方法简单、可靠、灵敏,可用于降血糖保健食品中双胍类药物的检测.

  1. 壳聚糖双胍盐酸盐络合碘制备及抑菌性能%Preparation and antibacterial properties of chitosan biguanide hydrochloride complex with iodine

    Institute of Scientific and Technical Information of China (English)

    徐宁宁; 谢琳琳; 唐阳; 赛明泽; 丁德润

    2015-01-01

    A novel derivative,chitosan biguanide hydrochloride (CGH),was synthesized by using chitosan (CTS) and dicyandiamide in a simple nucleophilic addition process at a certain temperature. Then,the complex compound (CGH-I2) was obtained by immersing CGH in iodine ethanol solution with different concentrations. The properties of CGH were characterized by means of IR,XRD,TG and DTG. The analysis of iodine content shows that the maximum mass ratio of CGH complex with iodine was m (CGH)∶m (I2) =1∶0. 46 when the concentration of iodine ethanol solution was 0.02mol/L. The antimicrobial test results show that the antibacterial diameters of the CGH-I2 against E. coli and Staphylococcus aureus were (18±1)mm and (21±1)mm respectively,with a high sensitivity of bacteriostasis.%以壳聚糖(CTS)和双氰胺为原料,在一定温度下通过亲核加成合成壳聚糖双胍盐酸盐(CGH)衍生物, CGH 与不同浓度的碘乙醇溶液制备改性壳聚糖的碘络合物(CGH-I2)。用 IR 光谱、XRD、TG 和 DTG 对衍生物进行表征,通过碘量法测 CGH 与碘络合的质量比。碘含量分析表明:碘乙醇溶液浓度为0.02mol/L 时,CGH 与碘络合的最大质量比为 m(CGH)∶m(I2)=1∶0.46。抑菌性测试表明:CGH-I2对大肠杆菌和金黄色葡萄球菌抑菌环直径分别为(18±1)mm 和(21±1)mm,敏感度均为高度敏感。

  2. ANTIBACTERIAL ACTIVITY AND QUANTIFICATION OF POLYHEXAMETHTYLENE BIGUANIDE HYDROCHLORIDE IN MUSCULAR TISSUES AND VISCERA OF BROILERS ATIVIDADE ANTIBACTERIANA E QUANTIFICAÇÃO DE CLORIDRATO DE POLIHEXAMETILENO BIGUANIDA (P.H.M.B. EM TECIDOS MUSCULARES E VÍCERAS DE FRANGOS

    Directory of Open Access Journals (Sweden)

    Albenones José de Mesquita

    2007-09-01

    Full Text Available

    Trials were carried out in order to check the viability of polyhexamethylene biguanide hydrochloride in the control of pathogenic and degenerating bacteria in carcass of chicken, as well as a spectrophotometric monitoring of the residual content of this polymer in the carcasses and viscera of chicken quenched with biguanide. The sanitizing power of this substance was high, although the previous analysis point out to the inefficacy of the residual monitoring method, due to the action of interferings.

    KEY-WORDS: Polyhexamethylene biguanide hydrochloride; carcass of chicken; sanitizer.

    Nos últimos anos, na procura de princípios sanitizantes ativos, certos polímeros sintéticos ou naturais modificados mereceram atenção especial por possuir uma ação antimicrobiana mais elevada, definida e por apresentar toxicidade reduzida, o que os tornam potencialmente úteis como sanitizantes nas indústrias alimentícias, onde se exigem condições higiênico-sanitárias satisfatórias. Nesta comunicação, foram ensaiados métodos para a viabilização do cloridrato de polihexametileno biguanida no controle de bactérias patogênicas ou deteriorantes em carcaças de frango, bem como um monitoramento espectrofotométrico do teor residual deste polímero nessas carcaças e vísceras de frangos dessedentados com biguanida. O poder sanitizante dessa substância foi elevado, no entanto as análises preliminares sugerem a ineficácia do método de monitoramento residual, devido à atuação de interferentes.

    PALAVRAS-CHAVE: Cloridrato de polihexametileno biguanida; carcaça de frango; sanitizante.

  3. Determination of biguanides in antidiabetic functional foods by LC-MS/MS%液相色谱-串联质谱测定降血糖功能食品中双胍类药物

    Institute of Scientific and Technical Information of China (English)

    王雅; 郗存显; 向露; 王俊苏; 陈冬东; 彭涛; 王国民; 母昭德

    2013-01-01

    ~ 8.4% and 1.1% ~10.3%,respectively.The method developed was simple,reliable and sensitive,which can be used to determine and identify the biguanides in antidiabetic functional foods.

  4. 胃肠道脂肪酶抑制剂联合双胍类降糖药对肥胖伴多囊不孕女性血清雌激素水平的影响%Effect of gastrointestinal lipase inhibitor combined with biguanides on serum estrogens in polycystic ovary syndrome with infertility

    Institute of Scientific and Technical Information of China (English)

    涂传发; 沈飞霞

    2016-01-01

    Objective To investigate the effect of gastrointestinal lipase inhibitor combined with biguanides on serum estrogens in the treatment of polycystic ovary syndrome with infertility in patients.Methods 72 cases with polycystic ovary syndrome with infertility from Huangyan Hospital Affiliated to Wenzhou Medical University were selected and randomly divided into 2 groups, 36 cases of each group.The control group received conventional therapy, and the treatment group received more with orlistat, serological indicators, clinical symptoms, signs, pregnancy rate and ovulation rate were compared after the treatment.Results Compared with control group, levels of blood glucose and blood lipid index decreased in treatment group after treatment (P<0.05), the levels of luteinizing hormone (LH), follicles estrogen (FSH), estradiol (E2) and testosterone (T) decrease(P<0.05), levels of visfatin (VF) and leptin (LEP) decreased(P<0.05), adiponectin (APN) increased(P<0.05), and levels of BMI, WHR, hirsutism score and ovarian volume decreased (P<0.05).Compared with the control group(69.44%, 55.56%), the ovulation rate and pregnancy rate in the treatment (91.67%, 80.56%) were higher(P<0.05).Conclusion Gastrointestinal lipase inhibitor combined with biguanides could improve the pregnancy rate and ovulation rate in patients with polycystic ovary syndrome with infertility, reduce the levels of estrogens.%目的:探讨胃肠道脂肪酶抑制剂联合双胍类降糖药对肥胖伴多囊不孕女性血清雌激素水平的影响。方法选取温州医科大学附属黄岩医院内分泌代谢科诊断肥胖伴多囊不孕女性72例,随机分为2组,各36例,对照组予以常规治疗,研究组在常规治疗基础上予以联合奥利司他治疗,采血测定血清学指标,观察临床症状、体征,同时对比妊娠率和排卵率。结果与对照组相比,研究组治疗后血糖和血脂相关指标降低(P<0.05),黄体生成素(luteinizing hormone

  5. Use of biguanides to improve response to chemotherapy.

    Science.gov (United States)

    Sandulache, Vlad C; Yang, Liangpeng; Skinner, Heath D

    2014-01-01

    Metformin is a commonly utilized antidiabetic agent, which has been associated with improved clinical outcomes in cancer patients. The precise mechanism of action remains unclear, but preclinical evidence suggests that metformin can sensitize tumor cells to the effects to conventional chemotherapeutic agents and ionizing radiation (IR). In this chapter we discuss the general background of an approach to evaluate the effects of metformin on conventional chemotherapeutic agent toxicity in a preclinical model.

  6. 双胶束电动毛细管色谱测定复方化学消毒剂中聚六亚甲基单胍、聚六亚甲基双胍、醋酸洗必泰和苄索氯铵%Determination of polyhexamethylene guanide,polyhexamethylene biguanide,chlorhexidine acetate and benzethonium chloride in compound chemical disinfectants by micellar electrokinetic chromatography with bi-micelle

    Institute of Scientific and Technical Information of China (English)

    刘文叶; 乔宏; 赵珊; 李疆; 丁晓静

    2016-01-01

    A new method for the accurate assay of four components( polyhexamethylene gua-nide(PHMG),polyhexamethylene biguanide(PHMB),chlorhexidine acetate(CHA)and benzethonium chloride( BTC))in compound chemical disinfectants by micellar electrokinetic chromatography( MEKC ) with bi-micelle was developed. An uncoated fused-silica capillary with 50 μm i.d. and 50. 2 cm total length( effective length:40 cm)under a separation voltage of 24 kV was used. The separation buffer consisted of 20 mmol/L Na2B4O7,30 mmol/L sodium dodecyl sulfate(SDS),5 mmol/L sodium deoxycholate(SD)and 0. 8 g/L polyethyleneglycol ( PEG)20000. A 1∶10 dilution of the running buffer with ultrapure water was used as the sample buffer. The injection pressure and time were 3. 448 kPa and 12 s,respectively. Liquid samples could be directly injected after dilution with sample buffer. Solid samples were extracted with 10 mL of sample buffer twice and the two extracted solutions were merged together and then di-rectly injected. The factors such as the buffer concentration and pH,the concentrations of SDS and SD,the concentration of PEG 20000 and the sample extraction solution which influence the separation were investigated in detail. The corrected peak areas versus the concentrations of the four components showed good linear relationships within the range from 3 mg/L to 140 mg/L with correlation coefficients( r)greater than 0. 999. The limits of detection( LODs)and the limits of quantification( LOQs)of the four components were all 1 mg/L and 3 mg/L,respec-tively. The average recoveries at three spiked levels were in the range of 84. 1%-109. 6% with RSDs all less than 6%. Eleven samples were analyzed and the results met well with the specified content. The PHMG could be easily discriminated from PHMB. The MEKC method is suitable for the supervision of compound chemical disinfectants.%建立了双胶束电动毛细管色谱(MEKC)分离测定复方化学消毒剂中有效成分聚六亚甲基单胍(PHMG

  7. Time survivor study of Escherichia coli with polyhexamethylene biguanide on cotton

    NARCIS (Netherlands)

    Amrit, Usha Rashmi Bhaskara; Hendrix, Ron; Dutschk, Victoria; Warmoeskerken, Marijn

    2013-01-01

    Time survivor or time kill studies are commonly used to investigate the efficacy of antimicrobial agents in homogeneous solutions. Such a study was attempted via a textile treated with an antimicrobial agent. For this study, a finished undyed cotton fabric and a commercially available antimicrobial

  8. Molecularly imprinted solid-phase extraction for the screening of antihyperglycemic biguanides.

    Science.gov (United States)

    Feng, Sherry Y; Lai, Edward P C; Dabek-Zlotorzynska, Ewa; Sadeghi, Susan

    2004-02-20

    A new molecularly imprinted polymer (MIP) was specifically synthesized as a smart material for the recognition of metformin hydrochloride in solid-phase extraction. Particles of this MIP were packed into a stainless-steel tubing (50 mm x 0.8 mm i.d.) equipped with an exit frit. This micro-column was employed in the development of a molecularly imprinted solid-phase extraction (MISPE) method for metformin determination. The MISPE instrumentation consisted of a micrometer pump, an injector valve equipped with a 20-microl sample loop, a UV detector, and an integrator. With CH3CN as the mobile phase flowing at 0.5 ml/min, 95 +/- 2% binding could be achieved for 1200 ng of metformin from one injection of a phosphate-buffered sample solution (pH 2.5). Methanol + 3% trifluoroacetic acid was good for quantitative pulsed elution (PE) of the bound metformin. The MISPE-PE method, with UV detection at 240 nm, afforded a detection limit of 16 ng (or 0.8 microg/ml) for metformin. However, the micro-column interacted indiscriminately with phenformin with a 49 +/- 2% binding. A systematic investigation of binding selectivity was conducted with respect to sample composition (including the solvent, matrix, pH, buffer and surfactant effects). An intermediate step of differential pulsed elution used acetonitrile with 5% picric acid to remove phenformin and other structural analogues. A final pulsed elution of metformin for direct UV detection was achieved using 3% trifluoroacetic acid in methanol.

  9. Synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 (dimethyl-1-1 biguanide) hydrochloride; Synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 (dimethyl-1-1 biguanide)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M.; Pichat, L. [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1961-07-01

    A description of the synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 hydrochloride passing through the {sup 14}C{sub 2} dicyandiamide. The overall yield with respect to Ba{sup 14}CO{sub 3} is 38 per cent. (author) [French] Description de la synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 par l'intermediaire de la dicyandiamide {sup 14}C{sub 2}. Le rendement global par rapport a {sup 14}CO{sub 3}Ba est de 38 pour cent. (auteur)

  10. 1-邻甲苯基双胍的合成%Synthesis of 1-o-(Tolyl)Biguanide

    Institute of Scientific and Technical Information of China (English)

    鲍欣豪; 魏昌志; 王亚东

    2016-01-01

    合成了一种环氧树脂固化剂1-邻甲苯基双胍.研究了合成条件对反应的影响,并通过正交实验寻找了合适的反应条件.固化实验表明,1-邻甲苯基双胍具有良好的反应活性,固化温度较双氰胺显著降低.

  11. 二甲双胍治疗PCOS临床观察%Two armor biguanides treat the PCOS clinical observation

    Institute of Scientific and Technical Information of China (English)

    刘红艳

    2008-01-01

    目的:观察二甲双胍治疗PCOS的疗效.方法:二甲双胍治疗PCOS患者80例,80例PCOS患者应用二甲双胍500mg/次,3次/天,连续4个月,比较治疗前后体重指数、月经周期、生殖激素水平、排卵率、妊娠率、血糖和胰岛素水平的变化.结果:二甲双胍可降低血LH/FSH比值和雄激素水平(P<0.05),恢复卵巢排卵功能,提高妊娠率,并可降低BMI评分(P<0.05),提高胰岛素的敏感性.结论:二甲双胍单独应用可以改善卵巢的排卵功能,使患者恢复规则的月经周期,降低胰岛素抵抗.

  12. Poly (hexamethylene biguanide) adsorption on hydrogen peroxide treated Ti-Al-V alloys and effects on wettability, antimicrobial efficacy, and cytotoxicity.

    Science.gov (United States)

    Müller, Gerald; Benkhai, Hicham; Matthes, Rutger; Finke, Birgit; Friedrichs, Wenke; Geist, Norman; Langel, Walter; Kramer, Axel

    2014-07-01

    An effective amount of the antiseptic agent PHMB cannot simply be placed on the surface of titanium alloys where hydrocarbons were removed by different purification procedures. Pre-treatment of Ti6Al4V specimen with 5% H2O2 in 24 h results in extra introduced -OH and -COOH groups as well as an adsorbed water film on the surface, which provide the base for the subsequent formation of a relatively stable and multi-layered PHMB film. The superficially adhering PHMB film produces no adverse effects on MG63 cells within a 48 h-cell culture, but promotes the initial attachment and spreading of the osteoblasts on the modified Ti6Al4V surface within 15 min. After direct bacterial inoculation of the active sample, the PHMB film reacts antimicrobially against Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative strains (Pseudomonas aeruginosa, Escherichia coli) after surface contact. The bactericidal efficacy is only slightly reduced after using of the same specimen for re-testing the antibacterial activity. MG63 cells adhere and proliferate within 48 h on a PHMB film-containing Ti6Al4V surface, which has been pre-contaminated with S. aureus. Bacterial biofilms were only revealed in controls without PHMB.

  13. Anti-bacterial and Oder Resistant Agent Containing Biguanide%双胍结构抗菌防臭整理剂

    Institute of Scientific and Technical Information of China (English)

    杨栋樑

    2003-01-01

    对双胍结构的抗菌防臭剂作了评述,介绍其应用方法和应用效果.应用方法有浸轧法、浸渍法和喷淋法三种.此外,还介绍了市售抗菌防臭整理剂商品的性能.

  14. Evaluation of the Merits of Biguanides Hypoglycemic Agents%双胍类降糖药的作用优势与评价

    Institute of Scientific and Technical Information of China (English)

    张石革

    2006-01-01

    目的:糖尿病是一种内分泌-代谢综合征,治疗药物包括降糖药和抗糖尿病药,作用机制各异,而双胍类降糖药独树一帜,本文总结其优势和临床评价.方法:采用国内、外文献综述方法.结果及结论:双胍类降糖药并非刺激胰岛β细胞分泌胰岛素,不受累于胰岛功能与细胞作用,可降低糖合血红蛋白,降低血脂,减少诱发心肌梗死的风险,可作为肥胖和超重的2型糖尿病者的一线用药.

  15. SYNTHESIS OF 1-(p-CARBOXYPHENYL) BIGUANIDE HYDROCHLORIDE%对双胍基苯甲酸盐酸盐的合成

    Institute of Scientific and Technical Information of China (English)

    金绍娣; 姚成; 蔡照胜

    2009-01-01

    实验以对氨基苯甲酸、双氰胺为原料,在盐酸存在下,经对氨基苯甲酸直接与双氰胺反应,一步合成对双胍基苯甲酸盐酸盐.较佳反应条件为:n(盐酸):n(对氨基苯甲酸)=1.:1,反应温度80℃,反应时间6.0h,收率约86%,双胍基苯甲酸盐酸盐质量分数大于97%.

  16. Observation on the disinfectant effect of polyhexamethylene biguanide hydrochloride%聚六亚甲基胍类消毒剂的杀菌效果观察

    Institute of Scientific and Technical Information of China (English)

    王冰姝; 陈惠珍; 钟昱文; 王雅静; 黄美卿; 柯昌文

    2008-01-01

    目的 了解泰成牌消毒液的有效成分聚六亚甲基胍的杀菌效果.方法 采用悬液定量杀菌试验和现场消毒试验方法,进行实验观察.结果 以含13 500mg/L聚六亚甲基胍消毒液,筛选出的中和剂为0.3%卵磷脂、2.0%吐温-80、0.5%硫代硫酸钠、0.1%组氨酸、1.0%皂基的胰蛋白胨生理盐水溶液;对悬液内大肠杆菌和金黄色萄萄球菌作用15min,杀灭对数值>5.00;含13 500mg/L聚六亚甲基胍消毒液浸泡黄瓜15min,平均杀灭对数值为4.02;聚六亚甲基胍消毒液含量13 500mg/L作用15min,对木质物体表面的平均杀灭对数值>3.40.结论 该消毒液性能稳定,杀菌效果好.

  17. 盐酸二甲双胍致不良反应1例%The hydrochloric acid two armor biguanides send respond 1 example

    Institute of Scientific and Technical Information of China (English)

    林莉莉

    2010-01-01

    糖尿病是一种常见病及多发病,往往需要终身治疗,随着糖尿病发病率的不断上升,占糖尿病患者总数90%以上的2型糖尿病患者,治疗方案较多,在药物选择原则上,除了安全性和有效性外,盐酸二甲双胍是治疗糖尿病药物中最经济的品种之一,盐酸二甲双胍不仅能降血糖,且有调节血脂、改变患者对胰岛素敏感性等作用,药物不经肝脏代谢,以原型经尿排出体外,在体内易消除,且能保护心血管免受损害,而且不会引起低血糖.因此,盐酸二甲双胍是治疗2型糖尿病的良好药物.盐酸二甲双胍(Metformin hydrochloride,MFH)是双胍类抗糖尿病药,为目前治疗Ⅱ型糖尿病的首选药物.MFH在胃肠道的吸收不完全,主要吸收部位在小肠.

  18. Clinical Survey of Biguanides with Type 2 Diabetes%2型糖尿病患者双胍类药物的临床应用调查

    Institute of Scientific and Technical Information of China (English)

    李庆光; 荣佐民

    2007-01-01

    目的 观察糖尿病患者双胍类药物的使用情况.方法 对3 a来就诊的糖尿病患者进行登记,调查其用药情况.结果 有超过66%的病人在应用双胍类药物.在有缺氧性疾病的患者中的应用超过50%;并且仍有27%病人还在用降糖灵.结论 一定要强调双胍类药物的禁忌症,提倡合理用药,避免滥用.

  19. HPLC测定盐酸二甲双胍片的有关物质%Determination of the related substances of dimethyl biguanide hydrochloride tablets by HPLC

    Institute of Scientific and Technical Information of China (English)

    韩杰

    2003-01-01

    目的:用HPLC检查盐酸二甲双胍片的有关物质.方法:采用ODS-C18柱(4.6mm× 250mm),甲醇-0.77%醋酸铵(285:115)为流动相,检测波长为232nm.结果:盐酸二甲双胍的理论塔板数大于2 000,盐酸二甲双胍与其杂质的分离度不低于1.5.结论:本方法专属性强,准确,精密,灵敏,适用于该产品的有关物质检查.

  20. 聚氨丙基双胍对蜜橘蒂腐病的作用效果及急性毒性研究%Effect of Polyaminopropyl Biguanide on Diplodia Stem-end Rot Disease of Mandarin Orange and Research the Acute Toxicity of Polyaminopropyl Biguanide

    Institute of Scientific and Technical Information of China (English)

    吴日章

    2015-01-01

    研究聚氨丙基双胍对蜜橘蒂腐病的作用效果,并对聚氨丙基双胍的急性毒性进行研究.结果表明,聚氨丙基双胍对蒂腐病菌具有较好的抑菌效果,质量浓度与抑制率呈正相关性,对蒂腐病菌的EC50为14.04;质量浓度600 mg/L的聚氨丙基双胍对果实接种蒂腐病害具有较好的效果,随着质量浓度的提高,对病害防治效果就越明显;与咪鲜胺复合使用,增强了对柑橘蒂腐病的防治效果,有明显的协同增效作用,当空白组蒂腐发病率为6.59%,聚氨丙基双胍复合咪鲜胺处理组发病率仅为1.52%,有效控制贮藏蜜橘总的发病腐烂率为3.32%;0.2%聚氨丙基双胍的急性经口毒性LD50大于5 000 mg/kg,毒性低、安全性高,可用于蜜橘保鲜、防治蒂腐病,市场前景广阔.

  1. Where does the lactate come from? A rare cause of reversible inhibition of mitochondrial respiration

    OpenAIRE

    Levy, Bruno; Perez, Pierre; Perny, Jessica

    2010-01-01

    Biguanide poisoning is associated with lactic acidosis. The exact mechanism of biguanide-induced lactic acidosis is not well understood. In the previous issue of Critical Care, Protti and colleagues demonstrated that biguanide-induced lactic acidosis may be due in part to a reversible inhibition of mitochondrial respiration. Thus, in the absence of an antidote, increased drug elimination through dialysis is logical.

  2. Density Estimation for New Solid and Liquid Explosives

    Science.gov (United States)

    1977-02-17

    employs biguanide as starting material. Biguanide can be chlorinated to hexachlorobiguanide (1ICB) by treating it with JIOCl in acid solution. IICB is a...reaction of biguanide with HOCI at p11 5, as shown in Equation (37). Although this compound is of no interest in the current program, it has...solution of 2.00 g biguanide (0.02 mol) and 16.4 ml 37% HCI (0.20 mol) in 50 ml water. The biguanide solution was added over a period of 20 min. A

  3. Inhibition of glycolysis and growth of colon cancer cells by 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO in combination with butyrate, 2-deoxy glucose, 3-bromopyruvate or biguanides

    Directory of Open Access Journals (Sweden)

    Lea MA

    2015-09-01

    Full Text Available Introduction: Glycolysis shows a positive correlation with growth of human colon cancer cells. PFKFB3 is an important enzyme regulating glycolysis in many tumor cells and presents a target for cancer chemotherapy. We studied the action of an inhibitor of PFKFB3, 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO, as a single agent and in combination with other molecules that affect glycolysis. Materials and methods: Effects on growth were studied in four human colon cancer cell lines. Glucose metabolism was monitored by uptake from the incubation medium and lactic acid production was judged by acidification of the medium. Induction of alkaline phosphatase served as a marker of differentiation. Results: Growth of colon cancer cells was inhibited by 3PO and butyrate but only butyrate induced activation of alkaline phosphatase. Although metformin and phenformin can increase glucose metabolism, they inhibit colon cancer cell growth and can exert additive inhibitory effects in combination with 3PO. Additive growth inhibitory effects with 3PO were also observed with two compounds that inhibit glycolysis: 2-deoxyglucose and 3-bromopyruvate. Conclusion: 3PO was an inhibitor of growth of colon cancer cells and may be a useful agent in combination with other drugs that inhibit colon cancer cell proliferation.

  4. 双胍类药物引起乳酸酸中毒21例分析%Analysis and treatment of lactic acidosis induced by biguanide drugs in 21 cases

    Institute of Scientific and Technical Information of China (English)

    陈长生

    2011-01-01

    目的 提高对双胍类药物引起的乳酸酸中毒的认识,探讨降低糖尿病乳酸酸中毒病死率的方法.方法 回顾性分析2006年至2010年河南宏力医院收治的21例糖尿病乳酸酸中毒患者的临床资料.结果 老年患者服药依从性不高,双胍类药物使用不当,肝、肾功能损害是服用双胍类药物的糖尿病患者出现乳酸酸中毒的易发因素,严重乳酸酸中毒可引起多器官功能衰竭及死亡.本组21例中9例死亡,死亡组pH值、HCO-3、阴离子间隙较存活组明显下降(P<0.05).结论 严格掌握双胍类降糖药的禁忌证,提高患者的依从性,可减少糖尿病乳酸酸中毒的发病,早期给氧、充分补液、应用葡萄糖加小剂量胰岛素、尽早血液透析是治疗糖尿病乳酸酸中毒成功的关键.

  5. Re-evaluation of biguanides hypoglycemic agents in treating type Ⅱ diabetes%双胍类降糖药物对2型糖尿病治疗价值的重新认识

    Institute of Scientific and Technical Information of China (English)

    陆祖谦

    2010-01-01

    双胍类药物用于治疗2型糖尿病已有50多年.许多国际糖尿病研究组织均推荐以应用二甲双胍和生活方式干预作为2型糖尿病的起始和基础治疗,并贯穿于治疗的始终,除非患者存在严重的肝、肾功能障碍或胃肠疾病.它可和任何降糖药物联合用于2型糖尿病患者的治疗.二甲双胍除了降低血糖外,还具有抗动脉粥样硬化、减少肿瘤发生危险等作用.该文对双胍类药物研究历史,作用及其机制,不良反应等方面进行综述.

  6. Study on Antibacterial Activitiy of Biguanide Benzoyl Chitosan%邻、间、对双胍基苯甲酸盐酸盐抗菌活性的研究

    Institute of Scientific and Technical Information of China (English)

    金绍娣

    2012-01-01

    以邻、间、对氨基苯甲酸为起始原料,在盐酸存在下分别与双氰胺合成了中间体邻、间、对双胍基苯甲酸盐酸盐,分别研究了邻、间、对双胍基苯甲酸盐酸盐对革兰氏菌的抗菌活性.实验表明,邻、间、对双胍基苯甲酸盐酸盐对大肠杆菌、金黄色葡萄球菌都具有抑制作用,抗菌活性随浓度的增加而增强;邻双胍基苯甲酸盐酸盐对大肠杆菌、金黄色葡萄球菌最低抑菌浓度分别为0.064 mg·mL-1和0.032 mg·mL-1,优于间、对双胍基苯甲酸盐酸盐.

  7. Detection of Biguanides Illegally Mixed into Traditional Chinese Medicine Preparations by Liquid Chromatography- mass Spectrometry Method%液相色谱-质谱联用法测定中药制剂中双胍类化学药物

    Institute of Scientific and Technical Information of China (English)

    谭会洁; 凌霄; 王维剑; 郑静

    2007-01-01

    目的 探讨用液相色谱-电喷雾离子阱质谱联用法测定纯中药降糖制剂中非法掺入的双胍类化学药物,包括盐酸二甲双胍、盐酸苯乙双胍.方法 选用Agilent C18柱,以0.02 mol/L醋酸铵溶液(醋酸调节pH值至3.5)-甲醇(30∶70)为流动相,根据所检测到的化合物的色谱保留时间及一级、二级质谱信息,并与对照品比较,测定中药制剂中非法掺入的双胍类化学药物.结果 与结论液相色谱-质谱联用法选择性强,灵敏度高,可作为分析检测非法中药制剂的有效手段.

  8. 二甲双胍治疗多囊卵巢综合征临床疗效分析%Two armor biguanides treat the multi-pouch ovary syndrome clinical curative effect analysis

    Institute of Scientific and Technical Information of China (English)

    邵煜; 王玲

    2010-01-01

    二甲双胍治疗PCOS有一定效果,副反应小,体外研究无致畸作用.对有Ins特别是伴有肥胖的PCOS患者,可选择使用或与促排卵药物联合应用,近期可促使排卵及妊娠,而远期效果是改善糖,脂代谢紊乱,预防或减少糖尿病及心血管的发生.

  9. 对双胍基苯甲酸盐酸盐的制备及其合成条件优化%Preparation of 1-(ρ-Carboxyphenyl)biguanide Hydrochloride and Optimization of the Synthetic Conditions

    Institute of Scientific and Technical Information of China (English)

    金绍娣; 姚成; 蔡照胜

    2010-01-01

    在盐酸存在下,以对氨基苯甲酸和双氰胺为基本原料,一步合成了对双胍基苯甲酸盐酸盐(CPBGH),通过正交实验方法优化了合成条件,用FT IR、~1H NMR和UV表征了产物结构,HPLC分析了产品中CPBGH的含量.结果表明,CPBGH适宜的合成条件为:盐酸与对氨基苯甲酸摩尔比为1.0,反应温度为80℃,反应时间为6.0h;在此条件下,CPBGH的收率为86.1%.UV 分析表明,CPBGH在191 nm、237 nm和269 nm有三个明显的紫外吸收峰;HPLC分析表明,产品中CPBGH的含量达97.22%.

  10. Research on the preparation and antibacterial activity of hydroxypropyl chitosan biguanide hydrochloride membrane with iodine%羟丙基壳聚糖双胍盐酸盐碘膜的制备及抑菌性研究

    Institute of Scientific and Technical Information of China (English)

    谢琳琳; 徐宁宁; 曹焕; 图布新; 王倩; 丁德润

    2016-01-01

    利用“保护氨基-接枝反应-脱保护恢复氨基”方法合成壳聚糖衍生物-羟丙基壳聚糖双胍盐酸盐(HPCGH),并将其与PVP、明胶混合制备相应的衍生物膜HPCGH-PVP,HPCGH-PVP浸没于不同浓度的碘乙醇液中得含碘膜HPCGH-PVP-I2.用FT-IR、XRD、TG和DTG对衍生物进行表征,通过碘量法测定HPCGH-PVP对碘的吸附量.碘含量分析结果表明,HPCGH-PVP吸附碘能力较强,当碘乙醇液浓度为0.03mol/L时,其对碘吸附的最大质量比为m(HPCGH-PVP)∶m(I2)=1∶0.1908.抑菌性测试结果表明,HPCGH-PVP-I2的抑菌性优于HPCGH-PVP,且HPCGH-PVP-I2对E.coli和S.aureus的敏感度均属于高度敏感.

  11. 邻氨基苯甲酸改性双氰胺的制备与表征研究%Characterization and Syntheses of Biguanide Modified Dicyandiamide by o-aminobenzoic Acid

    Institute of Scientific and Technical Information of China (English)

    金绍娣

    2011-01-01

    以邻氨基苯甲酸为基本原料,合成了一种新型的双氰胺衍生物--邻双胍基苯甲酸盐酸盐,讨论了反应条件对合成的影响,并通过熔点、FT-IR、1H-NMR和UV表征了产物结构.结果表明,邻双胍基苯甲酸盐酸盐适宜的合成条件为:邻氨基苯甲酸对双氰胺的物质的量比为1.5、盐酸与邻氨基苯甲酸的物质的量之比为0.6、反应温度为60℃、反应时间为6.0 h;在此条件下,o-CPBGH的收率为37.8%.UV分析表明,o-CPBGH在197 nm、240 nm和272 nm有3个明显的紫外吸收峰.

  12. Evaluation of biguanide in the treatment of IGT: from evidence-baced medicine%二甲双胍治疗糖耐量减低的循证医学研究与评价

    Institute of Scientific and Technical Information of China (English)

    张海燕; 刘国良

    2005-01-01

    葡萄糖耐量减低(impaired glucose tolerance,IGT)是介于正常血糖和糖尿病高血糖之间的一种代谢状态,是正常糖代谢发展到糖尿病的一个过渡阶段,餐后血糖升高是IGT人群的首要特征。IGT的病因和发病机制尚不完全清楚,目前大多数学者认为首先出现胰岛素抵抗,随之发生葡萄糖毒性导致的胰岛分泌胰岛素障碍,必须强调的是,仅有胰岛素抵抗而无胰岛素分泌不足不会发生糖代谢异常,IGT的发生是二者共同作用的结果。

  13. Preparation and Study on Low Molecular Weight Biguanide Benzoyl Chitosan%低分子量双胍基苯甲酰壳聚糖的制备及表征

    Institute of Scientific and Technical Information of China (English)

    吕灯勇; 金绍娣

    2013-01-01

    在简单均相体系下,研究了壳聚糖及双胍基苯甲酰壳聚糖在双氧水中的降解特性.采用高效凝胶渗透色谱法测量了降解过程中壳聚糖及双胍基苯甲酰壳聚糖的分子量变化,讨论了该体系下双胍基苯甲酰低聚壳聚糖及双胍基苯甲酰壳聚糖的胍基化取代度的变化,通过红外光谱分析了低分子量双胍基苯甲酰壳聚糖结构.结果表明,在降解反应温度为65℃、H2O2质量百分浓度为3.0%、盐酸浓度为1.0%时,反应时间的延长会导致低聚壳聚糖或对双胍基苯甲酰壳聚糖低分子化产物相对分子量的逐渐降低,胍基化取代度也随之降低;红外光谱表明,采用该降解体系制备的降解产物主链结构基本没有发生变化.

  14. TLC Building of Biguanide Illegally Mixed into hypoglycemic proprietary Chinese Medicines and Health Food%薄层色谱法检测降糖中药及保健品非法添加的双胍类成分

    Institute of Scientific and Technical Information of China (English)

    张宏莲; 李莉; 许凤; 李静辉; 刘军; 李宏铃

    2013-01-01

    目的:建立检测降糖中药及保健品非法添加双胍类成分的薄层色谱检查方法.方法:样品用乙醇溶解后直接点于硅胶GF254薄层板上;展开剂为石油醚-甲醇-冰乙酸(5∶12∶0.5);薄层扫描条件:测定波长324 nm,参比波长400 nm,线性参数SX=3,狭缝宽度0.4 mm×0.4 mm,灵敏度中等.结果:本实验建立的条件能够把降糖中成药和保健食品中二胍类成分(二甲双胍,苯乙双胍)进行较好的分离,对六种中药降糖药进行检测,与相应标准物质比较,其中三种保健药品中,非法添加了二胍类成分.结论:本法简便、快速、成本低,可用于降糖中药及保健品非法添加双胍类成分的常规检查.

  15. The Nokh dragon unites two armor biguanides to treat 2 diabetes%诺和龙联合二甲双胍治疗2型糖尿病

    Institute of Scientific and Technical Information of China (English)

    陈静

    2010-01-01

    目的:探讨单用二甲双胍与其联合诺和龙治疗2型糖尿病(T2DM)的疗效.方法:60例患者分成两组,单用二甲双胍(对照组)和诺和龙联合二甲双胍(治疗组)各30例.治疗组用二甲双胍0.5g/次,3次/d;诺和龙1mg/次,3次/d.对照组单用二甲双胍0.5g/次,3次/d.分别于用药前、用药半个月、1个月及2个月后查空腹血糖、餐后2小时血糖,用药前及用药2个月查糖化血红蛋白.结果:治疗组的血糖及血红蛋白下降幅度较对照组增大,尤其是餐后2小时血糖的下降幅度增大明显.患者对诺和龙有较好的耐受性,尤其是低血糖的发生率明显降低.结论:诺和龙与二甲双胍联用治疗T2DM 具有协同作用,副作用少,效果明显优于单用二甲双胍治疗,同时可改善T2DM患者对治疗的顺应性.

  16. Analysis of 52 cases with lactic acidosis induced by biguanide drugs%双胍类药物引起乳酸酸中毒52例分析

    Institute of Scientific and Technical Information of China (English)

    徐昌盛; 刘文革; 黄英姿

    2010-01-01

    目的 提高对双胍类药物引起的乳酸酸中毒的认识.方法 在中国期刊全文数据库中(1994-2007年)检索,对符合诊断标准的41篇病例报告文献进行分析.结果 共52例患者,其中苯乙双胍40例,二甲双胍12例,63.5%(33/52)的乳酸酸中毒与超量服用双胍类药物有关.发生乳酸酸中毒后,血乳酸和阴离子间隙显著升高,动脉血pH 和HCO3-显著下降,死亡组pH值和HCO3-较存活组明显下降(P<0.01).17例死亡者中,11例死于严重休克.结论 双胍类药物使用不当是发生乳酸酸中毒的重要原因,代谢性酸中毒伴阴离子间隙增高是此类酸中毒的主要特征,休克是死亡的主要原因.

  17. Evaluation of Chemotherapeutic Agents Against Malaria, Drugs, Diet, and Biological Response Modifiers.

    Science.gov (United States)

    1991-10-29

    observed between WR 238417, the putative biguanide precursor of a triazine (WR 99210), and both sulfadiazine and pyrime- thamine against pyrimethamine...bisquinolines (BM 03821) was more active and less toxic than BL 57511. Synergistic activity was observed between WR 238417, the putative biguanide ...intervals until day 60 postinfection. Survival times were also monitored for this 60 day period. In experiment 680 WR 250417, the putative biguanide

  18. Research and Operational Support for the Study of Military Relevant Infectious Diseases of Interest to United States and Royal Thai Government

    Science.gov (United States)

    2006-01-01

    interactions in humans. (AQ0012_04_WR: Drug-drug interaction study of artesunate in rhesus monkey). Between Mar-June 05, five biguanide analogs were...parent drugs and their putative metabolites were measured by LC/MS. The pharmacokinetic/pharmacodynamic profiles of the biguanide compounds were...characterized and a common unknown metabolite was identified following administration of 3 compounds. (A40005_04_AF: PK/PD screen of lead biguanides and

  19. Use of thiazolidinediones and risk of bladder cancer

    DEFF Research Database (Denmark)

    Bazelier, Marloes T; de Vries, Frank; Vestergaard, Peter;

    2013-01-01

    ) of bladder cancer were estimated using Cox proportional hazards models. Time-dependent adjustments were made for age, comorbidity, and drug use. Four different treatment stages were defined: current use of either a biguanide or a sulfonylureum (stage 1), current use of a biguanide and a sulfonylureum...

  20. Involvement of organic cation transporter 1 in the lactic acidosis caused bv metformin

    NARCIS (Netherlands)

    Wang, DS; Kusuhara, H; Kato, Y; Jonker, JW; Schinkel, AH; Sugiyama, Y

    2003-01-01

    Biguanides are a class of drugs widely used as oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus, but they are associated with lactic acidosis, a lethal side effect. We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a

  1. Comparison of Effect and Adverse Reaction of Pioglitazone and Dimethyl Biguanide on Patients with Type 2 Diabetes Mellitus Latest Diagnosed%2型糖尿病应用吡格列酮和二甲双胍的作用比较

    Institute of Scientific and Technical Information of China (English)

    孟凡良

    2006-01-01

    目的探讨吡格列酮及二甲双胍对新诊断的2型糖尿病降糖作用及不良反应.方法我们选择126例新诊断2型糖尿病,随机分为两组,单用吡格列酮或二甲双胍以观察其降低作用及不良反应.结果吡格列酮组及二甲双胍组均为63例.二甲双胍用药1~3周开始下降,至第4周下降明显,而吡格列酮组至第8周下降明显,至16周无继续下降.不良反应发生率:吡格列酮26.8%,二甲双胍为41%.结论对新诊断2型糖尿病无论是二甲双胍或吡格列酮均可使空腹及餐后的血糖、糖化血红蛋白明显下降.

  2. Identification of two kinds of biguanides illegally added to traditional Chinese medicines and health products by TLC-IR%TLC-IR法检测降糖中药及保健品中掺入2种双胍类药物

    Institute of Scientific and Technical Information of China (English)

    张宏莲; 李莉; 李智; 刘吉成; 李冲冲; 董毅峰; 孙洪刚; 黄海涛

    2013-01-01

    目的:建立降糖中药及保健品中非法添加2种双胍类药物的快速检测方法.方法:采用硅胶GF254薄层板,乙酸乙酯-甲醇-冰醋酸(5∶6∶0.5)为展开剂,展开制备薄层斑点,测其红外光谱.结果:建立的TLC-IR法对降糖中成药及保健品共计6个品种12批次进行检测,其中3种保健品非法添加了双胍类成分.结论:方法简便易行、专属性较强,可用TLC-IR法对降糖中药及保健品中掺入的化学降糖药物进行快速检测.

  3. 短期双胍类降糖药治疗对糖尿病患者血乳酸水平的影响%Effects of short-term biguanides treatment for diabetes on the levels of plasma lactic acid

    Institute of Scientific and Technical Information of China (English)

    罗国春; 李海燕; 梁真; 李明政; 陈泽龙; 欧慧婷

    2008-01-01

    目的:观察短期苯乙双胍和二甲双胍治疗高龄2型糖尿病(DM)患者对血浆乳酸水平的影响.方法: 苯乙双胍组为16例高龄(60~74岁)2型DM患者,每日服用苯乙双胍150 mg,连续7 d;二甲双胍组为16例高龄(60~76岁)2型DM患者,每日服用二甲双胍1.5 g,连续7 d.于服药前、服药1~7 d,每日监测血浆乳酸水平的变化.结果: 苯乙双胍组服药后血乳酸水平[分别为(2.64 ±0.74)、(2.76±0.72)、(3.42 ±1.01)、(3.44±0.78)、(3.67±0.78)、(3.74±0.87)、(3.76±0.86)mmol·L -1]较服药前水平[(2.32±0.59)mmol·L-1]显著增高(F=7.833,P=0.000).二甲双胍组服药前后血浆水平无明显变化(F=0.942,P=0.479).结论:高龄2型DM患者短期服用苯乙双胍可以引起血浆乳酸水平明显增高,继续服用有发生乳酸酸中毒的倾向.

  4. HPLC/MS2法检测某些降糖中药制剂中的双胍类及磺酰脲类化学药%HPLC/MS2 detection of biguanides and sulfonylurea antidiabetics illegally mixed into traditional Chinese preparations

    Institute of Scientific and Technical Information of China (English)

    钟丽红; 凌霄; 孙华

    2008-01-01

    目的:建立液相色谱-电喷雾离子阱质谱联用法测定纯中药降糖药中非法掺入的双胍类及磺酰脲类化学药,包括二甲双胍、苯乙双胍、格列吡嗪、格列本脲、格列美脲、格列喹酮、格列齐特.方法:选用Agilent C18(4.6 mm×150 mm,5 μm),以0.02 mol·L-1醋酸铵溶液(醋酸调节pH至3.5)-甲醇-乙腈为流动相,梯度洗脱.根据所检测到化合物的色谱保留时间及一级、二级质谱信息,并与对照品比较,鉴别中药制剂中非法掺入的双胍类、酰脲类化学药.结果:通过相对分子质量、二级质谱碎片信息和液相色谱保留时间三方面信息,与对照品比较,证明样品A中非法掺有苯乙双胍、格列本脲,样品B中掺有二甲双胍、格列本脲.结论:该方法选择性强,灵敏度高,可作为分析检测非法中药制剂的有效手段.

  5. The treatment of old age coal worker's pneumoconiosis with repaglinide combined with dimethyl biguanide%瑞格列奈二甲双胍联合治疗老年煤工尘肺合并2型糖尿病临床观察

    Institute of Scientific and Technical Information of China (English)

    庞德友; 任明伟

    2006-01-01

    目的观察瑞格列奈、二甲双胍联合治疗老年煤工尘肺合并2型糖尿病的疗效.方法 32例煤工尘肺合并2型糖尿病患者服用瑞格列奈0.5~10 mg,Tid;二甲双胍0.5g,Tid,疗程12周.监测治疗前后体重、空腹血糖(FBG)、餐后2小时血糖(PBG)、糖化血红蛋白(HbA1C)、肝、肾功能.结果FBG下降4.97mmol/L,PBG下降8.04 mmol/L,HbA1C下降1.94%,较治疗前均显著下降(P<0.001);体重,肝、肾功能无变化;无严重低血糖发生.结论瑞格列奈与二甲双胍联合治疗老年煤工尘肺合并2型糖尿病具有降糖作用好、安全性、耐受性良好的特点.

  6. 联合应用阿托伐他汀和二甲双胍治疗混合性高脂血症的疗效及安全性观察%The effects and safety of atorvastatin combines with dimethyl biguanide in patients with combined hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    林雪芳; 李平

    2008-01-01

    目的 观察联合应用阿托伐他汀和二甲双胍治疗混合性高脂血症的疗效及安全性.方法 选择混合性高脂血症患者168例,随机分为二组:(A)阿托伐他汀组80例,(B)阿托伐他汀和二甲双胍联合治疗组88例.观察治疗前和治疗后12w的TC、TG、LDL-C及HDL-C的血清浓度变化.结果 联合治疗组治疗后TC、LDL-C、TG三项较单药治疗组更易达标,两组间有显著性差异(P<0.01).结论 对于混合性高脂血症患者,阿托伐他汀联合二甲双胍治疗较阿托伐他汀单药治疗能更有效地使TC、LDL-C、TG达标,而且联合应用治疗混合性高脂血症价廉、安全、有效.

  7. CLINICAL OBSERVATION OF TYPE 2 DIABETS TREATED WITH GANSHULIN AND DIMETHYL BIGUANIDE WHICH WERE FAIL TREATED WITH SULFONYLUREA%甘舒霖合二甲双胍治疗磺脲类药物失效之2型糖尿病的临床观察

    Institute of Scientific and Technical Information of China (English)

    罗燕; 李少萍

    2006-01-01

    目的观察胰岛素合二甲双胍治疗磺脲类药物失效之2型糖尿病的疗效.方法将70例磺脲类药物失效的2型糖尿病患者随机分为治疗组(35例)和对照组(35例),对照组改予二甲双胍治疗,治疗组在对照组的基础上加予胰岛素治疗.结果治疗组治疗后空腹血糖、餐后2小时血糖、HbA1c均明显降低达理想水平,且无出现低血糖反应.结论胰岛素合二甲双胍治疗磺脲类药物失效之2型糖尿病有利于血糖控制.

  8. Curative effect of glutathione united with two armor biguanide on type 2 diabetes mellitus complicated with fatty liver%还原型谷胱甘肽联合二甲双胍治疗2型糖尿病并发脂肪肝疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈星浩; 宁小艳; 张静

    2006-01-01

    ①目的探讨还原型谷胱甘肽(GSH)联合二甲双胍(metformin)治疗糖尿病并发脂肪肝的疗效.②方法 48例糖尿病并发脂肪肝患者,均在运动与饮食治疗基础上,常规护肝治疗;用还原型谷胱甘肽1 200mg, 加入5%葡萄糖注射液250mL中,每日1次,静脉滴注,每次口服二甲双胍片0.25g,每日3次.3个月为一疗程,观察有关指标及B超影像学改变.③结果经治疗后患者丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)降至正常(P<0.001),血总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及体重指数(BMI)值较治疗前显著降低(P﹤0.001),空腹血糖(FPG)、糖化血红蛋白(HbA1c)较治疗前下降(P<0.001),计算比较稳态模式胰岛素抵抗指数(HOMA-IR)和稳态模式胰岛素敏感指数(HOMA-IAI)值,差异具有显著性意义(P<0.005).④结论对伴有脂肪肝的2型糖尿病患者应用还原型谷胱甘肽联合二甲双胍治疗,能有效地改善胰岛素抵抗,提高胰岛素敏感性,具有降酶、降糖、调脂的功效,疗效较好.

  9. Drug: D10301 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10301 Mixture, Drug Chlorhexidine gluconate - alcohol mixt; Prevantics (TN) Chlorh...ISINFECTANTS D08AC Biguanides and amidines D08AC52 Chlorhexidine, combinations D10301 Chlorhexidine gluconate - alcohol mixt PubChem: 163312332 ...

  10. Synergistic Interaction between Metformin and Sulfonylureas on Diclofenac-Induced Antinociception Measured Using the Formalin Test in Rats

    Directory of Open Access Journals (Sweden)

    Mario I Ortiz

    2013-01-01

    Full Text Available BACKGROUND: There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA.

  11. Type 2 diabetes

    Science.gov (United States)

    ... medicines (GLP-1 analogs) Meglitinides SGL T2 inhibitors Sulfonylureas Thiazolidinediones You may need to take insulin if ... rule Glucose in blood Alpha-glucosidase inhibitors Biguanides Sulfonylureas drug Thiazolidinediones Food and insulin release Monitoring blood ...

  12. Metformin: do we finally have an anti-aging drug?

    Science.gov (United States)

    Anisimov, Vladimir N

    2013-11-15

    Studies in mammals have demonstrated that hyperglycemia and hyperinsulinemia are important factors in aging and cancer. Inactivation of insulin/insulin-like signaling increases lifespan in nematodes, fruit flies, and mice. Life-prolonging effects of caloric restriction are in part due to reduction in IGF-1, insulin, and glucose levels. Antidiabetic biguanides such as metformin, which reduce hyperglycemia and hyperinsulinemia by decreasing insulin resistance, extend lifespan, and inhibit carcinogenesis in rodents. Will antidiabetic biguanides increase lifespan in humans?

  13. ROLE FAILURE CORRECTION OF 25(OH)D IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME

    OpenAIRE

    2015-01-01

    Objective. To estimate the correction failure 25 (OH) D in patients with polycystic ovary syndrome.Material and Methods. The study involved 44 patients with polycystic ovary syndrome, aged 31.32 ± 5.05, who were randomly assigned to 2 groups: 1st – obtained coca biguanides and Kolekaltsiferol, second – combined oral contraceptive (combined hormonal ) and biguanides. The comparison group consisted of 22 healthy women matched for age and sex. Polycystic Ovarian Syndrome (PCOS) was verified on t...

  14. Effects of Metformin, Buformin, and Phenformin on the Post Initiation Stage of Chemically-Induced Mammary Carcinogenesis in the Rat

    OpenAIRE

    2015-01-01

    Metformin is a widely prescribed drug for the treatment of type-2 diabetes. Although epidemiological data have provided a strong rationale for investigating the potential of this biguanide for use in cancer prevention and control, uncertainty exists whether metformin should be expected to have an impact in non-diabetic patients. Furthermore, little attention has been given to the possibility that other biguanides may have anticancer activity. In this study, the effects of clinically relevant ...

  15. Metformin for cancer and aging prevention: is it a time to make the long story short?

    OpenAIRE

    2015-01-01

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutan...

  16. Drug: D02206 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available pocytokine signaling pathway map07051 Antidiabetics Therapeutic category of drugs in Japan [BR:br08301] 3 Ag...ents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3962 Biguanides D0220...D02206 Drug Buformin hydrochloride (JP16); Dibetos-B (TN) C6H15N5. HCl 193.1094 193.6777 D02206.gif Antidiab...etic [DS:H00409] Therapeutic category: 3962 ATC code: A10BA03 biguanides AMPK activ

  17. Cellular Responses to the Metal-Binding Properties of Metformin

    Science.gov (United States)

    Logie, Lisa; Harthill, Jean; Patel, Kashyap; Bacon, Sandra; Hamilton, D. Lee; Macrae, Katherine; McDougall, Gordon; Wang, Huan-Huan; Xue, Lin; Jiang, Hua; Sakamoto, Kei; Prescott, Alan R.; Rena, Graham

    2012-01-01

    In recent decades, the antihyperglycemic biguanide metformin has been used extensively in the treatment of type 2 diabetes, despite continuing uncertainty over its direct target. In this article, using two independent approaches, we demonstrate that cellular actions of metformin are disrupted by interference with its metal-binding properties, which have been known for over a century but little studied by biologists. We demonstrate that copper sequestration opposes known actions of metformin not only on AMP-activated protein kinase (AMPK)-dependent signaling, but also on S6 protein phosphorylation. Biguanide/metal interactions are stabilized by extensive π-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding. In contrast, regulation of S6 phosphorylation is prevented only by direct modification of the metal-liganding groups of the biguanide structure, supporting recent data that AMPK and S6 phosphorylation are regulated independently by biguanides. Additional studies with pioglitazone suggest that mitochondrial copper is targeted by both of these clinically important drugs. Together, these results suggest that cellular effects of biguanides depend on their metal-binding properties. This link may illuminate a better understanding of the molecular mechanisms enabling antihyperglycemic drug action. PMID:22492524

  18. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.

    Science.gov (United States)

    Janzer, Andreas; German, Natalie J; Gonzalez-Herrera, Karina N; Asara, John M; Haigis, Marcia C; Struhl, Kevin

    2014-07-22

    Metformin, a first-line diabetes drug linked to cancer prevention in retrospective clinical analyses, inhibits cellular transformation and selectively kills breast cancer stem cells (CSCs). Although a few metabolic effects of metformin and the related biguanide phenformin have been investigated in established cancer cell lines, the global metabolic impact of biguanides during the process of neoplastic transformation and in CSCs is unknown. Here, we use LC/MS/MS metabolomics (>200 metabolites) to assess metabolic changes induced by metformin and phenformin in an Src-inducible model of cellular transformation and in mammosphere-derived breast CSCs. Although phenformin is the more potent biguanide in both systems, the metabolic profiles of these drugs are remarkably similar, although not identical. During the process of cellular transformation, biguanide treatment prevents the boost in glycolytic intermediates at a specific stage of the pathway and coordinately decreases tricarboxylic acid (TCA) cycle intermediates. In contrast, in breast CSCs, biguanides have a modest effect on glycolytic and TCA cycle intermediates, but they strongly deplete nucleotide triphosphates and may impede nucleotide synthesis. These metabolic profiles are consistent with the idea that biguanides inhibit mitochondrial complex 1, but they indicate that their metabolic effects differ depending on the stage of cellular transformation.

  19. Metformin for cancer and aging prevention: is it a time to make the long story short?

    Science.gov (United States)

    Anisimov, Vladimir N

    2015-11-24

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutant), spontaneous (non- exposed to any carcinogenic agent) or induced by 16 chemical carcinogens of different classes (polycycIic aromatic hydrocarbons, nitroso compounds, estrogen, etc.), direct or indirect (need metabolic transformation into proximal carcinogen), by total body X-rays and γ- irradiation, viruses, genetic modifications or special high fat diet, using one stage and two-stage protocols of carcinogenesis, 5 routes of the administration of antidiabetic biguanides (oral gavage, intraperitoneal or subcutaneous injections, with drinking water or with diet) in a wide ranks of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. Very important that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides. It was conclude that there is sufficient experimental evidence of anti-carcinogenic effect of antidiabetic biguanides.

  20. Metformin for cancer and aging prevention: is it a time to make the long story short?

    Science.gov (United States)

    Anisimov, Vladimir N.

    2015-01-01

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutant), spontaneous (non- exposed to any carcinogenic agent) or induced by 16 chemical carcinogens of different classes (polycycIic aromatic hydrocarbons, nitroso compounds, estrogen, etc.), direct or indirect (need metabolic transformation into proximal carcinogen), by total body X-rays and γ- irradiation, viruses, genetic modifications or special high fat diet, using one stage and two-stage protocols of carcinogenesis, 5 routes of the administration of antidiabetic biguanides (oral gavage, intraperitoneal or subcutaneous injections, with drinking water or with diet) in a wide ranks of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. Very important that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides. It was conclude that there is sufficient experimental evidence of anti-carcinogenic effect of antidiabetic biguanides. PMID:26583576

  1. AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B.

    Science.gov (United States)

    Bertrand, Luc; Ginion, Audrey; Beauloye, Christophe; Hebert, Alexandre D; Guigas, Bruno; Hue, Louis; Vanoverschelde, Jean-Louis

    2006-07-01

    Diabetic hearts are known to be more susceptible to ischemic disease. Biguanides, like metformin, are known antidiabetic drugs that lower blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in muscle. Part of these metabolic effects is thought to be mediated by the activation of AMP-activated protein kinase (AMPK). In this work, we studied the relationship between AMPK activation and glucose uptake stimulation by biguanides and oligomycin, another AMPK activator, in both insulin-sensitive and insulin-resistant cardiomyocytes. In insulin-sensitive cardiomyocytes, insulin, biguanides and oligomycin were able to stimulate glucose uptake with the same efficiency. Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive. In insulin-resistant cardiomyocytes, where insulin stimulation of glucose uptake was greatly reduced, biguanides or oligomycin, in the absence of insulin, induced a higher stimulation of glucose uptake than that obtained in insulin-sensitive cells. This stimulation was correlated with the activation of both AMPK and PKB and was sensitive to the phosphatidylinositol-3-kinase/PKB pathway inhibitors. Finally, an adenoviral-mediated expression of a constitutively active form of AMPK increased both PKB phosphorylation and glucose uptake in insulin-resistant cardiomyocytes. We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB. Our results suggest that AMPK activation could restore normal glucose metabolism in diabetic hearts and could be a potential therapeutic approach to treat insulin resistance.

  2. Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment

    Science.gov (United States)

    Menendez, Javier A.; Quirantes-Piné, Rosa; Rodríguez-Gallego, Esther; Cufí, Sílvia; Corominas-Faja, Bruna; Cuyàs, Elisabet; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; Segura-Carretero, Antonio; Joven, Jorge

    2014-01-01

    “The dose makes the poison”, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to “diabetobiguanides” with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to “oncobiguanides” with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides. PMID:24909934

  3. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin

    NARCIS (Netherlands)

    Wang, DS; Jonker, JW; Kato, Y; Kusuhara, H; Schinkel, AH; Sugiyama, Y

    2002-01-01

    Metformin, a biguanide, is widely used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus. The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin. Transfection of rat Oct1 cDNA results in the time-d

  4. Drug: D08399 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08399 Drug Polihexanide (INN); Polyhexanide; Lavasept (TN) (C8H17N5. HCl)n D08399....LOGICALS D08 ANTISEPTICS AND DISINFECTANTS D08A ANTISEPTICS AND DISINFECTANTS D08AC Biguanides and amidines D08AC05 Polihexani...de D08399 Polihexanide (INN) CAS: 32289-58-0 PubChem: 96025085

  5. Drug: D00595 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available diabetics Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] A ALIMENTARY TRACT AND METABOLISM A10 DRUGS USED IN DIABE...TES A10B BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS A10BA Biguanides A10BA03 Bufo

  6. Drug: D08351 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available [HSA:1565] Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] A ALIMENTARY TRACT AND METABOLISM A10 DRUGS USED IN DIAB...ETES A10B BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS A10BA Biguanides A10BA01 Phe

  7. Enterobacteriaceae and Salmonella recovered from non-sanitized and sanitized broiler hatching eggs

    Science.gov (United States)

    Sanitizing hatching eggs may reduce the chances that a flock will become colonized with Salmonella and reduce the numbers of other microorganisms, such as Enterobacteriaceae, that can depress hatchability. An experiment was conducted to determine if a quaternary-biguanide sanitizer applied as foam ...

  8. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

    DEFF Research Database (Denmark)

    Chindera, Kantaraja; Mahato, Manohar; Sharma, Ashwani Kumar;

    2016-01-01

    To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption...

  9. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Taskiran, M; Toft-Nielsen, M B;

    2001-01-01

    OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted...

  10. History of current non-insulin medications for diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Celeste C. L. Quianzon

    2012-10-01

    Full Text Available This article is a brief review of the current non-insulin agents for diabetes mellitus in the United States, namely, sulfonylureas, biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, glucacon-like peptide-1 receptor agonists, dipeptidyl-peptidase-4 inhibitors, amylin agonists, bromocriptine, and colesevelam.

  11. Effects of metformin, buformin, and phenformin on the post-initiation stage of chemically induced mammary carcinogenesis in the rat.

    Science.gov (United States)

    Zhu, Zongjian; Jiang, Weiqin; Thompson, Matthew D; Echeverria, Dimas; McGinley, John N; Thompson, Henry J

    2015-06-01

    Metformin is a widely prescribed drug for the treatment of type II diabetes. Although epidemiologic data have provided a strong rationale for investigating the potential of this biguanide for use in cancer prevention and control, uncertainty exists whether metformin should be expected to have an impact in nondiabetic patients. Furthermore, little attention has been given to the possibility that other biguanides may have anticancer activity. In this study, the effects of clinically relevant doses of metformin (9.3 mmol/kg diet), buformin (7.6 mmol/kg diet), and phenformin (5.0 mmol/kg diet) were compared with rats fed control diet (AIN93-G) during the post-initiation stage of 1-methyl-1-nitrosourea-induced (50 mg/kg body weight) mammary carcinogenesis (n = 30/group). Plasma, liver, skeletal muscle, visceral fat, mammary gland, and mammary carcinoma concentrations of the biguanides were determined. In comparison with the control group, buformin decreased cancer incidence, multiplicity, and burden, whereas metformin and phenformin had no statistically significant effect on the carcinogenic process relative to the control group. Buformin did not alter fasting plasma glucose or insulin. Within mammary carcinomas, evidence was obtained that buformin treatment perturbed signaling pathways related to energy sensing. However, further investigation is needed to determine the relative contributions of host systemic and cell autonomous mechanisms to the anticancer activity of biguanides such as buformin.

  12. The mechanism of the acute hypoglycemic action of phenformin (DBI).

    Science.gov (United States)

    Searle, G L; Gulli, R

    1980-07-01

    The mechanisms by which biguanide (phenformin) acutely brings about a reduction in blood glucose in diabetic subjects has been studied with the aid of C-6 14C glucose. Six diabetic subjects were studied, each at three separate dose levels of phenformin. Two of these same subjects were studied with placebo. Consistent and increasingly pronounced effects of drug versus placebo were noted as the level of biguanide was increased. Biguanide consistently lowered hepatic glucose output while not significantly affecting the removal of glucose from the circulation. It was noted that glucogenesis from lactate was not significantly curtailed. However, a lack of stimulation in Cori Cycle activity in the presence of significant elevations of circulating lactate were taken as an indication of inhibition of glucogenesis from this substrate. On balance, it is concluded that the acute hypoglycemic action of this biguanide is mediated primarily through a restriction in the supply of glucose from the liver to the circulation. The data support the contention that these drugs inhibit hepatic glucogenesis even though Cori Cycle activity may be increased and also suggest that a portion of the decrease in hepatic glucose supply may be the result of impaired glycogenolysis.

  13. Comparison of baseline characteristics and clinical course in Japanese patients with type 2 diabetes among whom different types of oral hypoglycemic agents were chosen by diabetes specialists as initial monotherapy (JDDM 42)

    Science.gov (United States)

    Fujihara, Kazuya; Igarashi, Risa; Matsunaga, Satoshi; Matsubayashi, Yasuhiro; Yamada, Takaho; Yokoyama, Hiroki; Tanaka, Shiro; Shimano, Hitoshi; Maegawa, Hiroshi; Yamazaki, Katsuya; Kawai, Koichi; Sone, Hirohito

    2017-01-01

    Abstract Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i.e., either sulfonylureas, biguanides, or DPP-4 inhibitors (DPP-4Is)) were chosen as initial monotherapy by diabetes specialists and evaluated subsequent usage patterns. Prescription data on 3 different antidiabetic agents from December 2009 to March 2015 from diabetes specialists’ patient registries were used to identify variables at baseline related to initial prescriptions; also, the addition of another hypoglycemic drug or discontinuation of the initial therapy was evaluated 1 year after the initial prescription. Analyzed were data on 2666 patients who received initial monotherapy with either a sulfonylurea (305 patients), biguanide (951 patients), or DPP-4I (1410 patients). Patients administered sulfonylureas were older, had a lower body mass index (BMI), longer duration of diabetes, and worse glycemic control than recipients of biguanides. Use of biguanides was related to younger age, short duration of diabetes, and obesity but was negatively associated with poor glycemic control. Older age but neither obesity nor poor glycemic control was associated with DPP-4Is. In all 3 groups a high HbA1c value was related to adding another hypoglycemic agent to the initial therapy. Moreover, adding another drug to a DPP-4I was related to a younger age and higher BMI. Patients’ age, duration of diabetes, obesity, and glycemic control at baseline influenced the choice of hypoglycemic agents

  14. Understanding the benefit of metformin use in cancer treatment

    Directory of Open Access Journals (Sweden)

    Goodwin Pamela J

    2011-04-01

    Full Text Available Abstract Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed.

  15. Activity of disinfectants against foodborne pathogens in suspension and adhered to stainless steel surfaces

    Directory of Open Access Journals (Sweden)

    Tatiane Karen Cabeça

    2012-09-01

    Full Text Available The purpose of this study was to investigate and compare the efficacy of various disinfectants on planktonic cells and biofilm cells of Listeria monocytogenes, Staphylococcus aureus and Escherichia coli. Numbers of viable biofilm cells decreased after treatment with all tested disinfectants (iodine, biguanide, quaternary ammonium compounds, peracetic acid and sodium hypochlorite. Sodium hypochlorite was the most effective disinfectant against biofilm cells, while biguanide was the least effective. Scanning electron microscopy observations revealed that cells adhered on stainless steel surface after treatment with the disinfectants. No viable planktonic cells were observed after treatment with the same disinfectants. Based on our findings, we concluded that biofilm cells might be more resistant to disinfectants than plancktonic cells.

  16. Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

    OpenAIRE

    Takiyama, Yumi; Harumi, Tatsuo; Watanabe, Jun; Fujita, Yukihiro; Honjo, Jun; Shimizu, Norihiko; Makino, Yuichi; Haneda, Masakazu

    2011-01-01

    OBJECTIVE Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxia-inducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DESIGN AND METHODS We explored the effects of metformin on the expression of HIF-1α using human renal pro...

  17. Metformin attenuates lung fibrosis development via NOX4 suppression

    OpenAIRE

    Sato, Nahoko; Takasaka, Naoki; Yoshida, Masahiro; Tsubouchi, Kazuya; Minagawa,Shunsuke; Araya,Jun; Saito, Nayuta; Fujita, Yu; Kurita, Yusuke; KOBAYASHI, KENJI; ITO, Saburo; Hara, Hiromichi; Kadota, Tsukasa; Yanagisawa, Haruhiko; Hashimoto,Mitsuo

    2016-01-01

    Background Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action i...

  18. Metformin and Diabetic Kidney Disease: A Mini-Review on Recent Findings

    OpenAIRE

    Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Metformin, an oral anti-diabetic agent in the biguanide class is a widely prescribed drug to treat high blood glucose in patients with type 2 diabetes mellitus. Metformin has three different roles, including blood glucose regulatory effect, protection of kidney tubular cell by acting as an effective antioxidant and finally ameliorative effect on diabetic kidney disease through saving the podocytes. Therefore, diabetic patients may benefit from all of these three distinct ameliorative effects.

  19. Metformin and diabetic kidney disease: a mini-review on recent findings.

    Science.gov (United States)

    Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-10-01

    Metformin, an oral anti-diabetic agent in the biguanide class is a widely prescribed drug to treat high blood glucose in patients with type 2 diabetes mellitus. Metformin has three different roles, including blood glucose regulatory effect, protection of kidney tubular cell by acting as an effective antioxidant and finally ameliorative effect on diabetic kidney disease through saving the podocytes. Therefore, diabetic patients may benefit from all of these three distinct ameliorative effects.

  20. Intracerebroventricular Injection of Metformin Induces Anorexia in Rats

    OpenAIRE

    2012-01-01

    Background Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known. Methods To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides asso...

  1. The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

    Directory of Open Access Journals (Sweden)

    Linda A. Villani

    2016-10-01

    Conclusion: These data indicate that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations.

  2. Formation of the diuretic chlorazanil from the antimalarial drug proguanil--implications for sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Tretzel, Laura; Bailloux, Isabelle; Buisson, Corinne; Lasne, Francoise; Schaefer, Maximilian S; Kienbaum, Peter; Mueller-Stoever, Irmela; Schänzer, Wilhelm

    2015-11-10

    Chlorazanil (Ordipan, N-(4-chlorophenyl)-1,3,5-triazine-2,4-diamine) is a diuretic agent and as such prohibited in sport according to the regulations of the World Anti-Doping Agency (WADA). Despite its introduction into clinical practice in the late 1950s, the worldwide very first two adverse analytical findings were registered only in 2014, being motive for an in-depth investigation of these cases. Both individuals denied the intake of the drug; however, the athletes did declare the use of the antimalarial prophylactic agent proguanil due to temporary residences in African countries. A structural similarity between chlorazanil and proguanil is given but no direct metabolic relation has been reported in the scientific literature. Moreover, chlorazanil has not been confirmed as a drug impurity of proguanil. Proguanil however is metabolized in humans to N-(4-chlorophenyl)-biguanide, which represents a chemical precursor in the synthesis of chlorazanil. In the presence of formic acid, formaldehyde, or formic acid esters, N-(4-chlorophenyl)-biguanide converts to chlorazanil. In order to probe for potential sources of the chlorazanil detected in the doping control samples, drug formulations containing proguanil and urine samples of individuals using proguanil as antimalarial drug were subjected to liquid chromatography-high resolution/high accuracy mass spectrometry. In addition, in vitro simulations with 4-chlorophenyl-biguanide and respective reactants were conducted in urine and resulting specimens analyzed for the presence of chlorazanil. While no chlorazanil was found in drug formulations, the urine samples of 2 out of 4 proguanil users returned findings for chlorazanil at low ng/mL levels, similar to the adverse analytical findings in the doping control samples. Further, in the presence of formaldehyde, formic acid and related esters, 4-chlorophenyl-biguanide was found to produce chlorazanil in human urine, suggesting that the detection of the obsolete diuretic

  3. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    OpenAIRE

    2011-01-01

    INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulate...

  4. Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis

    OpenAIRE

    2015-01-01

    Tumors require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors. Many potential oncogenic mutations have been identified in tumor angiogenesis. Somatic mutations in the small GTPase KRAS are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor activity both in vitro and...

  5. METFORMIN: A REVIEW OF THE LITERATURE

    OpenAIRE

    Rodrigues Neto, Edilson Martins; Universidade Federal do Ceará- Dep Fisiologia e Farmacologia/ Faculdade Católica Rainha do Sertão; Marques, Lidia Audrey Rocha Valadas; Universidade Federal do Ceará - Dep Clínica Odontológica; Ferreira, Maria Augusta Drago; Universidade Federal do Ceará - Dep Farmácia; Lobo, Patricia Leal Dantas; Universidade Federal do Ceará- Curso de Odontologia Campus Sobral; Girão Junior, Francisco Josimar; Faculdade Católica Rainha do Sertão; Camarão, Gisela Costa; Universidade Federal do Ceará- Dep. Fisiologia e Farmacologia; Moraes, Maria Elisabete Amaral de; Universidade Federal do Ceará- Dep. Fisiologia e Farmacologia

    2015-01-01

    Metformin, commercialized under several trademarks and also as a generic medicine, is an oral anti-diabetic drug, belonging to the biguanide class. It is actually the first choice in the treatment of Type 2 diabetes mellitus (DM2) due to its toxicity and clinical efficaciousness. It extensive use requires a constant discussion on its characteristics and applications. Current paper is a bibliographical review comprising the application of metformin in DM2 treatment as its chemical, physical-ch...

  6. Pharmacogenetics of Anti-Diabetes Drugs

    OpenAIRE

    Johanna K. DiStefano; Watanabe, Richard M

    2010-01-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment...

  7. Treatment of Acanthamoeba keratitis.

    Science.gov (United States)

    Seal, David

    2003-08-01

    The treatment of Acanthamoeba keratitis has now been possible since the first successful therapy developed in the mid 1980s with a combination of propamidine 0.1% (Brolene) and neomycin 1%. However, only half the patients responded to this regimen as the cysts were often resistant to neomycin and relatively insensitive to propamidine. This led to research for better therapy, culminating in the mid 1990s with research in Glasgow demonstrating much increased effectiveness with use of the biguanide chlorhexidine 0.02% and in London and Bristol for similar effectiveness with the polymeric polyhexamethylene biguanide (PHMB) 0.02%. Both biguanides were combined with propamidine for enhanced effectiveness but were also shown to be effective as monotherapy. While this therapy inactivates the trophozoites and cysts in Acanthamoeba keratitis in the majority of patients (approximately 90%), there have been notable failures particularly when presentation is late with deep stromal infection. Additional highly acanthamoebicidal drugs are needed that can penetrate the stroma for synergistic action. This role may be taken up by certain antineoplastic drugs, such as alkylphosphocholine-1 (Miltefosine), that also have antiprotozoal activity.

  8. Interactions and adverse reactions of metformin and other drugs%二甲双胍与其他药物的相互作用及不良反应的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙建然; 夏同佳; 许敏; 邓大同

    2016-01-01

    Biguanides are known to inhibit glycogen output,increase the use of glucose,and enhance insulin sensitivity.In practice,the biguanides also work along with insulin and other oral medications.However,when it combined with other drugs,the enzymology phar-macokinetics actions may occur.Biguanides can cause lactic acidosis,hepatotoxicity,and hypomagnesemia.This paper will give an over-view of the interactions and adverse reactions of metformin with other drugs.%双胍类药物抑制肝糖输出,增加葡萄糖的利用和胰岛素敏感性,可与其他口服降糖药及胰岛素联合降糖。但与其他药物联用时,可能发生与酶药动学相关的反应,双胍类药物可致乳酸性酸中毒、肝毒性、低镁血症。该文就二甲双胍与其他药物的相互作用及不良反应作一概述。

  9. [Evaluation of the association between the use of oral anti-hyperglycemic agents and hypoglycemia in Japan by data mining of the Japanese Adverse Drug Event Report (JADER) database].

    Science.gov (United States)

    Umetsu, Ryogo; Nishibata, Yuri; Abe, Junko; Suzuki, Yukiya; Hara, Hideaki; Nagasawa, Hideko; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2014-01-01

    Hypoglycemia due to treatment with oral anti-hyperglycemic agents (OHAs) is a major clinical problem in patients with type 2 diabetes mellitus. The aim of the present study was to evaluate the risk of hypoglycemia due to OHA use by using the Japanese Adverse Drug Event Report (JADER) database. To this end, reports of hypoglycemia events included in the JADER database between 2004 and 2012 were analyzed by calculating the reporting odds ratio (OR). The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify hypoglycemia; 254392 reports were found in the JADER database, of which 13269 were excluded because the age and sex of the patient were not reported. Finally, 241123 reports were analyzed. Among OHAs, sulfonylureas showed the highest adjusted OR (adjusted OR, 10.13; 95% confidence interval, 9.08-11.26). The adjusted ORs for meglitinides, biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were significantly lower than that of sulfonylureas. The adjusted OR of meglitinides (3.17; 95% confidence interval, 2.23-4.36) was significantly higher than that of alpha-glucosidase inhibitors or thiazolidinedione. We observed no difference between the adjusted ORs for biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors. Data mining of the JADER database was useful for analyzing OHA-associated hypoglycemia events. The results of our study suggested a low risk of hypoglycemia associated with biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors in clinical practice.

  10. Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase.

    Science.gov (United States)

    Yano, Akiko; Kubota, Masafumi; Iguchi, Kazuhiro; Usui, Shigeyuki; Hirano, Kazuyuki

    2006-05-01

    The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.

  11. Study of the relationship of TLR4 level and the blood vessel endothelial function of the GK mice%糖尿病大鼠血浆TLR4含量与血管内皮功能相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱晓莹; 李昭; 李梦; 胡健

    2014-01-01

    Objective To observe the relationship between TLR4 level and ET-1, NO of mice, in order to find the protective effect of atorvastatin and dimethyl-biguanide on blood vessel endothelial function.Methods Mice were divided into control group, experimental control group, atorvastatin group, dimethyl-biguanide group, and combination group. After five weeks, the level of ET-1, NO and TLR4 of each group were detected.Results The level of TLR4 was positively correlated with ET-1 and negatively correlated with NO.Conclusion Atorvastatin and dimethyl-biguanide may protect the blood vessel endothelial function by decreasing TLR4 level.%目的:观察大鼠TLR4含量与NO、ET-1的关系,了解阿托伐他汀和二甲双胍对血管内皮功能的保护作用。方法分组:空白对照组;实验对照组;阿托伐他汀组;二甲双胍组;联合用药组,5周后测定ET-1、NO、TLR4含量。结果各组大鼠TLR4含量与ET-1成正相关,与NO成负相关。结论阿托伐他汀和二甲双胍可能通过降低TLR4含量保护血管内皮功能。

  12. A Case Report of Successfully Treated Microsporidial Keratitis at a Tertiary Care Centre in Western India

    Directory of Open Access Journals (Sweden)

    Jagruti Jadeja

    2016-06-01

    Full Text Available A 43 year old male patient, who was initially diagnosed with chronic viral stromal keratitis but was refractory to conventional treatment, underwent a corneal biopsy on the basis of strong clinical suspicion. The biopsy revealed the presence of multiple microsporidial spores. Treatment with Polyhexamethylene Biguanide (PHMB and Chlorhexidine showed poor response. A therapeutic penetrating keratoplasty under the cover of Fluoroquinolones led to successful resolution of the infection. To our knowledge, this is the first case of microsporidial keratitis being reported from our region.

  13. A novel in vitro wound biofilm model used to evaluate low-frequency ultrasonic-assisted wound debridement

    DEFF Research Database (Denmark)

    Crone, S.; Garde, Christian; Bjarnsholt, T.

    2015-01-01

    casted in a semi-solid agar gel composed of either tryptic soy broth (TSB) or a wound simulating media (WSM; composed of Bolton broth with blood and plasma), to resemble the non-surface attached aggregates. The model was used to evaluate the antibiofilm effect of an ultrasonic-assisted wound debridement...... device (UA W) in the presence of saline irrigation and treatment with a polyhexamethylene biguanide (PHMB)-containing antiseptic. Confocal microscopy was used to evaluate the effect of treatments on biofilm disruption and cell viability counting measured the antibacterial effects. Results: Confocal...

  14. The efficacy of soft contact lens disinfection solutions against Serratia marcescens and Pseudomonas aeruginosa.

    Science.gov (United States)

    Parment, P A; Colucci, B; Nyström, B

    1996-06-01

    Samples of five different solutions for disinfection of soft contact lenses were experimentally inoculated with a strain of Pseudomonas aeruginosa or Serratia marcescens. No bacteria could be detected after one hour in solutions with biguanids, while they survived in reduced number up to 72 h in solutions with polyquaternium as active substance. However, prolonged survival after one week could not be detected. Lenses treated with polyquaternium based contact lens disinfectant solutions overnight may still harbour bacteria, which might increase the risk for bacterial complications, such as keratitis.

  15. 浅论中西药配合降糖效应

    Institute of Scientific and Technical Information of China (English)

    苗春明

    2002-01-01

    @@ 近年来,现代医学在治疗糖尿病的药物方面取得了长足进展,口服治疗糖尿病的药物已由原来的磺酰脲类(Sulfonylurea)和双胍类(Biguanide)发展到目前的α-葡糖苷酶抑制剂(α-glucosidase inhibitor)、噻唑烷二酮(Thiazolidinediones)和非磺酰类胰岛素促分泌剂等,并相继出现了第二代、第三代产品.

  16. [Oral antidiabetics of the sulfonylurea group and their problems in therapy].

    Science.gov (United States)

    Füsgen, I; Summa, J D

    1980-01-01

    By the abolition of biguanids as oral antidiabetics the importance of derivatives of sulfonylcarbamids became prominent in the treatment of diabetic elderly patients. Because of the properties of that group, there are a number of problems by the therapy with these derivatives. There is the mostly existing multimorbidity in geriatric patients with the risk of incompatibilities of drugs in cause of multitherapy and there is the influence of morbid states on the pharmacokinetics. Some of the various questions will be shortly described in this article. There are then given also practical advices for the relations with the derivatives of sulfonylcarbamids in treating diabetic patients.

  17. Review on the efficacy, safety and clinical applications of polihexanide, a modern wound antiseptic.

    Science.gov (United States)

    Hübner, N-O; Kramer, A

    2010-01-01

    Infected wounds are still one of the great challenges in medicine. In the last decade, it has become increasingly clear that antimicrobial chemotherapy is limited by the spread of antimicrobial resistance. Fortunately, new, highly effective antiseptic substances with a broad antimicrobial spectrum are available, so local treatment is expected to get increasingly more important in wound therapy. This paper reviews the antiseptic agent polihexanide (polyhexamethylene biguanide, PHMB), one of the most promising substances available today, from a clinical point of view, focusing on efficacy, safety and clinical applications.

  18. Variable evidence on metformin efficiency as weight-reducing and antiblastomogenic agent: causes and consequences

    Directory of Open Access Journals (Sweden)

    L M Berstein

    2012-06-01

    Full Text Available The growing interest to metformin in areas beyond the limits of diabetology serves as a stimulus for further evaluation of its effectiveness as a potential modulator of cancer morbidity and obesity epidemic. Gradually detectable differences in the intensity of these effects of the drug can be explained by an insufficient number of randomized trials, differences in the control groups (reference points, gender, age, pharmacogenetic and other factors, the study of which collectively promised to increase the likelihood of more favorable clinical effects of metformin and other antidiabetic biguanides in discussed areas.

  19. REDUCTION OF CARDIOVASCULAR COMPLICATIONS OF MODERN HYPOGLYCEMIC THERAPY OF DIABETES MELLITUS TYPE 2: "FLORENTINE HERESY"

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2010-01-01

    Full Text Available The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

  20. Small molecule interactions with lipid bilayers: a molecular dynamics study of chlorhexidine

    Science.gov (United States)

    van Oosten, Brad; Marquardt, Drew; Sternin, Edward; Harroun, Thad

    2013-03-01

    Chlorhexidine presents an interesting modelling challenge with a hydrophobic hexane connecting two biguanides (arginine analogues) and two aromatic rings. We conducted molecular dynamic simulations using the GROMACS simulation software to reproduce the experimental environment of chlorhexidine in a 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) bilayer to produce atomic-level information. We constructed an all-atom force field of chlorhexidine from the CHARMM36 force field using well established parameters of certain amino acids. Partial charges were treated differently, which were calculated using GAUSSIAN software. We will compare and contrast the results of our model to that of our neutron scattering experiments previously done in our lab.

  1. Drug: D00944 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 81 165.6246 D00944.gif Antidiabetic [DS:H00409] Therapeutic category: 3962 ATC code: A10BA02 biguanides AMPK... SCL47A2 [HSA:146802] map07051 Antidiabetics map04150 mTOR signaling pathway Therapeutic category of drugs i...n Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic...min D00944 Metformin hydrochloride (JP16/USP) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  2. Risk of cardiovascular disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Starup-Linde, Jakob; Scheel-Thomsen, Jan

    2014-01-01

    and biochemical parameters were collected. Logistic regression analyses were conducted and mutually adjusted for comorbidities, pharmaceutical use, and biochemical parameters. RESULTS: 10,073 DM patients were included (65,550person-years). 1947 suffered from a subsequent CE. CE prior to DM diagnosis (OR=20.18, 95......% CI: 0.54-0.72). DPP-4 inhibitors, insulin and β-cell stimulating agents had neutral effect. When results were adjusted for biochemical risk markers (1103 patients, 7271person-years, 189 cases), biguanides (OR=0.54, 95% CI: 0.34-0.87) and liraglutide (OR=0.32, 95% CI: 0.14-0.70) treatment retained...

  3. Electrospun mats from styrene/maleic anhydride copolymers: modification with amines and assessment of antimicrobial activity.

    Science.gov (United States)

    Ignatova, Milena; Stoilova, Olya; Manolova, Nevena; Markova, Nadya; Rashkov, Iliya

    2010-08-11

    New antimicrobial microfibrous electrospun mats from styrene/maleic anhydride copolymers were prepared. Two approaches were applied: (i) grafting of poly(propylene glycol) monoamine (Jeffamine® M-600) on the mats followed by formation of complex with iodine; (ii) modification of the mats with amines of 8-hydroxyquinoline or biguanide type with antimicrobial activity. Microbiological screening against S. aureus, E. coli and C. albicans revealed that both the formation of complex with iodine and the covalent attachment of 5-amino-8-hydroxyquinoline or of chlorhexidine impart high antimicrobial activity to the mats. In addition, S. aureus bacteria did not adhere to modified mats.

  4. Metformin and cancer: Technical and clinical implications for FDG-PET imaging

    Institute of Scientific and Technical Information of China (English)

    Selene; Capitanio; Cecilia; Marini; Gianmario; Sambuceti; Silvia; Morbelli

    2015-01-01

    Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seemto involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxyd-glucose positron emission tomography(FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway(the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.

  5. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

    Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  6. Riboflavin and ultraviolet-A as adjuvant treatment against Acanthamoeba cysts

    Science.gov (United States)

    Lamy, Ricardo; Chan, Elliot; Good, Samuel D; Cevallos, Vicky; Porco, Travis C; Stewart, Jay M

    2015-01-01

    Background Experimental studies have shown that the standard dose of R or R+UVA as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R+UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. Methods The log of either polyhexamethylene biguanide (PHMB) or chlorhexidine minimal cysticidal concentration (MCC) in solutions containing riboflavin (concentrations 0.1 %; 0.05% and 0.025 %) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm2 for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P-value associated with treatment. Results Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agents concentrations ≥ 200 µg/mL for Acanthamoeba castellanii samples and ≥ 100 µg/mL for Acanthamoeba polyphaga samples. There was no statistical evidence that R+UVA treatment was associated with MCC (P = 0.82). Conclusion R+UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro. PMID:26355273

  7. ASSESSMENT OF ACTION OF DISINFECTANTS AGAINST LISTERIA MONOCYTOGENES BIOFILMS

    Directory of Open Access Journals (Sweden)

    T. K. CABEÇA

    2008-12-01

    Full Text Available

    The purpose of this study was to assess the action of various disinfectants used in food industry against biofilm cells of Listeria monocytogenes formed on stainless steel surfaces during 24, 72 and 120 hours. Numbers of viable biofilm cells decreased after treatment with all the tested disinfectants (iodine, biguanide, quaternary ammonium compounds, peracetic acid and sodium hypochlorite. Sodium hypochlorite was the most effective disinfectant against the biofilm cells, while biguanide and iodine were the least. Scanning electron microscopy observations demonstrated attached cells on stainless steel surfaces after treatment with all the disinfectants. These observations showed that microorganisms were not completely removed from stainless steel surfaces after treatment with the disinfectants, however, the attachment did not means the viability of remaining cells. The biofilm age in hours (24, 72 and 120 had no apparent influence on resistance of microbiological cells to the disinfectants under study. In conclusion biofilm cells of L. monocytogenes can withstand disinfectants action.

  8. Acanthamoeba keratitis update-incidence, molecular epidemiology and new drugs for treatment.

    Science.gov (United States)

    Seal, D V

    2003-11-01

    A reliable figure for the expected incidence of Acanthamoeba keratitis of one per 30000 contact lens wearers per year has now been obtained from a combination of three cohort and three Questionnaire Reporting Surveys; 88% of cases wore hydrogel lenses and 12% wore rigid lenses. This figure now provides a basis for the expected number of cases against which to judge either epidemic outbreaks or effects of prevention with disinfecting solutions, better hygiene, or the use of disposable lenses. Molecular biology of Acanthamoeba has advanced considerably in the last 10 years with new automated sequencing technology. This has allowed the construction of a genotype identification scheme with 13 different genotypes against which to compare clinical isolates for epidemiological investigations or pathogenicity markers. So far, only four genotypes have been associated with keratitis of which the majority have been T4 but T3, T6, and T11 have each caused individual cases. Each genotype is heterogenous and can be further subdivided by comparison of sequences of diagnostic fragments of 18S rDNA, riboprinting by PCR-RFLP of 18S rDNA, or by mitochondrial DNA RFLP. Drug therapy has been revolutionised with the introduction of the biguanides-chlorhexidine or polyhexamethylene biguanide-with most but not all infections quickly resolving. Failure can still occur occasionally and further research is needed on more effective combination chemotherapy. A number of guanidines have been identified in this paper that could be usefully pursued as part of combination chemotherapy along with the alkylphosphocholines.

  9. 沿海和内地两家医院口服降糖药利用分析%Analysis on the Durg Utilization of Oral Hypoglycaemic Agents in an Inland Hospital and a Coastal Hospital

    Institute of Scientific and Technical Information of China (English)

    莫斌斌; 符成海

    2001-01-01

    To get information about the status of use of oral hypoglycaemic agents in an inland and coastal hospitals,the ordes of total cost and DDDs were employed to compare the use of oral hypoglycaemic agents in an inland hospital and a coastal hospital.Our results showed that the much less biguanides were used in the coastal hospital as compared with the inland hospital.It is conclinical practice included dimethyl biguanide,glipizide,gliclazide and glibenclamide.%目的:了解口服降糖药在沿海和内地两家医院的用药情况。方法:应用总金额排序法及用药频度(DDDs)排序法对1998~1999年沿海和内地两家医院口服降糖药的利用情况进行比较分析。结果:沿海地区使用双胍类降糖药的患者远远少于内地。结论:沿海地区肥胖型糖尿病患者少于内地。二甲双胍、格列吡嗪、格列齐特、格列本脲等目前用药活跃,仍为主要降糖药。

  10. Synthesis and pharmacological studies of aminoxy containing 2,4,6-trisubstituted-s-triazine derivatives

    Directory of Open Access Journals (Sweden)

    Jain Shilpi

    2007-01-01

    Full Text Available Arylamines on diazotization and further treatment with dicyandiamide yielded aryldicyandiamide (1a-d, which on addition with aminoxy compound (2 gave corresponding biguanides (3a-d. Cycloaddition of biguanide with ethylchloroacetate furnished 2,4,6-trisubstituted-s-triazines (4a-d. Subsequent treatment of these compounds with N-hydroxyphthalimide or N-hydroxysuccinimide in presence of triethylamine gave final compounds (5a-h. IR, 1 H NMR and mass spectra were used to confirm their structure. Compounds (5a-h were screened for antibacterial ( Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae, Pseudomonas aureus and Staphylococcus aureus and antifungal ( Candida albicans and Aspergillus fumigatus activities. Antibacterial activity revealed that compounds 5a, 5b, 5c, 5g showed comparable activity against bacteria P. vulgaris, P. aureus, where rest of the compounds showed weak activity against all the pathogenic bacteria. The fungicidal data indicated that compound 5d possess high level activity and rest of the compounds showed comparable to the standard.

  11. Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Onishi, Yukiko; Oura, Tomonori; Nishiyama, Hiroshi; Ohyama, Sumika; Takeuchi, Masakazu; Iwamoto, Noriyuki

    2016-01-01

    The efficacy and tolerability of once weekly dulaglutide 0.75 mg in Japanese patients with type 2 diabetes (T2D) were evaluated by subgroups defined by key demographic characteristics. This post hoc analysis included data from patients who received dulaglutide 0.75 mg for up to 26 weeks in three phase 3 trials (one open-label, randomized; one double-blind and open-label, randomized; one open-label, nonrandomized). Patients were classified into subgroups on the basis of sex (male, female), age (8.5%), use of concomitant sulfonylurea (yes, no), and use of concomitant biguanide (yes, no). Efficacy measures analyzed were changes from baseline in HbA1c and body weight and percentages of patients achieving HbA1c biguanides. Concomitant use of sulfonylureas had the greatest effect on the incidence of hypoglycemia. Treatment of T2D with once weekly dulaglutide 0.75 mg for 26 weeks was associated with significant improvement in glycemic control irrespective of age, sex, duration of diabetes, body weight, BMI, or concomitant medication.

  12. Metformin in the treatment of breast cancer among patients with metabolic syndrome

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    R. V. Lyubota

    2015-01-01

    Full Text Available Breast cancer (BC is one of the most common cancer among women worldwide. In 2005, the International Diabetes Federation (International Diabetes Federation declared metabolic syndrome is one of the main problems of modern medicine, as it increases the total mortality and the prevalence has reached pandemic levels. Several studies have shown that the metabolic disorders associated with metabolic syndrome, affect the carcinogenesis of BC. Improving the efficiency of chemotherapy in patients with type 2 diabetes taking biguanides compared with patients who used other hypoglycemic agents, it has become a premise for the study of the possible antitumor mechanism of action of metformin. Therefore, adequate correction of metabolic disturbances caused by metabolic syndrome may be an additional area of special treatment, as well as a measure of primary and secondary prevention of BC. Improving the efficiency of tumor therapy in patientswith type 2 diabetes taking biguanides compared with patients who used other hypoglycemic agents, it has become a prerequisite for the study of the possible antitumor mechanism of action of metformin. This paper presents the results of studying the effect of metformin on the effectiveness of neoadjuvant systemic therapy for BC patients with the metabolic syndrome.

  13. Tautomeric preferences and electron delocalization in biurets, thiobiurets, and dithiobiurets: An ab initio study

    Science.gov (United States)

    Adane, Legesse; Bharatam, Prasad V.

    In several literature reports biuret and its sulfur analogs are reported to exist in their diketo form with general formula H2N bond CX bond NH bond CY bond NH2 (X = O, Y = O, biuret; X = Y = S, dithiobiuret; and X = O, Y = S, thiobiuret). On the other hand, recently reported results on the electronic structure of biguanide analogs (X = Y = NH)demonstrated that a form equivalent to diketo is not the preferred structure. Thus, a systematic ab initio study on the tautomeric preferences of biuret and its sulfur analogs (dithiobiuret and thiobiuret) has been carried out. The results indicate that an interplay of conjugative stabilization and intramolecular hydrogen bonding to play a role in tautomeric preferences. Energy and geometric parameters, natural bond orbital analyses have been employed to understand the chemistry of the title compounds. The results indicate that unlike biguanides, these compounds prefer diketo forms containing hydrogen on the bridging nitrogen (N4) and in a trans-arrangement (1a-4a). However, tautomerization of these keto forms to the corresponding enol isomers was also found to be highly probable.

  14. Synergistic anti-cancer effect of phenformin and oxamate.

    Directory of Open Access Journals (Sweden)

    W Keith Miskimins

    Full Text Available Phenformin (phenethylbiguanide; an anti-diabetic agent plus oxamate [lactate dehydrogenase (LDH inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS. Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18F-fluorodeoxyglucose (FDG uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

  15. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Science.gov (United States)

    Shang, Fenqing; Zhang, Jiao; Li, Zhao; Zhang, Jin; Yin, Yanjun; Wang, Yaqiong; Marin, Traci L; Gongol, Brendan; Xiao, Han; Zhang, You-Yi; Chen, Zhen; Shyy, John Y-J; Lei, Ting

    2016-01-01

    Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose) polymerase 1 (PARP1). Biguanides and angiotensin II receptor blockers (ARBs) such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs), diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK) phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosyl)ation (PARylation), but increased endothelial nitric oxide synthase (eNOS) activity and silent mating type information regulation 2 homolog 1 (SIRT1) expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  16. Pharmacogenetics of Anti-Diabetes Drugs

    Directory of Open Access Journals (Sweden)

    Johanna K. DiStefano

    2010-08-01

    Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

  17. Pharmacogenetics of Anti-Diabetes Drugs.

    Science.gov (United States)

    Distefano, Johanna K; Watanabe, Richard M

    2010-08-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of 'response' can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for "individualized medicine" for patients with T2D.

  18. Biomolecular mode of action of metformin in relation to its copper binding properties.

    Science.gov (United States)

    Repiščák, Peter; Erhardt, Stefan; Rena, Graham; Paterson, Martin J

    2014-02-04

    Metformin (Metf), the most commonly used type 2 diabetes drug, is known to affect the cellular housekeeping of copper. Recently, we discovered that the structurally closely related propanediimidamide (PDI) shows a cellular behavior different from that of Metf. Here we investigate the binding of these compounds to copper, to compare their binding strength. Furthermore, we take a closer look at the electronic properties of these compounds and their copper complexes such as molecular orbital interactions and electrostatic potential surfaces. Our results clearly show that the copper binding energies cannot alone be the cause of the biochemical differentiation between Metf and PDI. We conclude that other factors such as pKa values and hydrophilicity of the compounds play a crucial role in their cellular activity. Metf in contrast to PDI can occur as an anion in aqueous medium at moderate pH, forming much stronger complexes particularly with Cu(II) ions, suggesting that biguanides but not PDI may induce easy oxidation of Cu(I) ions extracted from proteins. The higher hydrophobicity and the lack of planarity of PDI may further differentiate it from biguanides in terms of their molecular recognition characteristics. These different properties could hold the key to metformin's mitochondrial activity because they suggest that the drug could act at least in part as a pro-oxidant of accessible protein-bound Cu(I) ions.

  19. 1,5-Diarylbiguanides and their nickel(II) complexes.

    Science.gov (United States)

    McMorran, David A; McAdam, C John; van der Salm, Holly; Gordon, Keith C

    2013-02-28

    1,5-Diarylbiguanides, where the aryl groups are phenyl (HL1), 3,5-dimethylphenyl (HL2), 3,5-dimethoxyphenyl (HL3), 4-t-butylphenyl (HL4) or 4-bromophenyl (HL5), have been prepared and characterised. HL3 and HL5 have been structurally characterised by X-ray crystallography, which shows them to adopt the expected tautomeric form for biguanides. They have extensive hydrogen-bonding interactions in the solid state, involving the biguanide NH groups supported by, in the case of HL3, the OCH3 aryl substituents or, in the case of HL5, Br···Br interactions. Reactions of HL1–HL4 with Ni(BF4)2 gives complexes of the type [Ni(HL)2](BF4)2, while reactions of HL1–HL4 with Ni(BF4)2 and triethylamine give neutral complexes of the type [Ni(L)2], where the biguanide ligand has been deprotonated at the N(ring) nitrogen. Both series of complexes were characterised in solution and the solid state. Cyclic voltammetry shows a largely irreversible Ni(II)/Ni(III) oxidation which becomes easier by ca. 70 mV upon ligand deprotonation, with more subtle variations resulting from the changes in aryl ring substituents. Infrared and 1H NMR spectroscopies both provide evidence for ligand deprotonation leading to the chelate ring becoming increasingly aromatised. X-ray crystallographic analyses of five of the complexes also show changes in bond lengths and angles within the chelate ring, consistent with increased electron delocalisation. A variety of hydrogen bonding motifs involving the complex ions, counterions and solvent molecules are found. The results of DFT calculations on both cationic and neutral complexes provide calculated structures consistent with the experimental ones and these, along with the results of vibrational spectroscopic studies, provide further evidence for increased aromatisation upon deprotonation. The potential for the complexes to act as tectons for the rational assembly of hydrogen bonded metallosupramolecules is discussed and the X-ray structure of such an

  20. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones have enhanced activity under high glucose conditions

    Directory of Open Access Journals (Sweden)

    de Dios Stephanie T

    2007-10-01

    Full Text Available Abstract Background Inhibition of vascular smooth muscle cell (vSMC proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose and high (25 mM glucose increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P 3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations. The sulfonylureas chlorpropamide and gliclazide had no inhibitory effect on vSMC proliferation assessed by either [3H

  1. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  2. Metformin: A Hopeful Promise in Aging Research.

    Science.gov (United States)

    Novelle, Marta G; Ali, Ahmed; Diéguez, Carlos; Bernier, Michel; de Cabo, Rafael

    2016-03-01

    Even though the inevitable process of aging by itself cannot be considered a disease, it is directly linked to life span and is the driving force behind all age-related diseases. It is an undisputable fact that age-associated diseases are among the leading causes of death in the world, primarily in industrialized countries. During the last several years, an intensive search of antiaging treatments has led to the discovery of a variety of drugs that promote health span and/or life extension. The biguanide compound metformin is widely used for treating people with type 2 diabetes and appears to show protection against cancer, inflammation, and age-related pathologies. Here, we summarize the recent developments about metformin use in translational aging research and discuss its role as a potential geroprotector.

  3. [Acanthamoeba keratitis].

    Science.gov (United States)

    Bouheraoua, N; Labbé, A; Chaumeil, C; Liang, Q; Laroche, L; Borderie, V

    2014-10-01

    Early diagnosis and appropriate therapy are key elements for a good prognosis in Acanthamoeba keratitis (AK). AK should be considered in any case of corneal trauma complicated by exposure to soil or contaminated water, and in all contact lens (CL) wearers. A presumptive diagnosis of AK can be made clinically and with in vivo confocal microscopy, although a definitive diagnosis requires identification of Acanthamoeba on direct scraping, histology, or identification of Acanthamoeba DNA by polymerase chain reaction (PCR). We use cysticidal drugs for treating AK because encysted forms are more resistant than trophozoites to treatment. The treatment protocol used a biguanide (PHMB 0.02% or chlorhexidine 0.02%) and a diamidine (propamidine 0.1% or hexamidine 0.1%). New diagnostic modalities and more specific topical anti-amoebic treatments would substantially benefit patients with AK.

  4. Metformin: A Novel but Controversial Drug in Cancer Prevention and Treatment.

    Science.gov (United States)

    Sui, Xinbing; Xu, Yinghua; Wang, Xian; Han, Weidong; Pan, Hongming; Xiao, Mang

    2015-11-02

    Metformin, a biguanide derivative that is widely used for treating type 2 diabetes mellitus, has recently been shown to exert potential anticancer effects. Many retrospective data and laboratory studies suggest the idea that metformin has antineoplastic activity, but some other studies reach conflicting conclusions. Although the precise molecular mechanisms by which metformin affects various cancers have not been fully elucidated, activation of AMPK-dependent and AMPK-independent pathways along with energy metabolism aberration, cell cycle arrest and apoptosis or autophagy induction have emerged as crucial regulators in this process. In this Review, we describe the role of metformin in the prevention and treatment of a variety of cancers and summarize the molecular mechanisms that are currently well documented in the ability of metformin as an anticancer agent. In addition, the scientific and clinical hurdles regarding the potential role of metformin in cancer will be discussed.

  5. FORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLETS OF METFORMIN HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Shaikh T.H.

    2012-06-01

    Full Text Available Metformin HCl is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM. It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. In the present study an attempt has been made to prepare fast dissolving tablets of Metformin HCl in the oral cavity with enhanced dissolution rate. The tablets were prepared with three superdisintegrants e.g:, Croscarmellose sodium, Sodium starch glycolate and Crospovidone. The blend was examined for angle of repose, bulk density, tapped density, compressibility index and hausners ratio. The tablets were evaluated for hardenss, friability, disintegration time, dissolution rate,drug content, and were found to be within 1 min. It was concluded that the mouth dissolving tablets with proper hardness, rapidly disintegrating with enhanced dissolution can be made using selected superdisintegrants.

  6. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Taskiran, M; Toft-Nielsen, M B;

    2001-01-01

    OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted...... this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally......) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2...

  7. Gestational diabetes mellitus management with oral hypoglycemic agents.

    Science.gov (United States)

    Ryu, Rachel J; Hays, Karen E; Hebert, Mary F

    2014-12-01

    Oral hypoglycemic agents such as glyburide (second-generation sulfonylurea) and metformin (biguanide) are attractive alternatives to insulin due to lower cost, ease of administration, and better patient adherence. The majority of evidence from retrospective and prospective studies suggests comparable efficacy and safety of oral hypoglycemic agents such as glyburide and metformin as compared to insulin when used in the treatment of women with gestational diabetes mellitus (GDM). Glyburide and metformin have altered pharmacokinetics during pregnancy and both agents cross the placenta. In this article, we review the efficacy, safety, and dosage of oral hypoglycemic agents for the treatment of gestational diabetes mellitus. Additional research is needed to evaluate optimal dosage for glyburide and metformin during pregnancy. Comparative studies evaluating the effects of glyburide and metformin on long-term maternal and fetal outcomes are also needed.

  8. Raman microspectroscopy analysis in the treatment of acanthamoeba keratitis.

    Science.gov (United States)

    Rusciano, Giulia; Capriglione, Paola; Pesce, Giuseppe; Del Prete, Salvatore; Cennamo, Gilda; Di Cave, David; Cerulli, Luciano; Sasso, Antonio

    2013-01-01

    Acanthamoeba keratitis is a rare but serious corneal disease, often observed in contact lens wearers. Clinical treatment of infected patients frequently involves the use of polyhexamethylene biguanide (PHMB), a polymer used as a disinfectant and antiseptic, which is toxic also for the epithelial cells of the cornea. Prompt and effective diagnostic tools are hence highly desiderable for both starting early therapy and timely suspension of the treatment. In this work we use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in cystic phase. In particular, we investigate the effect of PHMB at the single-cell level, providing useful information on both the underlying biochemical mechanism and the time frame for Acanthamoeba eradication in ocular infections. Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard multivariate analysis methods, allows discriminating between live and dead Acanthamoebas, which is fundamental to optimizing patients' treatment.

  9. Modulation of P2 receptors on pancreatic β-cells by agonists and antagonists: a molecular target for type 2 diabetes treatment.

    Science.gov (United States)

    Pacheco, Paulo Anastácio Furtado; Ferreira, Leonardo Gomes Braga; Alves, Luiz Anastacio; Faria, Robson Xavier

    2013-05-01

    Morbidity and mortality from diabetes mellitus (DM) are serious worldwide concerns. By the year 2030, the estimated number of diabetic patients will reach a staggering 439 million worldwide. Diabetes mellitus type 2 (DM2), which involves disturbances in both insulin secretion and resistance, is the most common form of diabetes and affects approximately 5 to 7% of the world's population. When a patient with DM2 cannot regulate his or her blood glucose levels through diet, weight loss, or exercise, oral medications, such as hypoglycemic agents (i.e., sulphonylureas, biguanides, alpha glucosidase inhibitors and thiazolidinediones), are crucial. Here, we discuss some physiological aspects of P2 receptors on pancreatic β-cells, which express a variety of P2 receptor isoforms. These receptors enhance glucose-dependent insulin release. In addition, we speculate on the potential of purinergic compounds as novel or additional treatments for Type 2 Diabetes mellitus.

  10. Antimocrobial Polymer

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, William F. (Utica, OH); Huang, Zhi-Heng (Walnut Creek, CA); Wright, Stacy C. (Columbus, GA)

    2005-09-06

    A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A)3P wherein A is hydroxyalkyl; and the antimicrobial agent is chlorhexidine, dimethylchlorophenol, cetyl pyridinium chloride, gentian violet, triclosan, thymol, iodine, and mixtures thereof.

  11. Cobalamin Deficiency in Elderly Patients: A Personal View

    Directory of Open Access Journals (Sweden)

    Emmanuel Andrès

    2008-01-01

    Full Text Available Cobalamin (vitamin B12 deficiency is particularly common in the elderly (>65 years of age but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

  12. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

    DEFF Research Database (Denmark)

    Chindera, Kantaraja; Mahato, Manohar; Sharma, Ashwani Kumar

    2016-01-01

    To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption...... by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when...... to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance....

  13. Raman microspectroscopy analysis in the treatment of acanthamoeba keratitis.

    Directory of Open Access Journals (Sweden)

    Giulia Rusciano

    Full Text Available Acanthamoeba keratitis is a rare but serious corneal disease, often observed in contact lens wearers. Clinical treatment of infected patients frequently involves the use of polyhexamethylene biguanide (PHMB, a polymer used as a disinfectant and antiseptic, which is toxic also for the epithelial cells of the cornea. Prompt and effective diagnostic tools are hence highly desiderable for both starting early therapy and timely suspension of the treatment. In this work we use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in cystic phase. In particular, we investigate the effect of PHMB at the single-cell level, providing useful information on both the underlying biochemical mechanism and the time frame for Acanthamoeba eradication in ocular infections. Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard multivariate analysis methods, allows discriminating between live and dead Acanthamoebas, which is fundamental to optimizing patients' treatment.

  14. Radial keratoneuritis as a presenting sign in Acanthamoeba keratitis

    Directory of Open Access Journals (Sweden)

    Abdullah Alfawaz

    2011-01-01

    Full Text Available The visual outcomes of Acanthamoeba keratitis, a rare cause of corneal infection, can be devastating. This paper reports two contact lens wearers with severe pain and photophobia who presented to the emergency room. Biomicroscopy revealed radial keratoneuritis in both individuals. Tissue culture on a nonnutrient agar plate with Escherichia coli overlay resulted in a heavy growth of Acanthamoeba. The inpatient treatment included 0.02% polyhexamethylene biguanide, chlorhexidine, neomycin/polymyxin B/bacitracin (Neosporin, and oral fluconazole, which successfully controlled the corneal infection and improvement in the best corrected visual acuity in both patients. Infection did not recur during the 12-month follow-up period. Acanthamoeba keratitis can present as radial keratoneuritis, mimicking other common corneal infections resulting in diagnostic and treatment delays. Early diagnosis and prudent treatment of Acanthamoeba keratitis are the keys to restoring vision and avoiding the subsequent need for penetrating keratoplasty.

  15. Progress in Antibacterial Finishing Agents for Textiles%纺织品抗菌整理剂研究进展

    Institute of Scientific and Technical Information of China (English)

    陈仕国; 郭玉娟; 陈少军; 戈早川

    2012-01-01

    综述了纺织品抗菌整理剂的分类以及纳米银、二氧化钛、季铵盐化合物、聚六亚甲基双胍、三氯新、卤胺化合物及壳聚糖等抗菌剂的作用机理及其优缺点,并阐述了纺织品抗菌剂的理想特征和未来发展趋势.%The most recent developments in antimicrobial treatments of textiles using various active agents from the antimicrobial classification, and antibacterial mechanism, such as nano-silver, nano titanium dioxide, quaternary ammonium salts, polyhexamethylene biguanide, triclosan, regenerable N-halamine compounds and chitosan, are reviewed. The advantages and disadvantages, ideal characteristics and development trends of the antimicrobial textiles are also illustrated.

  16. SGLT 2 Inhibitors: A New Therapeutic Target And Its Role In Current Clinical Practice

    Directory of Open Access Journals (Sweden)

    PV Shiji

    2015-10-01

    Full Text Available Diabetes, one of the major life style diseases, is associated with high morbidity and mortality owing to its microvascular and macrovascular complications. The chance of development of various complications can be effectively prevented by tight glycemic control. We have various groups of drugs like Biguanides, Sulfonyl ureas, Glitazones, Alpha-glucosidase inhibitors, Incretin based therapy, Insulin and Insulin analogues in the armamentarium to treat diabetes. But still, the number of patients attaining glycemic targets are relatively low and various adverse effect limit the use of some of these drugs, especially in special groups. Hence there is ongoing research to develop newer and newer drugs which provide sustained blood glucose reduction with minimal adverse effects. SGLT-2 inhibitors are a new group of drugs recently approved by FDA to treat Diabetes. In this review we discuss about mechanism of action, various adverse effects and the clinical role of various SGLT-2 Inhibitors.

  17. Application de la tectonique moleculaire a des systemes auto-assembles non cristallins a l'aide des diarylbiguanides et des diarylaminotriazines

    Science.gov (United States)

    Lebel, Olivier

    Supramolecular chemistry seeks to exploit non-covalent interactions strategically to modulate the properties of compounds. Molecular tectonics, which is a branch of supramolecular chemistry developed in the Wuest group, involves the design of novel ordered materials through self-assembly. Although until now molecular tectonics has only been used to generate porous crystalline materials, it would be in principle possible to translate the principles of molecular tectonics to less-ordered materials such as liquid crystals, gels or amorphous materials. The studies described in this thesis aim to use the knowledge acquired in the course of exploring molecular tectonics during the last fifteen years to develop compounds that are capable of self-association but favor the formation of gels or amorphous solids rather than crystals. Towards this goal, we have used 1,5-diarylbiguanides as synthetic precursors. Since these compounds are poorly known, we have first sought to establish simple procedures for their synthesis and characterization. We have also studied the crystal structures of parent compound 1,5-diphenylbiguanide and its hydrochloride salt. In order to assess the potential of biguanides and their salts as sticky sites in molecular tectonics, we have then studied the crystallographic structures of 1,3- and 1,4-phenylenebis(biguanide) and their salts in order to confirm the presence of recurring and general recognition motifs. These studies have demonstrated that even though biguanides show certain preferences in their self-assembly patterns, their flexibility and their large number of hydrogen-bonding sites limit the predictability of these patterns. In the second part of this work, we discuss the use of sodium salts of 4,6-diarylamino-1,3,5-triazine-2-carboxylates as low-molecular-weight gelators. These compounds associate in a unidimensional fashion to form fibres. The fibres in turn form three-dimensional networks that can gel DMSO at very low concentration. We

  18. Charge transfer adducts of metal complexes of π-donor ligands with I 2 and TCNQ

    Science.gov (United States)

    Bera, T. R.; Sen, D.; Ghosh, R.

    1989-01-01

    Copper(II) and nickel(II) biguanides and O-alkyl-1-amidinourea can act as donors for the formation of charge transfer (CT) adducts with I 2 and tetracyanoquinodimethane (TNCQ) as acceptors. Iodine adducts are characterized both in solid and solution states whereas TCNQ adducts obtain only in solution. Appearance of a broad band at 355 nm for iodine adducts and at 335 nm for TNCQ adducts and shifting of i.r. frequencies support the formation of donor acceptor associates. Elemental analysis establishes 1:1 stoichiometry of the solid adducts. The K and ɛ values determined by modified Benesi—Hildebrand, Scott and Rose—Drago equations are found to be of the order of 10 4 and 10 3 respectively at 298 K in methanol. The solvent effect on the K values is discussed in terms of coupled solute-solute and solute-solvent equilibria.

  19. Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment.

    Science.gov (United States)

    Wang, Jia; Xia, Shi'an; Zhu, Zhizhen

    2015-03-01

    Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is more potent than metformin. However its potential application as a anti-cancer regent is far behind metformin. In order to investigate any beneficial effect of combination of Phenformin and radiotherapy, non-small cell lung cancer cell lines A549 and H1299 were exposure under different dose of ionizing radiation with or without Phenformin. Results indicated Phenformin showed synergistic effect and could induce more cancer cell apoptosis and inhibition of tumor growth compared with ionizing radiation alone. Furthermore, this synergistic effect may be through different pathway according to cancer cell genotype background. Our results showed Phenformin induced AMPK activation in A549 but not H1299. However, Phenformin activated eIF2α in both cell lines. Our findings implicated Phenformin may be used as radiosensitizer for non-small cell lung cancer therapy.

  20. Newer Approaches In The Treatment of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Kamlesh Patel

    2013-01-01

    Full Text Available Diabetes Mellitus is a public health problem worldwide. The most effective anti-diabetic drugs currently available include insulin and newer insulin preparations, sulphonylureas, biguanides, meglitinides, thiazolidinediones, alpha- glucosidase inhibitors, incretins, guargum and glucomannan. However, the future therapies will need to focus on those patents who do not respond well to these treatments and who account for 50% of the health care costs of diabetes mellitus. Drug development for diabetes mellitus has been directed at improving currently available drugs and findings new compounds. In this review article, we will review the role of future new chemical entities able to target the metabolic disorder. Some of these new anti-diabetic treatment strategies may in the future not only control symptoms and modify the natural course of diabetes, but also potentially prevent or cure the disease.

  1. Curing Kinetics and Thermal Stability of Diglycidyl Ether of Bisphenol-A Using Mixtures of Heterocyclic Derivatives of Stannanes and 4,4'-Diaminodiphenylsulfone

    Institute of Scientific and Technical Information of China (English)

    SINGH Vikram; DEEP Gagan; NARULA Anudeep Kumar

    2008-01-01

    Curing kinetics of diglycidyl ether of bisphenol-A (DGEBA) in the presence of varying molar ratios of derivafives of stannanes to 4,4'-diaminodiphenylsulfone (DDS) was investigated by the dynamic differential scanning calorimetry. The derivatives were synthesized by reacting 1 mole of biguanide (B) with 1 mole of phenylethyltindihydride (PETH) or phenylmethyltindihydride (PMTH) or phenylbutyltindihydride (PBTH) and designated as BPETH or BPMTH or BPBTH respectively. These derivatives were characterized by elemental analysis and spectroscopic techniques such as IR, 1H NMR, 13C NMR and 119Sn NMR. The mixtures of these derivatives to DDS at of epoxy resins. The thermal stability of the isothermally cured resins was also evaluated using dynamic thermogravimetry in a nitrogen atmosphere.

  2. 瑞格列奈二甲双胍片中乙醇残留量的测定%Determination of repaglinide metformin tablets ethanol residues

    Institute of Scientific and Technical Information of China (English)

    刘芳; 张丽娟; 王建平

    2014-01-01

    瑞格列奈是一种非磺酰脲类促胰岛素分泌剂,盐酸二甲双胍是一种双胍类的降血糖药,其组成的固定复方降血糖药,治疗单独应用瑞格列奈或盐酸二甲双胍不能有效控制血糖或者已经服用瑞格列奈和盐酸二甲双胍治疗的2型糖尿病患者。%repaglinide is a non-sulfonylurea insulin secretagogue, a biguanide is metformin hydrochloride hypoglycemic agents, consisting of a fixed combination of hypoglycemic agents, the treatment of repaglinide or metformin hydrochloride alone can not effectively control blood sugar or already taking repaglinide and metformin hydrochloride treatment of type 2 diabetes.

  3. Controlling sulfate reducing bacteria by slug dosing with quick-kill antimicrobials and by continuous dosing with isothiazolones

    Energy Technology Data Exchange (ETDEWEB)

    Haack, T.K.; Greenley, D.E.

    1991-06-25

    This patent describes a process for controlling biological contamination of oil production water injection systems by sulfate-reducing sessile bacteria wherein a slug dose of a quick-kill antimicrobial selected from one or more of the group consisting of (C{sub 3}-C{sub 7}) alkanedials, formaldehyde, cationic polymeric biguanides, quaternary ammonium compounds (alkyldimethylbenzylammonium chlorides), quarternary phosphodium compounds, phenolics, cocodiamine, 2-bromo-2-nitropropanediol, acrolein, dibromonitrilopropionamide and organic thiocyanates is applied to the injection water, the improvement comprising substantially continuously dosing the injection water at a concentration of about 0.25 to 5 ppm based on the weight of injection water with a maintenance antimicrobial selected from the group consisting of an isothiazolone.

  4. LOW LEVELS OF SERUM CYANOCOBALAMIN IN A METFORMIN-TREATED PATIENT. CASE REPORT AND COMPARISON WITH LITERATURE DATA.

    Science.gov (United States)

    Strugaru, Anca-Monica; Botnariu, Gina; Tuchiluş, Cristina; Anisie, Ecaterina; Agoroaei, Luminiţa; Grigoriu, Ioana-Cezara; Butnaru, Elena

    2016-01-01

    Metformin is a widely used oral antidiabetic biguanide compound. According to the literature, metformin may lower the serum cyanocobalamin levels. We present the case of a 71-old-male treated with metformin for 15 years. When presenting to a periodic checkup, low serum cyanocobalamin levels where found. Laboratory tests showed levels below normal range for hemoglobin (12.7 g/dL) and hematocrit (37.8%). After patient reevaluation, a change in antidiabetic treatment will be considered if metformin will be found the cause of low serum cyanocobalamin levels. Other cases reported in the literature support this hypothesis, justifying the study of the influence of metformin therapy on serum vitamin B12 levels in patients diagnosed with diabetes. The influence of patient age, metformin dosage, duration of treatment and time since diabetes diagnosis on serum levels of vitamin B12 also need to be determined.

  5. Pattern of antidiabetic drugs use in type-2 diabetic patients in a medicine outpatient clinic of a tertiary care teaching hospital

    Directory of Open Access Journals (Sweden)

    Bela Patel

    2013-08-01

    Full Text Available Background: Diabetes mellitus (DM is an important public health problem in developing countries. Drug utilisation study of antidiabetic agents is of paramount importance to promote rational drug use in diabetics and make available valuable information for the healthcare team. The aim of study was to investigate the drug utilization pattern in type-2 diabetic patients. Methods: A prospective, cross-sectional study was carried out in medicine outpatient clinic of tertiary care hospital, Ahmedabad for eight weeks. Patients with type-2 diabetes and on drug therapy for at least one month were included. Patients’ socio-demographic and clinical data were noted in a pre-designed proforma. Data was analysed by using SPSS version 20 and Excel 2007. Results: Total 114 patients were enrolled with mean (± standard deviation age and duration of diabetes of 56.8 ± 10.5 and 8.3 ± 9.4 years respectively. Male: Female ratio was 0.72:1. Mean fasting and postprandial blood glucose levels were 147.5 ± 73.1 and 215.6 ± 97.3 mg/dl respectively. Most common symptom was weakness/fatigue (77.2%. Hypertension (70.2% was most common co-morbid illness. Mean number of drugs prescribed were 7.8 ± 2.5. Total numbers of patients receiving more than five drugs were 89.5%. Most commonly used drug group was biguanides (87.7% followed by sulphonylureas (68.4%. Conclusion: Metformin (biguanide was the most utilized (87.7% antidiabetic drug for type-2 diabetes. This study revealed that the pattern of antidiabetic prescription was rational and largely compliant with NICE (National Institute for Health and Clinical Excellence guidelines. [Int J Basic Clin Pharmacol 2013; 2(4.000: 485-491

  6. Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data.

    Science.gov (United States)

    Rhee, Connie M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

    2017-01-01

    Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time.

  7. Acanthamoeba encystment: multifactorial effects of buffers, biocides, and demulcents present in contact lens care solutions

    Directory of Open Access Journals (Sweden)

    Kovacs CJ

    2015-10-01

    Full Text Available Christopher J Kovacs, Shawn C Lynch, Marjorie J Rah, Kimberly A Millard, Timothy W Morris Bausch & Lomb Incorporated, Rochester, NY, USA Purpose: To determine whether agents which are purportedly capable of inducing encystment of Acanthamoeba can recapitulate the signal when tested in differing formulations. Methods: In accordance with the International Standard ISO 19045, Acanthamoeba castellanii ATCC 50370 trophozoites were cultured in antibiotic-free axenic medium, treated with test solutions, and encystment rates plus viability were measured via bright field and fluorescent microscopy. Test solutions included phosphate-buffered saline (PBS, borate-buffered saline, biguanide- and hydrogen peroxide (H2O2-based biocides, propylene glycol (PG and povidone (POV ophthalmic demulcents, and one-step H2O2-based contact lens disinfection systems. Results: Only PBS solutions with 0.25 ppm polyaminopropyl biguanide (PAPB and increasing concentrations of PG and POV stimulated A. castellanii encystment in a dose-dependent manner, whereas PBS solutions containing 3% H2O2 and increasing concentrations of PG and POV did not stimulate encystment. Borate-buffered saline and PBS/citrate solutions containing PG also did not stimulate encystment. In addition, no encystment was observed after 24 hours, 7 days, or 14 days of exposures of trophozoites to one-step H2O2 contact lens disinfection products or related solutions. Conclusion: The lack of any encystment observed when trophozoites were treated with existing or new one-step H2O2 contact lens care products, as well as when trophozoites were exposed to various related test solutions, confirms that Acanthamoeba encystment is a complex process which depends upon simultaneous contributions of multiple factors including buffers, biocides, and demulcents. Keywords: propylene glycol, contact lens care system, hydrogen peroxide disinfecting solution

  8. Metformin-associated lactic acidosis: Current perspectives on causes and risk.

    Science.gov (United States)

    DeFronzo, Ralph; Fleming, G Alexander; Chen, Kim; Bicsak, Thomas A

    2016-02-01

    Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

  9. The inhibition of monoamine oxidase by phenformin and pentamidine.

    Science.gov (United States)

    Barkhuizen, M; Petzer, A; Petzer, J P

    2014-09-01

    A computational study has suggested that phenformin, an oral hypoglycaemic drug, may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The present study therefore investigates the MAO inhibitory properties of phenformin. Pentamidine, a structurally related diamidine compound, has previously been reported to be a MAO inhibitor and was included in this study as a reference compound. Using recombinant human MAO-A and MAO-B, this study finds that phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50 value of 41 µM. Pentamidine, on the other hand, potently inhibits both MAO-A and MAO-B with IC50 values of 0.61 μM and 0.22 μM, respectively. An examination of the recoveries of the enzymatic activities after dilution and dialysis of the enzyme-inhibitor complexes shows that both compounds interact reversibly with the MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive inhibitor with estimated Ki values of 0.41 μM and 0.22 μM for the inhibition of MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of MAO-A inhibition with an estimated Ki value of 65 µM. This study concludes that biguanide and amidine functional groups are most likely important structural features for the inhibition of the MAOs by phenformin and pentamidine, and compounds containing these and closely related functional groups should be considered as potential MAO inhibitors. Furthermore, the biguanide and amidine functional groups may act as useful moieties in the future design of MAO inhibitors.

  10. ROLE FAILURE CORRECTION OF 25(OHD IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME

    Directory of Open Access Journals (Sweden)

    M. V. Matveyeva

    2015-01-01

    Full Text Available Objective. To estimate the correction failure 25 (OH D in patients with polycystic ovary syndrome.Material and Methods. The study involved 44 patients with polycystic ovary syndrome, aged 31.32 ± 5.05, who were randomly assigned to 2 groups: 1st – obtained coca biguanides and Kolekaltsiferol, second – combined oral contraceptive (combined hormonal and biguanides. The comparison group consisted of 22 healthy women matched for age and sex. Polycystic Ovarian Syndrome (PCOS was verified on theОригинальные статьиБюллетень сибирской медицины, 2015, том 14, № 5, с. 47–53 53basis of diagnostic criteria ESHRE / ASRM (2012. 25 (OH vitamin D was determined by enzyme-linked immunosorbent assay (ELISA ng/ml. Examined glucose and fasting insulin, HOMA index of insulin re-sistance. Depression was assessed using the Beck test. Statistical analysis – R-system.Results. The patients with PCOS defined by the expression deficit of 25 (OH D, which is associated with hyperandrogenism, hyperglycemia, hyperinsulinemia, insulin resistance, as well as depression. Ad-mission kolekaltsiferola leads to improved glucose metabolism and manifestations of PCOS, and also significantly reduces the parameters of OT, OT / OB, depression.Conclusion. Failure correction of 25 (OH D contributes to the improvement of metabolic and psycho-logical parameters of fertility.

  11. Antitumor mechanisms of metformin: Signaling, metabolism, immunity and beyond

    Directory of Open Access Journals (Sweden)

    Ismael Samudio

    2010-08-01

    Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.

  12. Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype.

    Science.gov (United States)

    Cuyàs, Elisabet; Fernández-Arroyo, Salvador; Corominas-Faja, Bruna; Rodríguez-Gallego, Esther; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; De Llorens, Rafael; Joven, Jorge; Menendez, Javier A

    2015-05-20

    Metabolic flexibility might be particularly constrained in tumors bearing mutations in isocitrate dehydrogenase 1 (IDH1) leading to the production of the oncometabolite 2-hydroxygluratate (2HG). To test the hypothesis that IDH1 mutations could generate metabolic vulnerabilities for therapeutic intervention, we utilized an MCF10A cell line engineered with an arginine-to-histidine conversion at position 132 (R132H) in the catalytic site of IDH1, which equips the enzyme with a neomorphic α-ketoglutarate to 2HG reducing activity in an otherwise isogenic background. IDH1 R132H/+ and isogenic IDH1 +/+ parental cells were screened for their ability to generate energy-rich NADH when cultured in a standardized high-throughput Phenotype MicroArrayplatform comprising >300 nutrients. A radical remodeling of the metabotype occurred in cells carrying the R132H mutation since they presented a markedly altered ability to utilize numerous carbon catabolic fuels. A mitochondria toxicity-screening modality confirmed a severe inability of IDH1-mutated cells to use various carbon substrates that are fed into the electron transport chain at different points. The mitochondrial biguanide poisons, metformin and phenformin, further impaired the intrinsic weakness of IDH1-mutant cells to use certain carbon-energy sources. Additionally, metabolic reprogramming of IDH1-mutant cells increased their sensitivity to metformin in assays of cell proliferation, clonogenic potential, and mammosphere formation. Targeted metabolomics studies revealed that the ability of metformin to interfere with the anaplerotic entry of glutamine into the tricarboxylic acid cycle could explain the hypersensitivity of IDH1-mutant cells to biguanides. Moreover, synergistic interactions occurred when metformin treatment was combined with the selective R132H-IDH1 inhibitor AGI-5198. Together, these results suggest that therapy involving the simultaneous targeting of metabolic vulnerabilities with metformin, and 2HG

  13. 社区医院2008~2010年口服降糖药物应用分析%Analysis of oral hypoglycemic drug use in community hospitals: 2008 ~ 2010

    Institute of Scientific and Technical Information of China (English)

    赵大贵; 杜伟

    2011-01-01

    目的 分析社区医院口服降糖药的应用特点和发展趋势,为临床合理用药提供参考.方法对宜宾市南岸文化广场社区卫生服务中心2008~2010年口服降糖药应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行回顾性分析.结果 3年口服降糖药销售金额占抗糖尿病药总金额80%以上;销售金额、DDDs排序前3位的依次是:双胍类、磺酰脲类、餐时血糖调节剂;3年中,二甲双胍缓释片、格列吡嗪缓释片、瑞格列奈位列单品种销售金额前3位;噻唑烷二酮类DDC最高,二甲双胍缓释片、格列吡嗪缓释片DDC较低,在使用上占主导地位.结论社区口服降糖药用药较合理,双胍类、磺酰脲类、餐时血糖调节剂的应用,与社区医院药物治疗糖尿病策略是相符的.%Objective To analyze retrospectively the status quo and tendency of oral hypoglycemic drug use in community hospitals,and provide basis for rational drug use. Methods The article analyzed statistically oral hypoglycemic drugs used during the period of 2008 ~ 2010 in respect of varieties, sales amount,drug daily dosages (DDDS) and defined daily consumption ( DDC). Results The sales amount of oral hypoglycemic drug accounted for more than 80% of the total sales amount of antidiabetic for three successive years. The top three oral hypoglycemic drugs according to sales amount and DDDS were Biguanide,sulfonylurea and prandial glucose regulator. The top three oral hypoglycemic drugs according to sale of single-species were Biguanide,Glipizide Sustained-Release Tablets and Repaglinide. The DDC of thiazolidinediones was the highest,and those of Glipizide Sustained-Release Tablets and Repaglinide were lower,which became the most frequently used drugs in clinic. Conclusion The study shows that the utilization of oral hypoglycemic a-gents in community hospitals is basically rational. Biguanide, sulfonylurea and prandial glucose regulator are used in the way

  14. 1294张口服降糖药处方分析%Analysis of 1294 prescriptions of oral hypoglycemic agents

    Institute of Scientific and Technical Information of China (English)

    谢雅君; 吴久鸿; 王杰松; 薛克昌; 许樟荣

    2011-01-01

    Objective: To investigate the utilization of oral hypoglycemic agents in outpatient in our hospital and provide reference for clinical medication. Methods: The prescriptions of oral hypoglycemic agents in outpatient in January 2010 were retrospectively analyzed, in respect of the numbers of prescriptions, recipe quantity and drug combination. The DDDs and DUI were analyzed. Results: Oral hypoglycemic agents used with high frequency were biguanide (54.87%), sulfonylurea (34.47%) and α -glycosidase inhibitor (34.47%). Metformin and acarbose were used most. The DUI of 16 drugs was close to 1 among 20 oral hypoglycemic agents. The proportion of combined oral hypoglycemic agents accounted for 45.98% in all prescriptions. The most common combination use of oral hypoglycemic agents were biguanide and sulfonylurea, sulfonylurea and α -glycosidase inhibitor. Conclusion: The utilization of oral hypoglycemic agents in outpatient of our hospital was reasonable.%目的:了解我院门诊口服降糖药的使用情况,为临床用药提供参考.方法:回顾性分析我院门诊2010年1月份的口服降糖药处方,对处方数、处方量和联合用药等进行统计,并计算用药频度(DDDs)和药物利用指数(DUI).结果:使用频次较多的降糖药分别是双胍类(54.87%)、磺酰脲类(34.47%)和α-葡萄糖苷酶抑制剂(34.47%);格华止和拜唐苹是处方量最多的药物品种;20种口服降糖药中,有16种药物的DUI值接近1;口服降糖药联合应用占总处方数的45.98%,最常见为磺酰脲类+双胍类和磺酰脲类+α-葡萄糖苷酶抑制剂.结论:我院门诊使用降糖药物基本合理.

  15. Risk Factor Analysis for Lactic Acidosis%乳酸性酸中毒的危险因素分析

    Institute of Scientific and Technical Information of China (English)

    舒英; 佘宁兰; 龚蓉; 刘蔓莉; 徐争鸣; 王平; 陈泽君; 程弓

    2011-01-01

    Objective To analyze the risk factors of lactic acidosis. Methods The clinical data of 32 patients with lactic acidosis admitted to our hospital from May 2008 to December 2010 were studied retrospectively. Results All patients had type 2 diabetes mellitus. Among them, 27 (84. 6%) were older than 60, 20 (62. 5%) had ingested antidiabetic drugs of biguanides, 12 (37. 5%) were complicated by pulmonary diseases, 9 (28. 1%) by heart diseases, 15 (46. 9%) by renal dysfunction, and 8 (25. 0%) by liver dysfunction. Conclusions Diabetes mellitus, old age, ingesting of biguanides, cardiopulmonary diseases, renal and hepatic dysfunction all contribute to the occurrence of lactic acidosis. During clinical work, we should try to avoid the above-mentioned risk factors.%目的 分析乳酸性酸中毒发生的危险因素,警示临床工作.方法 回顾性分析2008年5月-2010年12月收治的32例乳酸性酸中毒患者的临床资料.结果 32例患者均合并2型糖尿病,其中老年患者27例(占84.6%);20例有服用双胍类降糖药物史(占62.5%);12例合并肺部疾病(占37.5%);9例合并心脏疾病(占28.1%);15例合并肾功能不全(占46.9%);8例合并肝功能异常(占25.0%).结论 糖尿病、老年、使用双胍类药物、合并心肺疾病及肝肾功能不全都是发生乳酸性酸中毒的危险因素.在临床工作中,对高危患者需提高警惕,尽量避免危险因素叠加以减少乳酸性酸中毒的发生.

  16. 上海市同济医院2011-2014年口服降糖药物使用情况分析%Utilization of oral hypoglycemic agents in Tongji hospital of Shanghai during 2011-2014

    Institute of Scientific and Technical Information of China (English)

    叶显撑; 张玉臣; 祝德秋

    2016-01-01

    The utilization of oral hypoglycemic agents (OHAs) in Shanghai Tongji Hospital during 2011-2014 was statistically analyzed in respect of consumption sum, DDDs, and DDC so as to provide references for clinical medication. There were various categories of OHAs in our hospital. The consumption sum of OHAs showed an upward trend, yet the proportion of the consumption sum of OHAs in the consumption sum of hypoglycemic agents and the total drug consumption sum showed a downward trend. The top 3 of OHAs were a-glycosidase inhibitors, sulfonylureas and biguanides in the list of consumption and sulfonylureas, biguanides and a-glycosidase inhibitors in the list of DDDs, respectively. Metformin occupied the ifrst place in the list of DDDs. The use of OHAs is basically rational with various categories of OHAs.%本文对上海市同济医院2011—2014年口服降糖药物(OHAs)的用药金额、用药频度、日用药金额等进行统计分析,为临床合理用药提供参考。4年来上海市同济医院OHAs品种全面,使用金额呈上升趋势,但OHAs占降糖药使用金额比例、OHAs占全部用药金额比例均处于微降趋势。a-糖苷酶抑制剂、磺脲类、双胍类4年来稳居销售金额排名1~3位;DDDs排序中,磺脲类、双胍类、a-糖苷酶抑制剂稳居1~3位。二甲双胍位列单品种DDDs排序的首位。上海市同济医院2011—2014年OHAs的临床使用基本合理,药物种类全面。

  17. Arterial stiffness, as monitored by cardio–ankle vascular index, is affected by obstructive sleep apnea, blood glucose control, and body weight – a case with 8 years follow up

    Directory of Open Access Journals (Sweden)

    Shimizu K

    2016-08-01

    Full Text Available Kazuhiro Shimizu,1 Tomoyuki Yamamoto,2,3 Kohji Shirai2,4 1Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan; 2Department of Vascular Function, Toho University Sakura Medical Center, Chiba, Japan; 3Biological Information Analysis Section, Fukuda Denshi Co., Ltd., Tokyo, Japan; 4Department of Internal Medicine, Mihama Hospital, Chiba, Japan Abstract: The cardio–ankle vascular index (CAVI is an indicator of arterial stiffness from the heart to the ankles. The CAVI increases as arteriosclerosis progresses, but it can be decreased by appropriate treatment. There are several risk factors for coronary artery disease, however, the degree of stress caused by each separate risk factor to arteries cannot be assessed. CAVI increases with age and according to the severity of atherosclerosis. We found that CAVI also changes in response to the control of risk factors, which may be associated with the functional stiffness of arteries. CAVI can be a useful indicator of risk control for coronary artery disease. We followed a patient aged 71 years who had diabetes mellitus and obstructive sleep apnea (OSA by measuring CAVI for 8 years from age 63. He underwent coronary artery bypass grafting due to angina pectoris when he was 63 years old. Before coronary artery bypass grafting, CAVI was 11.8 on the right and 11.5 on the left. Three years later he was found to have OSA and received treatment with continuous positive airway pressure. There was a marked improvement in CAVI after continuous positive airway pressure (age 68; right 10.4, left 10.2. However, following a gradual increase in body weight and worsening of diabetes mellitus, CAVI showed an increasing trend. CAVI decreased with biguanides treatment, but increased again with an increase in body weight. In conclusion, CAVI responded to the patient’s conditions including obesity, diabetes mellitus, and OSA. CAVI is not only a marker of arterial stiffness, but can also be a

  18. Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype

    Science.gov (United States)

    Cuyàs, Elisabet; Fernández-Arroyo, Salvador; Corominas-Faja, Bruna; Rodríguez-Gallego, Esther; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; De Llorens, Rafael; Joven, Jorge; Menendez, Javier A.

    2015-01-01

    Metabolic flexibility might be particularly constrained in tumors bearing mutations in isocitrate dehydrogenase 1 (IDH1) leading to the production of the oncometabolite 2-hydroxygluratate (2HG). To test the hypothesis that IDH1 mutations could generate metabolic vulnerabilities for therapeutic intervention, we utilized an MCF10A cell line engineered with an arginine-to-histidine conversion at position 132 (R132H) in the catalytic site of IDH1, which equips the enzyme with a neomorphic α-ketoglutarate to 2HG reducing activity in an otherwise isogenic background. IDH1 R132H/+ and isogenic IDH1 +/+ parental cells were screened for their ability to generate energy-rich NADH when cultured in a standardized high-throughput Phenotype MicroArrayplatform comprising >300 nutrients. A radical remodeling of the metabotype occurred in cells carrying the R132H mutation since they presented a markedly altered ability to utilize numerous carbon catabolic fuels. A mitochondria toxicity-screening modality confirmed a severe inability of IDH1-mutated cells to use various carbon substrates that are fed into the electron transport chain at different points. The mitochondrial biguanide poisons, metformin and phenformin, further impaired the intrinsic weakness of IDH1-mutant cells to use certain carbon-energy sources. Additionally, metabolic reprogramming of IDH1-mutant cells increased their sensitivity to metformin in assays of cell proliferation, clonogenic potential, and mammosphere formation. Targeted metabolomics studies revealed that the ability of metformin to interfere with the anaplerotic entry of glutamine into the tricarboxylic acid cycle could explain the hypersensitivity of IDH1-mutant cells to biguanides. Moreover, synergistic interactions occurred when metformin treatment was combined with the selective R132H-IDH1 inhibitor AGI-5198. Together, these results suggest that therapy involving the simultaneous targeting of metabolic vulnerabilities with metformin, and 2HG

  19. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes.

    Science.gov (United States)

    Huang, Yi; Greene, Eriko; Murray Stewart, Tracy; Goodwin, Andrew C; Baylin, Stephen B; Woster, Patrick M; Casero, Robert A

    2007-05-08

    Epigenetic chromatin modification is a major regulator of eukaryotic gene expression, and aberrant epigenetic silencing of gene expression contributes to tumorigenesis. Histone modifications include acetylation, phosphorylation, and methylation, resulting in a combination of histone marks known collectively as the histone code. The chromatin marks at a given promoter determine, in part, whether specific promoters are in an open/active conformation or closed/repressed conformation. Dimethyl-lysine 4 histone H3 (H3K4me2) is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by the lysine-specific demethylase 1 (LSD1), a homologue of polyamine oxidases, may broadly repress gene expression. We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. Furthermore, we demonstrate by chromatin immunoprecipitation analysis that the reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. We thus define important new agents for reversing aberrant repression of gene transcription.

  20. Low Molecular Weight Amidoximes that Act as Potent Inhibitors of Lysine-Specific Demethylase 1

    Science.gov (United States)

    Hazeldine, Stuart; Pachaiyappan, Boobalan; Steinbergs, Nora; Nowotarski, Shannon; Hanson, Allison S.; Casero, Robert A.; Woster, Patrick M.

    2012-01-01

    The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides and their urea- and thiourea isosteres are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1, but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD) and transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents. PMID:22876979

  1. New poly(ester urea) derived from L-leucine: electrospun scaffolds loaded with antibacterial drugs and enzymes.

    Science.gov (United States)

    Díaz, Angélica; del Valle, Luis J; Tugushi, David; Katsarava, Ramaz; Puiggalí, Jordi

    2015-01-01

    Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising materials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol-diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibroblast and epithelial cells.

  2. The Prelude on Novel Receptor and Ligand Targets Involved in the Treatment of Diabetes Mellitus

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    Venu Gopal Jonnalagadda

    2014-05-01

    Full Text Available Metabolic disorders are a group of disorders, due to the disruption of the normal metabolic process at a cellular level. Diabetes Mellitus and Tyrosinaemia are the majorly reported metabolic disorders. Among them, Diabetes Mellitus is a one of the leading metabolic syndrome, affecting 5 to 7 % of the population worldwide and mainly characterised by elevated levels of glucose and is associated with two types of physiological event disturbances such as impaired insulin secretion and insulin resistance. Up to now, various treatment strategies are like insulin, alphaglucosidase inhibitors, biguanides, incretins were being followed. Concurrently, various novel therapeutic strategies are required to advance the therapy of Diabetes mellitus. For the last few decades, there has been an extensive research in understanding the metabolic pathways involved in Diabetes Mellitus at the cellular level and having the profound knowledge on cell-growth, cell-cycle, and apoptosis at a molecular level provides new targets for the treatment of Diabetes Mellitus. Receptor signalling has been involved in these mechanisms, to translate the information coming from outside. To understand the various receptors involved in these pathways, we must have a sound knowledge on receptors and ligands involved in it. This review mainly summarises the receptors and ligands which are involved the Diabetes Mellitus. Finally, researchers have to develop the alternative chemical moieties that retain their affinity to receptors and efficacy. Diabetes Mellitus being a metabolic disorder due to the glucose surfeit, demands the need for regular exercise along with dietary changes.

  3. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    Science.gov (United States)

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.

  4. High Pressure Laminates with Antimicrobial Properties

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    Sandra Magina

    2016-02-01

    Full Text Available High-pressure laminates (HPLs are durable, resistant to environmental effects and good cost-benefit decorative surface composite materials with special properties tailored to meet market demand. In the present work, polyhexamethylene biguanide (PHMB was incorporated for the first time into melamine-formaldehyde resin (MF matrix on the outer layer of HPLs to provide them antimicrobial properties. Chemical binding of PHMB to resin matrix was detected on the surface of produced HPLs by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR. Antimicrobial evaluation tests were carried out on the ensuing HPLs doped with PHMB against gram-positive Listeria innocua and gram-negative Escherichia coli bacteria. The results revealed that laminates prepared with 1.0 wt % PHMB in MF resin were bacteriostatic (i.e., inhibited the growth of microorganisms, whereas those prepared with 2.4 wt % PHMB in MF resin exhibited bactericidal activity (i.e., inactivated the inoculated microorganisms. The results herein reported disclose a promising strategy for the production of HPLs with antimicrobial activity without affecting basic intrinsic quality parameters of composite material.

  5. Antimicrobial activity of different disinfectants against cariogenic microorganisms

    Directory of Open Access Journals (Sweden)

    Esra UZER CELIK

    Full Text Available Abstract The aim of this study was to assess the in vitro antimicrobial effects of chlorhexidine digluconate (CHX, polyhexamethylene biguanide (PHBM, and octenidine dihydrochloride (OCT on cariogenic microorganisms by using their minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC. CHX, PHBM, and OCT were diluted in distilled water to the final test concentrations. Using the in-tube dilution method, Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Actinomyces viscosus were cultivated on blood agar and Mueller–Hinton broth (MHB at 37°C for 48 h. They were read using a spectrophotometer to detect MIC. To determine MBC, samples in the range of the turbidity threshold after 24 h were transferred onto blood agar and evaluated for growth after 24 h. Different MICs and MBCs were observed in all disinfectants against each microorganism. The lowest MIC and MBC against S. mutans (60 mg/L were obtained from PHBM. The lowest values against L. rhamnosus (15 mg/L, 30 mg/L, A. viscosus (30 mg/L, and L. acidophilus (15 mg/L, 30 mg/L were determined by OCT. PHBM and OCT have the potential to be replaced with CHX because they were effective against cariogenic microorganisms.

  6. Prospective, non-interventional, uncontrolled, open-chart, pharmacoepidemiologic study of prescribing patterns for anti-diabetic drugs at tertiary care hospital in Erode

    Directory of Open Access Journals (Sweden)

    Radhika P

    2009-01-01

    Full Text Available The aim of this study is to determine current prescribing patterns for anti-diabetic drugs adopted by physicians in Erode. The prospective, non interventional, uncontrolled, open-chart, pharmacoepidemiological study was conducted from January -2007 to April -2007 at a diabetic care centre having 350 diabetic patients. The pattern of prescribing anti-diabetic drugs was recorded along with glycosylated haemoglobin levels, total cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein and triglycerides in insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus patients and the values were observed. The prescribing pattern of the oral anti-diabetic drugs shows that out of the various oral anti-diabetic drugs′ available, drugs from only two groups were prescribed. Sulphonylureas, biguanides and combination therapy accounts for 31.43%, 20.28% and 33.71% of prescriptions, respectively, while insulin alone and with OAD′s accounts for 6.28% and 8.29% prescriptions, respectively. Overall, prescribing trend is away from monotherapy with insulin and sulphonylureas and towards combination therapies.

  7. Pharmacogenetic studies update in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Shalini; Singh; Kauser; Usman; Monisha; Banerjee

    2016-01-01

    Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.

  8. The advances in the treatment of fungal keratitis%真菌性角膜炎治疗进展

    Institute of Scientific and Technical Information of China (English)

    刘欣; 曾庆延

    2015-01-01

    真菌性角膜炎是一种严重的致盲性眼病,近年来治疗真菌性角膜炎新的药物有四代唑类、聚六甲基双胍、钙调磷酸酶抑制剂等,新药物剂型有凝胶缓释剂、克霉唑-β-环糊精等,新的手术方式有角膜胶原交联术、准分子激光治疗性角膜切削术、深板层角膜移植术等.%Fungal keratitis is a serious blindness leading disease.In recent years, new treatment included new medicines such as fourth generation azoles, poly hexamethylene biguanide, calcineurin inhibitors, and new dosage forms such as mucoadhesive gels and Clotrimazole-β-Cyclodextrin, new operation such as corneal collagen cross-linking, excimer laser phototherapeutic keratectomy, deep lamellar keratoplasty,etc.

  9. Serotonin stimulates lateral habenula via activation of the post-synaptic serotonin 2/3 receptors and transient receptor potential channels.

    Science.gov (United States)

    Zuo, Wanhong; Zhang, Yong; Xie, Guiqin; Gregor, Danielle; Bekker, Alex; Ye, Jiang-Hong

    2016-02-01

    There is growing interest on the role of the lateral habenula (LHb) in depression, because it closely and bilaterally connects with the serotoninergic raphe nuclei. The LHb sends glutamate efferents to the raphe nuclei, while it receives serotoninergic afferents, and expresses a high density of serotonin (5-HT) receptors. Recent studies suggest that 5-HT receptors exist both in the presynaptic and postsynaptic sites of LHb neurons, and activation of these receptors may have different effects on the activity of LHb neurons. The current study focused on the effect of 5-HT on the postsynaptic membrane. We found that 5-HT initiated a depolarizing inward current (I((5-HTi))) and accelerated spontaneous firing in ∼80% of LHb neurons in rat brain slices. I((5-HTi)) was also induced by the 5-HT uptake blocker citalopram, indicating activity of endogenous 5-HT. I((5-HTi)) was diminished by 5-HT(2/3) receptor antagonists (ritanserin, SB-200646 or ondansetron), and activated by the selective 5-HT(2/3) agonists 1-(3-Chlorophenyl) piperazine hydrochloride or 1-(3-Chlorophenyl) biguanide hydrochloride. Furthermore, I((5-HTi)) was attenuated by 2-Aminoethyl diphenylborinate, a blocker of transient receptor potential channels, and an IP3 receptor inhibitor, indicating the involvement of transient receptor potential channels. These results demonstrate that the reciprocal connection between the LHb and the 5-HT system highlights a key role for 5-HT stimulation of LHb neurons that may be important in the pathogenesis of depression.

  10. Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Xinbing Sui

    Full Text Available Colorectal cancer (CRC is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.

  11. Impact of Serum Retinol-Binding Protein 4 Levels on Regulation of Remnant-Like Particles Triglyceride in Type 2 Diabetes Mellitus

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    Naoto Yamaaki

    2013-01-01

    Full Text Available Background. Although retinol-binding protein 4 (RBP4 associates with insulin resistance and remnant-like particles triglyceride (RLP-TG elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM male patients (age years, body mass index (BMI  kg/m2, waist circumference (WC  cm, and HbA1c (NGSP %. Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA and subcutaneous fat area (SFA were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG ( and , TG ( and , RLP-TG/TG ( and , and age ( and , although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R. Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG ( but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM.

  12. [Adjunctive therapies to glycaemic control of type 1 diabetes mellitus].

    Science.gov (United States)

    Gabbay, Mônica de A Lima

    2008-03-01

    Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1%, lowering postprandial blood glucose levels and decreasing daily insulin doses.

  13. Treatment update: thiazolidinediones in combination with metformin for the treatment of type 2 diabetes

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    John M Stafford

    2007-10-01

    Full Text Available John M Stafford1, Tom Elasy21Division of Diabetes Endocrinology and Metabolism, Vanderbilt University; 2Vanderbilt Eskind Diabetes Clinic, Vanderbilt University Medical CenterAbstract: Type 2 diabetes mellitus (DM2 is characterized by excessive hepatic gluconeogenesis, increased insulin resistance and a progressive inability of pancreatic beta cells to produce sufficient insulin. DM2 evolves as a progression from normal glucose tolerance, to impaired glucose tolerance (IGT to frank diabetes mellitus, reflecting the establishment of insulin resistance and beta cell dysfunction. Insulin resistance not only contributes to impaired glycemic control in DM2, but to the development of hypertension, dyslipidemia and endothelial dysfunction. Cardiovascular disease is the primary morbidity for patients with DM2. The onset of insulin resistance and cardiovascular insult likely occurs well before the onset of IGT is detected clinically. Biguanides and thiazolidinediones (TZDs are two classes of oral agents for the management of DM2 that improve insulin resistance, and thus have potential cardiovascular benefits beyond glycemic control alone. Metformin additionally inhibits hepatic gluconeogenesis. The combined use of two of these agents targets key pathophysiologic defects in DM2. Single pill combinations of rosiglitazone/metformin and pioglitazone/metformin have recently been approved for use in the US and Europe. This article reviews the clinical data behind the use of metformin in combination with TZDs for the management of diabetes, its impact on vascular health, side effects and potential mechanisms of action for combined use.Keywords: thiazolidinediones; metformin; Type 2 diabetes

  14. Treatment update: thiazolidinediones in combination with metformin for the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    John M Stafford

    2007-09-01

    Full Text Available John M Stafford1, Tom Elasy21Division of Diabetes Endocrinology and Metabolism, Vanderbilt University; 2Vanderbilt Eskind Diabetes Clinic, Vanderbilt University Medical CenterAbstract: Type 2 diabetes mellitus (DM2 is characterized by excessive hepatic gluconeogenesis, increased insulin resistance and a progressive inability of pancreatic beta cells to produce sufficient insulin. DM2 evolves as a progression from normal glucose tolerance, to impaired glucose tolerance (IGT to frank diabetes mellitus, reflecting the establishment of insulin resistance and beta cell dysfunction. Insulin resistance not only contributes to impaired glycemic control in DM2, but to the development of hypertension, dyslipidemia and endothelial dysfunction. Cardiovascular disease is the primary morbidity for patients with DM2. The onset of insulin resistance and cardiovascular insult likely occurs well before the onset of IGT is detected clinically. Biguanides and thiazolidinediones (TZDs are two classes of oral agents for the management of DM2 that improve insulin resistance, and thus have potential cardiovascular benefits beyond glycemic control alone. Metformin additionally inhibits hepatic gluconeogenesis. The combined use of two of these agents targets key pathophysiologic defects in DM2. Single pill combinations of rosiglitazone/metformin and pioglitazone/metformin have recently been approved for use in the US and Europe. This article reviews the clinical data behind the use of metformin in combination with TZDs for the management of diabetes, its impact on vascular health, side effects and potential mechanisms of action for combined use.Keywords: thiazolidinediones; metformin; Type 2 diabetes

  15. Cost analysis study of oral antidiabetic drugs available in Indian market

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    Nisharani B Jadhav, Manisha S Bhosale, Charles V Adhav

    2013-01-01

    Full Text Available There exists a wide range of variation in the prices of drugs marketed in India and other countries of the world. Very few studies have been conducted to reveal such price variations in the open market. Aim & Objectives: To evaluate the cost of oral anti-diabetics of different generic classes and different brand names of one compound, To evaluate the difference in cost of different brands for the same active drug by calculating percentage variation of cost. Methods: Cost of a particular drug being manufactured by different companies, in the same strength, number and dosage form was compared. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and the percentage variation in price was calculated. Results: In Single drug therapy, among sulfonylurea group of drugs, Glimepiride (1 mg shows maximum price variation of 655.38%, while Glipizide (10mg shows variation of 38.88%. In Biguanides & Thizolidinediones groups of drugs, Metformin (500 mg & Pioglitazone (15 mg show maximum price variation of 308.33% & 542% respectively. In α-glucosidases inhibitor group of drugs, Miglitol shows maximum price variation of 135.50 %. In combination therapies, Glipizide & Metformin combination shows the maximum variation up to 399.04 %. Conclusion: The average percentage price variation of different brands of the same drug manufactured in India is very wide and the appraisal and management of marketing drugs should be directed toward maximizing the benefits of therapy and minimizing negative personal and economic consequences

  16. Energy disruptors: rising stars in anticancer therapy?

    Science.gov (United States)

    Bost, F; Decoux-Poullot, A-G; Tanti, J F; Clavel, S

    2016-01-01

    The metabolic features of tumor cells diverge from those of normal cells. Otto Warburg was the first to observe that cancer cells dramatically increase their glucose consumption to generate ATP. He also claimed that cancer cells do not have functional mitochondria or oxidative phosphorylation (OXPHOS) but simply rely on glycolysis to provide ATP to the cell, even in the presence of oxygen (aerobic glycolysis). Several studies have revisited this observation and demonstrated that most cancer cells contain metabolically efficient mitochondria. Indeed, to sustain high proliferation rates, cancer cells require functional mitochondria to provide ATP and intermediate metabolites, such as citrate and cofactors, for anabolic reactions. This difference in metabolism between normal and tumors cells causes the latter to be more sensitive to agents that can disrupt energy homeostasis. In this review, we focus on energy disruptors, such as biguanides, 2-deoxyglucose and 5-aminoimidazole-4-carboxamide ribonucleotide, that interfere with the main metabolic pathways of the cells, OXPHOS, glycolysis and glutamine metabolism. We discuss the preclinical data and the mechanisms of action of these disruptors at the cellular and molecular levels. Finally, we consider whether these drugs can reasonably contribute to the antitumoral therapeutic arsenal in the future. PMID:26779810

  17. Presumed late recurrence of Acanthamoeba keratitis exacerbated by exposure to topical corticosteroids

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    Dipika V Patel

    2013-01-01

    Full Text Available A 28-year-old female with a history of contact lens wear presented with a 1 week history of pain and photophobia in her left eye. In vivo confocal microscopy (IVCM and corneal scrape confirmed the diagnosis of Acanthamoeba keratitis (AK which was treated with intensive topical propamidine isethionate (0.1% and chlorhexidine (0.02% with tapering dosage over 11 months. Five years after complete resolution of AK and cessation of all contact lens wear, the subject presented to her optometrist with a history of ocular discomfort and mild photophobia. Without further investigation she was prescribed topical corticosteroids. Three weeks later she presented with pain and reduced vision in the left eye. Slit-lamp examination revealed focal, inferior corneal stromal edema. IVCM confirmed widespread Acanthamoeba cysts. Treatment with topical polyhexamethylene biguanide (PHMB 0.02% and propamidine isethionate 0.1% resulted in resolution of the AK. Despite an initially mild AK, this subject presumably retained viable Acanthamoeba cysts in her cornea 5 years after the initial episode. This report highlights the importance of caution when using corticosteroids in patients with a previous history of AK, even in the relatively distant past. Patients with AK should be warned regarding the risks of recurrence following presumed resolution.

  18. Relationship between Legionella pneumophila and Acanthamoeba polyphaga: Physiological status and susceptibility to chemical inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Barker, J.; Farrell, I. (Aston Univ., Aston Triangle, Birmingham (United Kingdom)); Brown, M.R.W.; Collier, P.J.; Gilbert, P. (Univ. of Manchester (United Kingdom))

    1992-08-01

    Survival studies were conducted on Legionella pneumophila cells that had been grown intracellulary in Acanthamoeba polyphaga and then exposed to polyhexamethylene biguanide (PHMB), benzisothiazolone (BIT), and 5-chloro-N-methylisothiazolone (CMIT). Susceptibilities were also determined for L. pneumophila grown under iron-sufficient and iron-depleted conditions. BIT was relatively ineffective against cells to PHMB and CMIT. The activities of all three biocides were greatly reduced against L. pneumophila grown in amoebae. PHMB (1 [times] MIC) gave 99.99% reductions in viability for cultures grown in broth within 6 h and no detectable survivors at 24 h but only 90 and 99.9% killing at 6 h and 24 h, respectively, for cells grown in amoebae. The antimicrobial properties of the three biocides against A. polyphaga were also determined. The majority of amoebae recovered from BIT treatment, but few, if any, survived CMIT treatment or exposure of PHMB. This study not only shows the profound effect that intra-amoebal growth has on the physiological status and antimicrobial susceptibility of L. pneumophila but also reveals PHMB to be a potential biocide for effective water treatment. In this respect, PHMB has significant activity, below its recommended use concentrations, against both the host amoeba and L. pneumophila.

  19. Use of multiple immunosuppressive agents in recalcitrant ACANTHAMOEBA scleritis.

    Science.gov (United States)

    Igras, Estera; Murphy, Conor

    2015-04-15

    A 48-year-old woman who is a contact lens wearer presented with unilateral ACANTHAMOEBA keratitis, confirmed by PCR, which responded initially to topical polyhexamethylene biguanide (PHMB) and brolene. Three months later, despite continued treatment, she developed diffuse anterior scleritis with severe pain and marked scleral injection but without evidence of recurrence keratitis. Oral non-steroidal anti-inflammatories and oral high-dose corticosteroids were added without success. Subsequent treatment with intravenous methylprednisolone and high-dose cyclosporine led to a temporary improvement. Re-presenting with signs of recurrent scleritis and severe pain, the antitumor necrosis factor monoclonal antibody adalimumab, and later oral cyclophosphamide, were added. This led to complete quiescence of the scleritis. Unfortunately, frequent recurrences of ACANTHAMOEBA keratitis and anterior uveitis occurred on immunosuppression requiring continued treatment with PHMB, brolene and topical corticosteroids. This is the first case of severe refractory ACANTHAMOEBA scleritis requiring the concomitant use of four immunosuppressive agents to achieve continued disease control. The challenges in managing this case are discussed.

  20. Autophagy inhibitors as a potential antiamoebic treatment for Acanthamoeba keratitis.

    Science.gov (United States)

    Moon, Eun-Kyung; Kim, So-Hee; Hong, Yeonchul; Chung, Dong-Il; Goo, Youn-Kyoung; Kong, Hyun-Hee

    2015-07-01

    Acanthamoeba cysts are resistant to extreme physical and chemical conditions. Autophagy is an essential pathway for encystation of Acanthamoeba cells. To evaluate the possibility of an autophagic Acanthamoeba encystation mechanism, we evaluated autophagy inhibitors, such as 3-methyladenine (3MA), LY294002, wortmannin, bafilomycin A, and chloroquine. Among these autophagy inhibitors, the use of 3MA and chloroquine showed a significant reduction in the encystation ratio in Acanthamoeba cells. Wortmannin also inhibited the formation of mature cysts, while LY294002 and bafilomycin A did not affect the encystation of Acanthamoeba cells. Transmission electron microscopy revealed that 3MA and wortmannin inhibited autophagy formation and that chloroquine interfered with the formation of autolysosomes. Inhibition of autophagy or autolysosome formation resulted in a significant block in the encystation in Acanthamoeba cells. Clinical treatment with 0.02% polyhexamethylene biguanide (PHMB) showed high cytopathic effects on Acanthamoeba trophozoites and cysts; however, it also revealed high cytopathic effects on human corneal epithelial cells. In this study, we investigated effects of the combination of a low (0.00125%) concentration of PHMB with each of the autophagy inhibitors 3MA, wortmannin, and chloroquine on Acanthamoeba and human corneal epithelial cells. These new combination treatments showed low cytopathic effects on human corneal cells and high cytopathic effects on Acanthamoeba cells. Taken together, these results provide fundamental information for optimizing the treatment of Acanthamoeba keratitis.

  1. Managing type 2 diabetes: balancing HbA1c and body weight.

    Science.gov (United States)

    Mavian, Annie A; Miller, Stephan; Henry, Robert R

    2010-05-01

    Most patients with type 2 diabetes present with comorbid overweight or obesity. Reaching and maintaining acceptable glycemic control is more difficult in overweight and obese patients, and these conditions are associated with increased risk for cardiovascular and other diseases. Glycemic management for these patients is complicated by the fact that insulin and many of the oral medications available to treat type 2 diabetes produce additional weight gain. However, an increasing number of therapeutic options are available that are weight neutral or lead to weight loss in addition to their glycemic benefits. This article evaluates the evidence from clinical trials regarding the relative glycemic benefits, measured in terms of glycated hemoglobin change, versus the impact on body weight of each medication currently approved for type 2 diabetes. In general, the sulfonylureas, thiazolidinediones, and D-phenylalanine derivatives have been shown to promote weight gain. The dipeptidyl peptidase-4 inhibitors are weight neutral, while the biguanides, incretin mimetics, and amylin mimetics promote weight loss. Trials examining the glycemic benefits of the weight loss agents orlistat and sibutramine are also examined. Awareness of this evidence base can be used to inform medication selection in support of weight management goals for patients with type 2 diabetes.

  2. Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).

    Science.gov (United States)

    Liang, Xiaomin; Chien, Huan-Chieh; Yee, Sook Wah; Giacomini, Marilyn M; Chen, Eugene C; Piao, Meiling; Hao, Jia; Twelves, Jolyn; Lepist, Eve-Irene; Ray, Adrian S; Giacomini, Kathleen M

    2015-12-07

    The biguanide metformin is widely used as first-line therapy for the treatment of type 2 diabetes. Predominately a cation at physiological pH's, metformin is transported by membrane transporters, which play major roles in its absorption and disposition. Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3). Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 ± 0.2 mM) and other cationic compounds (MPP(+) and famotidine). The uptake mechanism for hTHTR-2 was pH and electrochemical gradient sensitive. Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin. Species differences in the substrate specificity of THTR-2 between human and mouse orthologues were observed. Taken together, our data suggest that hTHTR-2 may play a role in the intestinal absorption and tissue distribution of metformin and other organic cations and that the transporter may be a target for drug-drug and drug-nutrient interactions.

  3. Spectroscopic and molecular modelling studies of binding mechanism of metformin with bovine serum albumin

    Science.gov (United States)

    Sharma, Deepti; Ojha, Himanshu; Pathak, Mallika; Singh, Bhawna; Sharma, Navneet; Singh, Anju; Kakkar, Rita; Sharma, Rakesh K.

    2016-08-01

    Metformin is a biguanide class of drug used for the treatment of diabetes mellitus. It is well known that serum protein-ligand binding interaction significantly influence the biodistribution of a drug. Current study was performed to characterize the binding mechanism of metformin with serum albumin. The binding interaction of the metformin with bovine serum albumin (BSA) was examined using UV-Vis absorption spectroscopy, fluorescence, circular dichroism, density functional theory and molecular docking studies. Absorption spectra and fluorescence emission spectra pointed out the weak binding of metformin with BSA as was apparent from the slight change in absorbance and fluorescence intensity of BSA in presence of metformin. Circular dichroism study implied the significant change in the conformation of BSA upon binding with metformin. Density functional theory calculations showed that metformin has non-planar geometry and has two energy states. The docking studies evidently signified that metformin could bind significantly to the three binding sites in BSA via hydrophobic, hydrogen bonding and electrostatic interactions. The data suggested the existence of non-covalent specific binding interaction in the complexation of metformin with BSA. The present study will certainly contribute to the development of metformin as a therapeutic molecule.

  4. Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2α) pathway protect ovarian cancer cells from metformin-induced apoptosis.

    Science.gov (United States)

    Moon, Hee-Sun; Kim, Boyun; Gwak, HyeRan; Suh, Dong Hoon; Song, Yong Sang

    2016-04-01

    Metformin, an oral biguanide for the treatment of type II diabetes, has been shown to have anticancer effects in ovarian cancer. Energy starvation induced by metformin causes endoplasmic reticulum stress-mediated unfolded protein response (UPR) and autophagy. UPR and autophagy act as a survival or death mechanism in cells. In this study, we observed that metformin-induced apoptosis was relieved by autophagy and the PERK/eIF2α pathway in ovarian cancer cells, but not in peripheral blood mononuclear cells (PBMC) or 'normal' ovarian surface epithelial cells (OSE). Increased PARP cleavage and increased LC3B-II with ATG5-ATG12 complex suggested the induction of apoptosis and autophagy, respectively, in metformin-treated ovarian cancer cells. Accumulation of acidic vacuoles in the cytoplasm and downregulation of p62 further supported late-stage autophagy. Interestingly, metformin induced interdependent activation between autophagy and the UPR, especially the PERK/eIF2α pathway. Inhibition of autophagy-induced PERK inhibition, and vice versa, were demonstrated using small molecular inhibitors (PERK inhibitor I, GSK2606414; autophagy inhibitor, 3-MA, and BafA1). Moreover, autophagy and PERK activation protected ovarian cancer cells against metformin-induced apoptosis. Metformin treatment in the presence of inhibitors of PERK and autophagy, however, had no cytotoxic effects on OSE or PBMC. In conclusion, these results suggest that inhibition of autophagy and PERK can enhance the selective anticancer effects of metformin on ovarian cancer cells. © 2015 Wiley Periodicals, Inc.

  5. Antimicrobial mouthrinse use as an adjunct method in peri-implant biofilm control

    Directory of Open Access Journals (Sweden)

    Vinicius PEDRAZZI

    2014-01-01

    Full Text Available Great possibilities for oral rehabilitation emerged as a result of scientific consolidation, as well as a large number of dental implant applications. Along with implants appeared diseases such as mucositis and peri-implantitis, requiring management through several strategies applied at different stages. Biofilm accumulation is associated with clinical signs manifest by both tooth and implant inflammation. With this in mind, regular and complete biofilm elimination becomes essential for disease prevention and host protection. Chemical control of biofilms, as an adjuvant to mechanical oral hygiene, is fully justified by its simplicity and efficacy proven by studies based on clinical evidence. The purpose of this review was to present a consensus regarding the importance of antimicrobial mouthrinse use as an auxiliary method in chemical peri-implant biofilm control. The active ingredients of the several available mouthrinses include bis-biguanide, essential oils, phenols, quaternary ammonium compounds, oxygenating compounds, chlorine derivatives, plant extracts, fluorides, antibiotics and antimicrobial agent combinations. It was concluded that there is strong clinical evidence that at least two mouthrinses have scientifically proven efficacy against different oral biofilms, i.e., chlorhexidine digluconate and essential oils; however, 0.12% chlorhexidine digluconate presents a number of unwanted side effects and should be prescribed with caution. Chemical agents seem beneficial in controlling peri-implant inflammation, although they require further investigation. We recommend a scientifically proven antiseptic, with significant short and long term efficacy and with no unwanted side effects, for the prevention and/or treatment of peri-implant disease.

  6. Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics.

    Science.gov (United States)

    Arkwright, Richard T; Deshmukh, Rahul; Adapa, Nikhil; Stevens, Ryan; Zonder, Emily; Zhang, Zhongyu; Farshi, Pershang; Ahmed, Reda Saber Ibrahim; El-Banna, Hossny Awad; Chan, Tak-Hang; Dou, Q Ping

    2015-01-01

    Adenosine Monophosphate-Activated Protein Kinase or AMPK is a highly-conserved master-regulator of numerous cellular processes, including: Maintaining cellular-energy homeostasis, modulation of cytoskeletaldynamics, directing cell growth-rates and influencing cell-death pathways. AMPK has recently emerged as a promising molecular target in cancer therapy. In fact, AMPK deficiencies have been shown to enhance cell growth and proliferation, which is consistent with enhancement of tumorigenesis by AMPK-loss. Conversely, activation of AMPK is associated with tumor growth suppression via inhibition of the Mammalian Target of Rapamycin Complex-1 (mTORC1) or the mTOR signal pathway. The scientific communities' recognition that AMPK-activating compounds possess an anti-neoplastic effect has contributed to a rush of discoveries and developments in AMPK-activating compounds as potential anticancer-drugs. One such example is the class of compounds known as Biguanides, which include Metformin and Phenformin. The current review will showcase natural compounds and their derivatives that activate the AMPK-complex and signaling pathway. In addition, the biology and history of AMPK-signaling and AMPK-activating compounds will be overviewed, their anticancer-roles and mechanisms-of-actions will be discussed, and potential strategies for the development of novel, selective AMPK-activators with enhanced efficacy and reduced toxicity will be proposed.

  7. Systemic injection of p-chloroamphetamine eliminates the effect of the 5-HT3 compounds on learning.

    Science.gov (United States)

    Hong, E; Meneses, A

    1996-04-01

    There is evidence that 5-HT3 antagonists enhance learning and memory; however, their mechanisms of action are unknown. The aim of the present work was to investigate further the role of 5-HT3 receptors involved in learning, using the specific 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (mCPBG) and the 5-HT3 antagonists ondansetron and tropisetron. p-Chloroamphetamine (PCA) pretreatment was used to determine whether pre- or postsynaptic 5-HT3 receptors are involved in learning. The posttraining intraperitoneal (IP) injection of each drug was analyzed on a lever-press response on autoshaping, which is an associative learning task. The results showed that mCPBG impaired retention of the conditioned response (CR), whereas tropisetron and ondansetron improved it. In other animals, PCA alone did not affect CR but was able to block the effects of the 5-HT3 ligands. The present data suggest that the actions of 5-HT3 compounds could be due to their interaction with presynaptic 5-HT3 receptors.

  8. Biofilms of Enterococcus faecalis and Enterococcus faecium isolated from the processing of ricotta and the control of these pathogens through cleaning and sanitization procedures.

    Science.gov (United States)

    da Silva Fernandes, Meg; Kabuki, Dirce Yorika; Kuaye, Arnaldo Yoshiteru

    2015-05-04

    The biofilm formation of Enterococcus faecalis and Enterococcus faecium isolated from the processing of ricotta on stainless steel coupons was evaluated, and the effect of cleaning and sanitization procedures in the control of these biofilms was determined. The formation of biofilms was observed while varying the incubation temperature (7, 25 and 39°C) and time (0, 1, 2, 4, 6 and 8 days). At 7°C, the counts of E. faecalis and E. faecium were below 2 log10 CFU/cm(2). For the temperatures of 25 and 39°C, after 1 day, the counts of E. faecalis and E. faecium were 5.75 and 6.07 log10 CFU/cm(2), respectively, which is characteristic of biofilm formation. The tested sanitation procedures a) acid-anionic tensioactive cleaning, b) anionic tensioactive cleaning+sanitizer and c) acid-anionic tensioactive cleaning+sanitizer were effective in removing the biofilms, reducing the counts to levels below 0.4 log10 CFU/cm(2). The sanitizer biguanide was the least effective, and peracetic acid was the most effective. These studies revealed the ability of enterococci to form biofilms and the importance of the cleaning step and the type of sanitizer used in sanitation processes for the effective removal of biofilms.

  9. Inhibition of the anti-staphylococcal activity of the antiseptic polihexanide by mucin.

    Science.gov (United States)

    Ansorg, Rainer; Rath, Peter-Michael; Fabry, Werner

    2003-01-01

    The antiseptic Lavasept (LS), containing the polymeric biguanide polihexanide (CAS 28757-48-4), possesses microbicidal activity against a broad spectrum of bacteria including Staphylococcus aureus. It is used for antiseptic wound care in concentrations corresponding to 0.2-0.4 mg polihexanide per ml. To obtain basic data on its ability to eradicate S. aureus colonizing the nasal mucosa, the influence of mucin on the anti-staphylococcal activity was investigated. A disk agar-diffusion method was applied. Two reference strains of S. aureus (methicillin-sensitive S. aureus ATCC 29213 and methicillin-resistant S. aureus ATCC 33591) and 20 fresh clinical isolates were used. In the absence of mucin, the growth of all strains was inhibited by polihexanide concentrations of 0.1 mg/ml. In the presence of 0.25% mucin in the test medium, a concentration of 0.4 mg/ml was necessary to inhibit all strains. Mucin concentrations of 0.5% and 1%, that are even lower than the mucin concentrations in healthy nasal secretions, abolished the activity of the therapeutic concentrations of polihexanide. It is concluded that the inactivation of LS by mucin obstructs a reliable clearance of nasal S. aureus carriage.

  10. Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB.

    Directory of Open Access Journals (Sweden)

    Rebuma Firdessa

    Full Text Available Cutaneous leishmaniasis (CL is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed.Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide, a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN. PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB.Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.

  11. Encystation in Acanthamoeba castellanii: development of biocide resistance.

    Science.gov (United States)

    Lloyd, D; Turner, N A; Khunkitti, W; Hann, A C; Furr, J R; Russell, A D

    2001-01-01

    Since the early 1960s, axenic culture and the development of procedures for the induction of encystation have made Acanthamoeba spp. superb experimental systems for studies of cell biology and differentiation. More recently, since their roles as human pathogens causing keratitis and encephalitis have become widely recognized, it has become urgent to understand the parameters that determine differentiation, as cysts are much more resistant to biocides than are the trophozoites. Viability of trophozoites of the soil amoeba Acanthamoeba castellanii (Neff), is conveniently measured by its ability to form plaques on a lawn of Escherichia coli. Use of confocal laser scanning microscopy with Calcofluor white, Congo Red or the anionic oxonol dye, DiBAC4(3) or flow cytometry with propidium iodide diacetate and fluorescein or oxonol provides more rapid assessment. For cysts, the plaque method is still the best, because dye exclusion does not necessarily indicate viability and therefore the plate count method has been used to study the sequence of development of biocide resistance during the differentiation process. After two hours, resistance to HCl was apparent. Polyhexamethylene biguanide, benzalkonium chloride, propamidine isethionate, pentamidine isethionate, dibromopropamine isethionate, and H2O2 and moist heat, all lost effectiveness at between 14 and 24 h after trophozoites were inoculated into encystation media. Chlorhexidine diacetate resistance was observed at between 24 and 36 h. The molecular biology and biochemistry of the modifications that underlie these changes are now being investigated.

  12. [Treatment of Acanthamoeba keratitis: possibilities, problems, and new approaches].

    Science.gov (United States)

    Walochnik, Julia; Duchêne, Michael; Eibl, Hansjörg; Aspöck, Horst

    2003-01-01

    Acanthamoeba keratitis is a corneal disease associated predominantly with contact lens wear. The occurrence of Acanthamoeba keratitis has been rising since 1990 in correlation to the growing number of contact lens wearers. To date approximately 2000 cases have been published around the world. Due to the complicated diagnostics, the elaborate treatment and the usually bad compliance of the patients, Acanthamoeba keratitis unfortunately very often takes a serious progression, which may lead to serious visual loss and perforating keratoplasty. Today, local treatment with a combination of polyhexamethylene biguanide (PHMB) and propamidine isethionate (Brolene) is considered the first line therapy for Acanthamoeba keratitis. Alternatively also a combination of propamidine and chlorhexidine or neomycine achieves good therapeutic results. However, the complicated mode of application consistently remains a problem. The intensive local treatment, i.e. hourly application of therapeutics during the first three days day and night makes hospitalization inevitable. Moreover, sufficient efficacy can not always be achieved, and also resistance against propamidine has already been observed. Recently propamidine has sometimes been replaced by hexamidine, which seems to have a greater cysticidal activity. A new path might be struck by the application of alkylphosphocholines. These are phosphocholines esterified to aliphatic alcohols. They exhibit in vitro and in vivo antineoplastic activity and have been shown to be cytotoxic against Leishmania donovani, Trypanosoma cruzi, and Entamoeba histolytica. A recent study has demonstrated that particularly hexadecylphosphocholine is highly effective also against various strains of Acanthamoeba.

  13. Pharmacogenomics in type 2 diabetes: oral antidiabetic drugs.

    Science.gov (United States)

    Daniels, M A; Kan, C; Willmes, D M; Ismail, K; Pistrosch, F; Hopkins, D; Mingrone, G; Bornstein, S R; Birkenfeld, A L

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a fast progressing disease reaching pandemic proportions. T2DM is specifically harmful because of its severe secondary complications. In the course of the disease, most patients require treatment with oral antidiabetic drugs (OADs), for which a relatively large number of different options are available. The growing number of individuals affected by T2DM as well as marked interindividual differences in the response to treatment call for individualized therapeutic regimens that can maximize treatment efficacy and thus reduce side effects and costs. A large number of genetic polymorphisms have been described affecting the response to treatment with OADs; in this review, we summarize the most recent advances in this area of research. Extensive evidence exists for polymorphisms affecting pharmacokinetics and pharmacodynamics of biguanides and sulfonylureas. Data on incretin-based medications as well as the new class of sodium/glucose cotransporter 2 (SGLT2) inhibitors are just starting to emerge. With diabetes being a known comorbidity of several psychiatric disorders, we also review genetic polymorphisms possibly responsible for a common treatment response in both conditions. For all drug classes reviewed here, large prospective trials are necessary in order to consolidate the existing evidence and derive treatment schemes based on individual genetic traits.

  14. The role of Serratia marcescens in soft contact lens associated ocular infections. A review.

    Science.gov (United States)

    Parment, P A

    1997-02-01

    Serratia marcescens is a Gram negative rod which for a century and a half was considered a harmless saphrophyte. However, medical technology and the use of antibacterial agents have created ecological niches for this bacterium, which is now a medical problem. The bacterium is encountered in connection with contact lens keratitis, often associated with contaminated contact lens solutions. The concentrations of chlorhexidin and thiomersal required in contact lens solution to suppress the bacterium have been proved toxic to the eye. Modern contact lens solutions with biguanids have rapid killing kinetics, while in solutions with polyquaternium S. marcescens can survive in reduced numbers for up to 72 hours. The adherence of a specific isolate of Serratia to hydrogel lenses increased with decreased water content of the lenses. However, there has been no correlation between hydrophobicity markers or hemagglutinins and adherence to contact lenses or urinary tract epithelium. When handling medical plastic devices, such as contact lenses, strictly enforced hygiene remains the most important method to combat environmental bacteria such as Serratia marcescens.

  15. 我院2012~2014年抗糖尿病药物用药分析

    Institute of Scientific and Technical Information of China (English)

    董洪明

    2016-01-01

    目的:分析我院2012~2014年抗糖尿病药物的使用情况。方法:对我院2012~2014年抗糖尿病药物用药金额和用药频度(DDDs)等数据进行统计。结果:抗糖尿病药用药金额逐年增长。其中胰岛素类药物在所有抗糖尿病药物中的比重最大,口服降糖药以磺酰脲、双胍类为主。结论:我院连续3年抗糖尿病药应用基本稳定、合理。%Objective:To analyze the Utilization of antidiabetics in our hospital during the period 2012~2014. Methods:The consumption sum and DDDs of the antidiabetics in our hospital during the period 2012~2014 were investigated. Results: The consumption sum of antidiabetics increased year by year. Among them, the insulintype, drug sales in the largest proportion of sulfonylurea, biguanides took the lead among all the oral antidiabetics. Conclusion:The utilization of antidiabetics is our hospital during the period 2012~2014 is basically stable and reasonable.

  16. 我院门诊口服降糖药处方分析

    Institute of Scientific and Technical Information of China (English)

    张彩菊

    2013-01-01

    目的:调查门诊糖尿病患者口服降糖药物的应用情况。方法随机抽取含有口服降糖药的门诊处方,对口服降糖类药物的品种、数量及其合理性进行统计分析。结果用药频率居前三位的分别是双胍类、磺酰脲类及α-葡萄糖苷酶抑制剂类。结论依据各类口服降糖药物的作用机制和不同特点进行比较,我院口服降糖药物的应用是比较合理的。%objective: To evaluate the oral hypoglycemic agents used in our hospital. Method: The oral hypoglycemic agents are randomly selected and statistical analysed for type, quantity and the rationality in our hospital outpatient prescriptions.Results: The frequency of the top three are biguanides, sulfonylureas and α-glucosidase inhibitors.Conclusion: Based on the mechanism of action and the different characteristics of oral hypoglycemic drugs were compared, the application of oral hypoglycemic drugs in our hospital are reasonable.

  17. Effects of thiazolidinediones on the risk of bone fracture in patients with type 2 diabetes: a systematic review%噻唑烷二酮类药物对糖尿病患者骨折风险影响的系统评价

    Institute of Scientific and Technical Information of China (English)

    唐松涛; 周卫凤; 章秋; 孙业桓

    2012-01-01

    Objective To evaluate the effect of thiazolidinediones on the risk of bone fracture in patients with type 2 diabetes.Methods We searched for randomized controlled trials (RCTs) in the following electronic databases:MedLine,the Cochrane Library,Chinese BioMedical Literature Database (CBM),National Knowledge Infrastructure Database (CNKI),Chongqing VIP Information Database (VIP),Wanfang Data and collect all clinical controlled trials according to selection criteria.Quality assessment and data extraction were conducted by two reviewers independently.Disagreement were resolved through discussion.All data were analyzed by using Review Manager 5.0 software.Results Seven studies involving 16350 participants were selected in this analysis.The main results of meta-analysis showed that:thiazolidinediones significantly increased the risk of bone fractures among women (duration of treatment:three years) compared with that in placebo group(RR =1.99,95% CI:1.21-2.37,P <0.05);thiazolidinediones increased the risk of fractures among women (duration of treatment:one to three years)compared with biguanides or sulfonylureas (1.32 (0.29-5.87),P > 0.05) ; thiazolidinediones significantly increased the risk of fractures among women (duration of treatment:more than three years)compared with biguanides or sulfonylureas (1.94 (1.55-2.43),P < 0.05).No significant difference was found in the risk of bone fracture among men treated with thiazolidinediones and men treated with control drugs (P > 0.05).Thiazolidinediones significantly increased the risk of fractures of upper limb (1.85 (1.33-2.59),P < 0.05) and distal lower limb (2.74 (1.88-3.97),P < 0.05) among women (duration of treatment:more than three years) compared with biguanides or sulfonylureas; but there was no significant differences in the risk of fractures of spine among women treated with thiazolidinediones (duration of treatment:more than three years) compared with biguanides or sulfonylureas (1.72 (0.60-4.95),P

  18. 2型糖尿病患者红细胞胞浆钙调素活性变化的研究%A study of calmodulin activities of erythrocytes and its influencing factors in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    赵铁耘; 李秀钧; 吴兆锋; 张翔迅; 左凤琼

    2000-01-01

    ObjectiveTo evaluate the calmodulin (CaM) activities of erythrocytes and the possible causes toinfluence the changes of CaM levels in type 2 diabetic (DM2) patients.Methods 70 patients with DM2 were studied.Of the 70 patients, 46 were treated with only oral hypoglycemic agents (OHA) (32 treated with sulfonylureas, 20treated with biguanides, 4 treated with Acarbose).24 were on insulin or insulin+OHA for more than three weeks.Themeasurement of soluble CaM of erythrocytes was performed by the methods of Wallace RW.Results ①)The activities ofsoluble CaM of erythrocytes in DM2 were significantly lower than that in normal subjects ( P 0.05);而OHA组CaM活性较正常组显著降低(P<0.05)。③多因素分析显示2型糖尿病患者红细胞胞浆中CaM活性与年龄、体重指数(BMI)呈负相关,与空腹Ins水平呈正相关。结论2型糖尿病患者红细胞胞浆中可溶性CaM活性明显降低,而Ins治疗可使其红细胞胞浆中可溶性CaM活性有所恢复。

  19. Research Progress of 1-hour Hyperglycemia after Oral Glucose Tolerance Test%口服葡萄糖耐量试验后1h高血糖的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟志标

    2012-01-01

    1 -hour hyperglycemia during oral glucose tolerance test is a transitional state of abnormal glucose regulation from normal glucose tolerance to type 2 diabetes mellitus. It is an independent risk factor for both type 2 diabetes mellitus and cardiovascular disease. Compared with normal glucose tolerance persons,they have a decreased (3 cell function and higher probability of the conversion to impaired glucose regulation or type 2 diabetes mellitus. Weight control,reasonable exercise and drugs such as biguanides can improve insulin pcell function, thus decrease serum glucose level.%口服葡萄糖耐量试验后1h高血糖是正常糖耐量过渡到2型糖尿病的异常糖代谢状态,它是2型糖尿病和心血管疾病的独立危险因素,与正常血糖人群相比,其胰岛β细胞功能已经降低,更容易发展成为葡萄糖调节受损或2型糖尿病的状态.控制体质量,适当的运动,服用双胍类均可改善胰岛β细胞功能,从而降低血糖水平.

  20. 二甲双胍延长寿命的作用及其作用机制%Effects and mechanisms of metformin on lifespan extension

    Institute of Scientific and Technical Information of China (English)

    齐赫; 刘亭亭; 李国荣

    2012-01-01

    通过药理学方法来降低有机体的衰老率从而延长寿命已成为目前的研究热点之一.二甲双胍是一种用于治疗2型糖尿病的常用双胍类药物,研究显示二甲双胍可以延缓衰老并延长寿命,它可以通过激活腺苷酸活化蛋白激酶(AMPK)、抑制哺乳动物雷帕霉素靶蛋白(mTOR)及其下游相关分子发挥其抗衰老作用.本文对二甲双胍延长线虫、转基因小鼠和大鼠的寿命及其作用机制进行综述.%A research of pharmacological intervention that decreases the rate of organism aging to extend their life span is a perspective direction. Several studies have shown that metformin which is a biguanide class drug used in the treatment of type 2 diabetes mellitus can slow down aging and prolong life span. The possible mechanisms may be related to AMPK acti- vation, mTOR inhibition and its downstream molecules. This review describes the effects of metformin on lifespan extension in nematode, transgenic mice , rats and potential mechanisms.

  1. Retrospective Analysis of Application of Oral Hypoglycemic Agents in a Hospital of Chongqing in Recent 3 Years%重庆市某医院近3年口服降糖药应用分析

    Institute of Scientific and Technical Information of China (English)

    苏湲淇; 龙波

    2012-01-01

    Objective To analyze the application situation and the development trend of oral hypoglycemic agents in a grade A class 3 hospital of Chongqing. Methods The sale amount,DDDs and other indicators of the oral hypoglycemic agent application in the hospital during the year 2007-2009 were statistically analyzed. Results In the last three years,the hospital's total sales of oral hypoglycemic agents and the total amount of DDDs were increased year by year. Biguanide, a - glucosidase inhibitors, thiazolidinediones were mainly selected in clinical use. Conclusion The overall structure of hospital clinical use of oral hypoglycemic agents is reasonably stable.%目的 分析医院口服降糖药的应用情况与发展趋势.方法 对医院2007年至2009年口服降糖药的销售金额、用药频度等指标进行统计分析.结果 口服降糖药的总销售金额和总用药频度逐年增长,临床主要选用双胍类、α-葡萄糖苷酶抑制剂、噻唑烷二酮类药物.结论 口服降糖药临床用药整体结构合理稳定.

  2. 2008年至2010年我院口服降血糖药使用情况分析%Analysis on Use Status of Oral Hypoglycemic Agents in Our Hospital during 2008-2010

    Institute of Scientific and Technical Information of China (English)

    向光芳; 郑姣妮; 姜宁

    2012-01-01

    Objective To provide fundamental basis for rational use of medicines in clinic, we investigated the application of oral hypo-glycemic agents at our hospital. Methods The statistic analysis was carried out to study the use of oral hypoglycemic agents in our hospital during 2008 - 2010 using order of consumption sum and frequency degree analysis methods. Results Thiazolidinediones, a - glucosidase inhibitor and biguanides ranked the top three among all the oral hypoglycemic agents in consumption sum. The highest DDDs is rosiglita-zone, followed by glimepiride and acarbose. Conclusion The use of oral hypoglycemic agents in our hospital is basically reasonable.%目的 了解医院口服降血糖药的使用情况,为临床合理用药提供参考.方法 采用金额排序和频度分析法,对医院2008年至2010年口服降血糖药进行统计分析.结果 口服降糖药用药金额排前3位的分别是噻唑烷二酮类、a-糖苷酶抑制剂和双胍类;用药频度最高的是罗格列酮,其次是格列美脲和阿卡波糖.结论 医院口服降血糖药的使用基本合理.

  3. 精盐果蔬洗涤剂产品的研究与应用%Research and Application on the Salt Detergent Products for Fruit and Vegetable

    Institute of Scientific and Technical Information of China (English)

    杨丽梅; 刘烨; 吴融权

    2014-01-01

    Using the natural sterilization effect of salt, and choose "green" functional alkyl glycoside surfactants and fungicides polyhexamethylene biguanide hydrochloride as the raw material, we studied and developoed salt detergent products for fruit and vegetable. The test results proves that antimicrobial effect and pesticide residues removal of the salt detergent products for fruit and vegetable is quite good. And indicators in line with national standards.%利用盐的天然消毒杀菌作用,并选用“绿色”功能性表面活性剂烷基糖苷以及杀菌剂聚六亚甲基双胍盐酸盐为原料,研究开发精盐果蔬洗涤剂产品。通过测试结果证明,精盐果蔬洗涤剂产品的抑菌、农药残留去除效果良好,各项指标符合国家标准规定。

  4. Metformin displays in vitro and in vivo antitumor effect against osteosarcoma

    Science.gov (United States)

    Ko, Yunmi; Choi, Aery; Lee, Minyoung

    2016-01-01

    Purpose Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3–4 days for a period of 4 weeks. Results Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma. PMID:27721842

  5. Repurposing metformin: an old drug with new tricks in its binding pockets.

    Science.gov (United States)

    Pryor, Rosina; Cabreiro, Filipe

    2015-11-01

    Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world yet it also presents a grave challenge: as more people survive into later life, more also experience the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective novel treatments are still lacking. Alternative drug development strategies are now being explored, such as the repurposing of existing drugs used to treat other diseases. This can save a considerable amount of time and money since the pharmacokinetics, pharmacodynamics and safety profiles of these drugs are already established, effectively enabling preclinical studies to be bypassed. Metformin is one such drug currently being investigated for novel applications. The present review provides a thorough and detailed account of our current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide-protein interactions. It also focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function. Research in this area holds the key to solving many of the mysteries of our current understanding of drug action and concerted effects to provide sustained and long-life health.

  6. Antibacterial activity of THAM Trisphenylguanide against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Weaver, Alan J; Shepard, Joyce B; Wilkinson, Royce A; Watkins, Robert L; Walton, Sarah K; Radke, Amanda R; Wright, Thomas J; Awel, Milat B; Cooper, Catherine; Erikson, Elizabeth; Labib, Mohamed E; Voyich, Jovanka M; Teintze, Martin

    2014-01-01

    This study investigated the potential antibacterial activity of three series of compounds synthesized from 12 linear and branched polyamines with 2-8 amino groups, which were substituted to produce the corresponding guanides, biguanides, or phenylguanides, against Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Antibacterial activity was measured for each compound by determining the minimum inhibitory concentration against the bacteria, and the toxicity towards mammalian cells was determined. The most effective compound, THAM trisphenylguanide, was studied in time-to-kill and cytoplasmic leakage assays against methicillin-resistant Staphylococcus aureus (MRSA, USA300) in comparison to chlorhexidine. Preliminary toxicity and MRSA challenge studies in mice were also conducted on this compound. THAM trisphenylguanide showed significant antibacterial activity (MIC ∼1 mg/L) and selectivity against MRSA relative to all the other bacteria examined. In time-to-kill assays it showed increased antimicrobial activity against MRSA versus chlorhexidine. It induced leakage of cytoplasmic content at concentrations that did not reduce cell viability, suggesting the mechanism of action may involve membrane disruption. Using an intraperitoneal mouse model of invasive MRSA disease, THAM trisphenylguanide reduced bacterial burden locally and in deeper tissues. This study has identified a novel guanide compound with selective microbicidal activity against Staphylococcus aureus, including a methicillin-resistant (MRSA) strain.

  7. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

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    Pragya Tiwari

    2015-01-01

    Full Text Available Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

  8. Drug Use Evaluation In Diabetic Patients at Out Patient Department Gorakhpur

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    Tripathi Poonam, Pandey Awanish, Pandey Rishabh, Goswamy Shambaditya & Srivatava Rashmi

    2010-12-01

    Full Text Available Objectives: The aim of the present study was to assess drug utilization in diabetes patients as a quantitative type of prescription auditing to generate data with respect to their extent variability of drug usage in a heath care system of the area of Gorakhpur.Material and Methods: The data for the study was collected from the survey conducted in February 2009-April 2009 at various hospitals of Gorakhpur. Two hundred diabetic patients were interviewed as a pre designed questionnaire based on clinical details. All the diabetic patients who visited the OPD during the study period enrolled in the study.Results: The pattern of drug prescription in diabetes showed that sulfonylurea (65% and biguanides (65% were most frequently prescribed followed by thiazolidinediones (23%and alpha glucosidase inhibitors (3%. Insulin was prescribed in 31 (15.5% patients. Among Most common co-existing illness was found hypertension (31.97 %. Majority of drugs were prescribed in oral dosage form (84.5 % followed by Parenteral (15.5 %.Conclusion: It is concluded that the present prescribing pattern of antidiabetic drugs Gorakhpur does not completely meet standard guidelines of diabetic treatment. Hence there is a need to encourage physicians of Gorakhpur to follow the guidelines while treating diabetes.

  9. Secular Trends in the Clinical Characteristics of Type 2 Diabetic Patients With Severe Hypoglycemia Between 2008 and 2013

    Science.gov (United States)

    Ito, Hiroyuki; Tsugami, Emiko; Ando, Shigenori; Imai, Ayano; Matsumoto, Suzuko; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Abe, Mariko; Antoku, Shinichi; Mifune, Mizuo; Togane, Michiko

    2016-01-01

    Background We investigated the trends in the clinical characteristics and prescriptions of type 2 diabetic patients with severe hypoglycemia because the prescription rate of antidiabetic agents has significantly changed recently. Methods A total of 193 patients with type 2 diabetes with severe hypoglycemia induced by antidiabetic agents between 2008 and 2013 were divided into three groups based on the period of visit: 2008 - 2009, 2010 - 2011 and 2012 - 2013. Results While the proportion of patients with severe hypoglycemia using insulin (from 55% to 74%), biguanides (from 6% to 20%), glinides, and dipeptidyl peptidase-4 inhibitors significantly increased, those using sulfonylureas (from 45% to 20%) significantly decreased. Errors of drug use significantly increased as a trigger of hypoglycemia in recent years. The number of antidiabetic agents (from 1.9 ± 0.6 to 2.3 ± 0.7), non-diabetic agents (from 2.3 ± 2.4 to 4.3 ± 3.3), and total drugs prescribed were significantly higher in recent years among patients receiving insulin therapy. Conclusions Polypharmacy especially in patients receiving insulin therapy and errors of drug use have increased in type 2 diabetic patients with severe hypoglycemia in recent years. Intensive education in the usage rule of drugs is considered to be important in order to prevent severe hypoglycemia. PMID:27635175

  10. Pharmacogenetic studies update in type 2 diabetes mellitus

    Science.gov (United States)

    Singh, Shalini; Usman, Kauser; Banerjee, Monisha

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment. PMID:27555891

  11. Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Zhao Liu

    Full Text Available Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error. Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

  12. Analysis of the use of drugs in cardiovascular and antidiabetic primary health care according to age - doi: 10.4025/actascihealthsci.v35i1.10694

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    Marcos Aparecido Sarria Cabrera

    2013-03-01

    Full Text Available The population of elderly and non-elderly users of a Basic Health Unit (UBS was interviewed regarding the use of cardiovascular and anti-diabetic medications, as well as the adverse effects that were noted. Hypertension and diabetes mellitus are conditions involving complications and compromise the quality of life of patients. The objective was to build a profile of these users. The cross-sectional study was carried out on patients older than 18 years of age and users of cardiovascular or anti-diabetic drugs in Centro Social Urbano UBS, located in Londrina – PR, Brazil. The result revealed the following statistically significant variables: lower use of beta blockers (p = 0.012 and metformin (p = 0.05 among the elderly compared to the overall average, and higher acetylsalicylic acid (ASA (p = 0.006 use in people over 64 years of age. Reported adverse symptoms were lower among those over 64 years old (p = 0.03. Angiotensin-converting enzyme (ACE inhibitors are the most used (63.5%, followed by diuretics (54.9% and beta-blockers (27.7%. Among diabetic patients, 23.2% were using biguanides and 15.9% sulfonylureas; only 6.6% were insulin-dependent. The conclusion is that drug therapies within the sample were mostly in accordance with current guidelines.  

  13. Noninsulin pharmacological management of type 1 diabetes mellitus

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    Vishvas Garg

    2011-01-01

    Full Text Available The injectable nature and other shortcomings of insulin have stimulated interest in studying the noninsulin pharmacological therapies to manage type 1 diabetes mellitus (T1DM. The purpose of this study is to conduct a systematic literature review of noninsulin pharmacological therapies for the management of T1DM. For this, the following PubMed search was conducted: Diabetes Mellitus, Type 1/therapy"[Mesh] Limits: Review Sort by: Publication Date. After applying various inclusion and exclusion criteria, a total of 63 studies were reviewed. Based on this review, noninsulin pharmacological therapies can be divided into following classes: (1 Insulin-sensitizing agents (biguanides and thiazolidinediones, (2 gastrointestinal nutrient absorption modulators (α-Glucosidase inhibitors and amylin, (3 immunotherapeutic agents, (4 incretin-based therapies, (5 recombinant human insulin-like growth factors, and (6 other promising therapeutics. Some of these are already used either as monotherapy or adjuvant to insulin, whereas, to manage T1DM, the benefits and risks of the others are still under evaluation. Nonetheless, insulin still remains the cornerstone to manage the T1DM.

  14. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling.

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    Sakae Saito

    Full Text Available Inhibiting the unfolded protein response (UPR can be a therapeutic approach, especially for targeting the tumor microenvironment. Here, we show that compound C (also known as dorsomorphin, a small-molecule inhibitor of AMP-activated protein kinase (AMPK and bone morphogenetic protein (BMP signaling, inhibit the UPR-induced transcription program depending on the glucose deprivation conditions. We found that compound C prevented UPR marker glucose-regulated protein 78 (GRP78 accumulation and exerted enhanced cytotoxicity during glucose deprivation. Gene expression profiling, together with biochemical analysis, revealed that compound C had a unique mode of action to suppress the transcriptional activation of UPR-targeted genes, as compared with the classic UPR inhibitors versipelostatin and biguanides. Surprisingly, the UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition. We further found that combination treatments of compound C and the classic UPR inhibitors resulted in synergistic cell death with UPR suppression during glucose deprivation. Our findings demonstrate that compound C could be a unique tool for developing a UPR-targeted antitumor therapy.

  15. Novel guanide-substituted compounds bind to CXCR4 and inhibit breast cancer metastasis.

    Science.gov (United States)

    Shepard, Joyce B; Wilkinson, Royce A; Starkey, Jean R; Teintze, Martin

    2014-01-01

    CXCR4 has been shown to be overexpressed on breast cancer cells including the human MDA-MB-231 cell line. Cancer cells overexpressing the CXCR4 receptor are capable of undergoing metastasis to organs expressing high levels of CXCL12. We have synthesized numerous guanide, biguanide, phenylguanide, and naphthylguanide compounds that bind to CXCR4 at the CXCL12-binding site and thus should prevent CXCR4-facilitated cancer metastasis. The novel compounds presented here were tested for CXCR4 affinity, toxicity, receptor activation, and for their ability to prevent breast cancer metastases. Three of the compounds bound to CXCR4 at IC50 values of 0.06-0.2 μmol/l, with no associated cell toxicity or receptor activation at these concentrations. These high CXCR4 affinity compounds also showed inhibition of in-vitro wound migration. They were then tested in an in-vivo mouse breast cancer lung colony model. All of these compounds showed reductions in the number of MDA-MB-231 lung metastases compared with mock-treated control mice without evidence of cardiac, liver, or kidney toxicity in treated mice.

  16. Modes of Inhibition of α-Amylase and α-Glucosidase by Aqueous Extract of Morinda lucida Benth Leaf

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    M. I. Kazeem

    2013-01-01

    Full Text Available Diabetes mellitus is a metabolic disorder of glucose metabolism. The management of blood glucose level is the hallmark in the treatment of this disease. This may be achieved through the use of oral hypoglycemic drugs such as biguanides, insulin secretagogues, and α-glucosidase inhibitors. The purpose of the present study was to investigate the inhibitory effect of Morinda lucida leaf extracts on the activities of α-amylase and α-glucosidase. This was performed using α-amylase from Aspergillus oryzae and α-glucosidase from Saccharomyces cerevisiae. Aqueous extract of Morinda lucida gave the highest percentage yield (9.99% of the plant out of the three extracts (compared to acetone and ethanolic extracts and possesses the highest inhibitory activity against α-amylase (IC50 value of 2.30 mg/mL and α-glucosidase (IC50 value of 2.00 mg/mL. Kinetic analysis revealed that the aqueous extract of this plant leaf inhibited the α-amylase competitively but displayed mixed noncompetitive mode of inhibition towards α-glucosidase. It can be concluded that aqueous extract of Morinda lucida exhibited the best inhibitory activity on the two enzymes studied and the presence of phytochemicals like flavonoids, saponins, and tannins may have contributed greatly to the inhibitory activity of the plant extract.

  17. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes.

    Science.gov (United States)

    Chindera, Kantaraja; Mahato, Manohar; Sharma, Ashwani Kumar; Horsley, Harry; Kloc-Muniak, Klaudia; Kamaruzzaman, Nor Fadhilah; Kumar, Satish; McFarlane, Alexander; Stach, Jem; Bentin, Thomas; Good, Liam

    2016-03-21

    To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.

  18. Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus

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    B. Siddhartha Kumar

    2012-04-01

    Full Text Available Diabetes mellitus (DM and osteoporosis are the two important public health problems in India. The burden of both these conditions is expected to increase in the near future in view of changing lifestyle habits and ageing population. Indians are at risk of osteoporosis due to their low body mass index (BMI, genetic predisposition and nutritional factors. The diseases type 1 DM and type 2 DM (T2DM are associated with increased fracture risk in the disease population, in spite of difference in the bone mineral density (BMD. An increase in fracture risk is also reported among older patients with T2DM despite frequently reported normal or increased BMD. Administration of insulin stimulates osteoblast activity and bone mineral apposition rates. The impact of endogenous insulin production, insulin sensitivity, and exogenous insulin administration as an anabolic agent for bone in T2DM has not been clarified. Biguanides and sulphonylureas do not appear to have adverse effects on BMD. Preclinical evidence suggests that incretin-based drugs may be beneficial for bone, but clinical evidence to support this hypothesis is not yet available. Thiazolidinedione (TZD group of agents have been implicated in causing osteoporosis in various animal studies and some human studies available till date. The debate regarding this is issue is still ongoing. Randomized controlled studies with larger sample size preferably involving multiple centres, multiple ethnicities are required to answer these queries.

  19. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

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    Mozhgan Dorkhan

    2007-11-01

    Full Text Available Mozhgan Dorkhan, Anders FridDepartment of Clinical Sciences, Division of Diabetes and Endocrinology, Lund University, Malmö University Hospital, SwedenAbstract: Type 2 diabetes (T2D is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/glinides or insulin, biguanides, and thiazolidinediones (TZDs respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.Keywords: pioglitazone, glimepiride, type 2 diabetes, thiazolidinediones, sulfonylureas

  20. Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants.

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    Lisa F Dawson

    Full Text Available The increased prevalence of Clostridium difficile infection (CDI has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs, peroxygens, quaternary ammonium compounds (QAC and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon®, Newgenn®, Proceine 40® and Hibiscrub®. Whereas, for Steri7® and Biocleanse® the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe® was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR-ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings.

  1. Allosteric activation of the 5-HT3AB receptor by mCPBG.

    Science.gov (United States)

    Miles, Timothy F; Lester, Henry A; Dougherty, Dennis A

    2015-04-01

    The 5-HT3AB receptor contains three A and two B subunits in an A-A-B-A-B order. However, serotonin function at the 5-HT3AB receptor has been shown to depend solely on the A-A interface present in the homomeric receptor. Using mutations at sites on both the primary (E122) and complementary (Y146) faces of the B subunit, we demonstrate that meta-chlorophenyl biguanide (mCPBG), a 5-HT3 selective agonist, is capable of binding to and activating the 5-HT3AB receptor at all five subunit interfaces of the heteromer. Further, mCPBG is capable of allosterically modulating the activity of serotonin from these sites. While these five binding sites are similar enough that they conform to a monophasic dose - response relationship, we uncover subtle differences in the heteromeric binding sites. We also find that the A-A interface appears to contribute disproportionately to the efficacy of 5-HT3AB receptor activation.

  2. Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

    Science.gov (United States)

    Liu, Zhao; Ren, Lidong; Liu, Chenghao; Xia, Tiansong; Zha, Xiaoming; Wang, Shui

    2015-01-01

    Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error). Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition) and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

  3. Interaction and effectiveness of antimicrobials along with healing-promoting agents in a novel biocellulose wound dressing.

    Science.gov (United States)

    Napavichayanun, Supamas; Amornsudthiwat, Phakdee; Pienpinijtham, Prompong; Aramwit, Pornanong

    2015-10-01

    An ideal wound dressing should keep the wound moist, allow oxygen permeation, adsorb wound exudate, accelerate re-epithelialization for wound closure, reduce pain and healing time, and prevent infection. Our novel biocellulose-based wound dressing was composed of three components: 1) biocellulose (BC), intended to create a moist and oxygen-permeated environment with exudate adsorption; 2) silk sericin (SS) known for its enhancement of collagen type I production, which is critical for re-epithelialization; and 3) the antiseptic polyhexamethylene biguanide (PHMB). To deliver an effective BC wound dressing, the interactions between the components (PHMB vs. SS) needed to be thoroughly analyzed. In this study, we investigated important parameters such as the loading sequence, loading concentration, and loading amount of the active compounds to ensure that the BC wound dressing could provide both antimicrobial activity and promote collagen production during healing. The loading sequence of SS and PHMB into BC was critical to maintain PHMB antimicrobial activity; silk sericin needed to be loaded before PHMB to avoid any negative impacts. The minimum PHMB concentration was 0.3% w/v for effective elimination of all tested bacteria (Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa). The amounts of SS and PHMB in BC were optimized to ensure that the dressings released the optimal amounts of both SS to enhance fibroblast collagen production and PHMB for effective antimicrobial activity.

  4. Pharmacologically-induced metabolic acidosis: a review.

    Science.gov (United States)

    Liamis, George; Milionis, Haralampos J; Elisaf, Moses

    2010-05-01

    Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised.

  5. Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy.

    Science.gov (United States)

    Andrès, Emmanuel; Vidal-Alaball, Josep; Federici, Laure; Loukili, Noureddine Henoun; Zimmer, Jacques; Kaltenbach, Georges

    2007-10-01

    The aim of this work was to review the literature concerning cobalamin deficiency in elderly patients. Articles were identified through searches of PubMed-MEDLINE (January 1990 to June 2006), restricted to: English and French language, human subjects, elderly patients (>65 years), clinical trial, review and guidelines. Additional unpublished data from our cohort with cobalamin deficiency at the University Hospital of Strasbourg, France, were also considered. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. The recently identified food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or from its binding proteins. This syndrome is usually the consequence of atrophic gastritis, related or not to Helicobacter pylori infection, and of the long-term ingestion of antacids and biguanides (in around 60% of the patients). Management of cobalamin deficiency has been well established with the use of cobalamin injections. However, new routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption.

  6. Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders

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    Birgit Waltenberger

    2016-06-01

    Full Text Available Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives in the fight against metabolic disease, is also included. The present review aims to serve as an “opening” of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease.

  7. Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders.

    Science.gov (United States)

    Waltenberger, Birgit; Mocan, Andrei; Šmejkal, Karel; Heiss, Elke H; Atanasov, Atanas G

    2016-06-22

    Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an "opening" of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease.

  8. Effects of insulin and other antihyperglycaemic agents on lipid profiles of patients with diabetes.

    Science.gov (United States)

    Chaudhuri, A; Dandona, P

    2011-10-01

    Increased morbidity and mortality risk due to diabetes-associated cardiovascular diseases is partly associated with hyperglycaemia as well as dyslipidaemia. Pharmacological treatment of diabetic hyperglycaemia involves the use of the older oral antidiabetic drugs [OADs: biguanides, sulphonylureas (SUs), α-glucosidase inhibitors and thiazolidinediones], insulin (human and analogues) and/or incretin-based therapies (glucagon-like peptide-1 analogues and dipeptidyl peptidase 4 inhibitors). Many of these agents have also been suggested to improve lipid profiles in patients with diabetes. These effects may have benefits on cardiovascular risk beyond glucose-lowering actions. This review discusses the effects of OADs, insulins and incretin-based therapies on lipid variables along with the possible mechanisms and clinical implications of these findings. The effects of intensive versus conventional antihyperglycaemic therapy on cardiovascular outcomes and lipid profiles are also discussed. A major conclusion of this review is that agents within the same class of OADs can have different effects on lipid variables and that contrary to the findings in experimental models, insulin has been shown to have beneficial effects on lipid variables in clinical trials. Further studies are needed to understand the precise effect and the mechanisms of these effects of insulin on lipids.

  9. Versatile synthesis of PHMB-stabilized silver nanoparticles and their significant stimulating effect on fodder beet (Beta vulgaris L.).

    Science.gov (United States)

    Gusev, Alexander А; Kudrinsky, Alexey A; Zakharova, Olga V; Klimov, Alexey I; Zherebin, Pavel M; Lisichkin, George V; Vasyukova, Inna A; Denisov, Albert N; Krutyakov, Yurii A

    2016-05-01

    Silver nanoparticles (AgNPs) are well-known bactericidal agents. However, information about the influence of AgNPs on the morphometric parameters and biochemical status of most important agricultural crops is limited. The present study reports the influence of AgNPs stabilized with cationic polymer polyhexamethylene biguanide hydrochloride (PHMB) on growth, development, and biochemical status of fodder beet Beta vulgaris L. under laboratory and greenhouse conditions. PHMB-stabilized AgNPs were obtained via sodium borohydride reduction of silver nitrate in an aqueous solution. The average diameter of thus prepared AgNPs was 10 nm. It appears that the results of experiments with laboratory-grown beets in the nanosilver-containing medium, where germination of seeds and growth of roots were suppressed, do not correlate with the results of greenhouse experiments. The observed growth-stimulating action of PHMB-stabilized AgNPs can be explained by the change of activity of oxidases and, consequently, by the change of auxins amount in plant tissues. In beets grown in the presence of PHMB-stabilized AgNPs no negative deviations of biological parameters from normal values were registered. Furthermore, the SEM/EDS examination revealed no presence of silver in the tissues of the studied plants.

  10. Importance of porins for biocide efficacy against Mycobacterium smegmatis.

    Science.gov (United States)

    Frenzel, Elrike; Schmidt, Stefan; Niederweis, Michael; Steinhauer, Katrin

    2011-05-01

    Mycobacteria are among the microorganisms least susceptible to biocides but cause devastating diseases, such as tuberculosis, and increasingly opportunistic infections. The exceptional resistance of mycobacteria to toxic solutes is due to an unusual outer membrane, which acts as an efficient permeability barrier, in synergy with other resistance mechanisms. Porins are channel-forming proteins in the outer membrane of mycobacteria. In this study we used the alamarBlue assay to show that the deletion of Msp porins in isogenic mutants increased the resistance of Mycobacterium smegmatis to isothiazolinones (methylchloroisothiazolinone [MCI]/methylisothiazolinone [MI] and octylisothiazolinone [2-n-octyl-4-isothiazolin-3-one; OIT]), formaldehyde-releasing biocides {hexahydrotriazine [1,3,5-tris (2-hydroxyethyl)-hexahydrotriazine; HHT] and methylenbisoxazolidine [N,N'-methylene-bis-5-(methyloxazolidine); MBO]}, and the lipophilic biocides polyhexamethylene biguanide and octenidine dihydrochloride 2- to 16-fold. Furthermore, the susceptibility of the porin triple mutant against a complex disinfectant was decreased 8-fold compared to wild-type (wt) M. smegmatis. Efficacy testing in the quantitative suspension test EN 14348 revealed 100-fold improved survival of the porin mutant in the presence of this biocide. These findings underline the importance of porins for the susceptibility of M. smegmatis to biocides.

  11. The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II.

    Science.gov (United States)

    Kravchuk, Ekaterina; Grineva, Elena; Bairamov, Alekber; Galagudza, Michael; Vlasov, Timur

    2011-01-01

    In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P < .01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

  12. The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

    Directory of Open Access Journals (Sweden)

    Ekaterina Kravchuk

    2011-01-01

    Full Text Available In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM. Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P<.01, indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

  13. Effects of sulfonylureas on tumor growth: a review of the literature.

    Science.gov (United States)

    Pasello, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

    2013-01-01

    Type 2 diabetes mellitus patients are at higher cancer risk, probably because of hyperinsulinemia and insulin growth factor 1 pathway activation. The effects of antidiabetic drugs on cancer risk have been described and discussed in several studies suggesting opposite effects of the biguanide metformin and sulfonylureas on cancer incidence and mortality. The anticancer mechanisms of metformin have been clarified, and some clinical studies, particularly in breast cancer patients, have been published or are currently ongoing; however, data about the effects of sulfonylureas on cancer growth are less consistent. The aims of this work are to review preclinical evidence of second-generation sulfonylureas effects on tumor growth, to clarify the potential mechanisms of action, and to identify possible metabolic targets for patient selection. Most evidence is on the adenosine triphosphate-sensitive potassium channels inhibitor glibenclamide, which interacts with reactive oxygen species production thus inducing cancer cell death. Among diarylsulfonylureas, next-generation DW2282 derivatives are particularly promising because of the proapoptotic activity in multidrug-resistant cells.

  14. 二甲双胍的心血管保护作用%Cardiovascular protective effects of metformin

    Institute of Scientific and Technical Information of China (English)

    方丽娟; 刘乃丰

    2011-01-01

    二甲双胍(Metformin)属双胍类药物,作为口服降糖药应用于2型糖尿病(T2DM)已有50年的历程,其降糖作用已得到公认.近年越来越多的研究发现,二甲双胍具有降糖以外的心血管保护作用,能抑制动脉粥样硬化(Atherosclerosis,AS)、心衰、心肌梗死等心血管病的发生和发展.但二甲双胍确切的心血管保护机制仍不明确,本文综述了二甲双胍对心血管疾病的作用,并探讨其可能的作用机制.%Metformin belongs to biguanide drugs, used as oral hypoglycemic agents in type 2 diabetes (T2DM) for 50 years, and its anti-hyperglycemic effect has been recognized.Furthermore, in recent years more and more studies found that metformin has additional cardiovascular protective effects, including the inhibition of atherosclerosis (AS), heart failure and myocardial infarction.However, the specific effect of metformin on cardiovascular protection is still unclear.This article reviews the effect of metformin in cardiovascular disease and discusses its possible mechanisms.

  15. Antibacterial activity of THAM Trisphenylguanide against methicillin-resistant Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Alan J Weaver

    Full Text Available This study investigated the potential antibacterial activity of three series of compounds synthesized from 12 linear and branched polyamines with 2-8 amino groups, which were substituted to produce the corresponding guanides, biguanides, or phenylguanides, against Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Antibacterial activity was measured for each compound by determining the minimum inhibitory concentration against the bacteria, and the toxicity towards mammalian cells was determined. The most effective compound, THAM trisphenylguanide, was studied in time-to-kill and cytoplasmic leakage assays against methicillin-resistant Staphylococcus aureus (MRSA, USA300 in comparison to chlorhexidine. Preliminary toxicity and MRSA challenge studies in mice were also conducted on this compound. THAM trisphenylguanide showed significant antibacterial activity (MIC ∼1 mg/L and selectivity against MRSA relative to all the other bacteria examined. In time-to-kill assays it showed increased antimicrobial activity against MRSA versus chlorhexidine. It induced leakage of cytoplasmic content at concentrations that did not reduce cell viability, suggesting the mechanism of action may involve membrane disruption. Using an intraperitoneal mouse model of invasive MRSA disease, THAM trisphenylguanide reduced bacterial burden locally and in deeper tissues. This study has identified a novel guanide compound with selective microbicidal activity against Staphylococcus aureus, including a methicillin-resistant (MRSA strain.

  16. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus.

    Science.gov (United States)

    Tahrani, Abd A; Barnett, Anthony H; Bailey, Clifford J

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

  17. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice

    Science.gov (United States)

    Anisimov, Vladimir N.; Berstein, Lev M.; Popovich, Irina G.; Zabezhinski, Mark A.; Egormin, Peter A.; Piskunova, Tatiana S.; Semenchenko, Anna V.; Tyndyk, Margarita L.; Yurova, Maria N.; Kovalenko, Irina G.; Poroshina, Tatiana E.

    2011-01-01

    Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer in mice, although its effects vary, depending on mice strain and gender. Here we showed that chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreased body temperature and postponed age-related switch-off of estrous function. Surprisingly, metformin did not affect levels of serum cholesterol, triglycerides, glucose and insulin. Treatment with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. The treatment started at the age of 9 months insignificantly increased mean life span by only 6%, whereas the treatment started at the age of 15 months failed to increase life span. The mean life span of tumor-free mice was increased by 21% in ‘the youngest group’, by 7% in ‘middle-aged group’ and in contrast was reduced by 13% in ‘the oldest group’. When started at the age of 3 and 9 months, metformin delayed the first tumor detection by 22% and 25%, correspondingly. Thus, in female SHR mice, metformin increased life span and postponed tumors when started at the young and middle but not at the old age. In contrast, metformin improves reproductive function when started at any age. PMID:21386129

  18. Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice

    Science.gov (United States)

    Anisimov, Vladimir N.; Piskunova, Tatiana S.; Popovich, Irina G.; Zabezhinski, Mark A.; Tyndyk, Margarita L.; Egormin, Peter A.; Yurova, Maria N.; Rosenfeld, Svetlana V.; Semenchenko, Anna V.; Kovalenko, Irina G.; Poroshina, Tatiana E.; Berstein, Lev M.

    2010-01-01

    Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. It is possible that the life-prolonging effects of calorie restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway (which mimetic effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. Antidiabetic biguanides are most promising among them. The chronic treatment of inbred 129/Sv mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but failed to influence the dynamics of body weight, decreased by 13.4% the mean life span of male mice and slightly increased the mean life span of female mice (by 4.4%). The treatment with metformin failed influence spontaneous tumor incidence in male 129/Sv mice, decreased by 3.5 times the incidence of malignant neoplasms in female mice while somewhat stimulated formation of benign vascular tumors in the latter. PMID:21164223

  19. 1,1-Dimethylbiguanidium(2+ dinitrate

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    Michaela Fridrichová

    2012-01-01

    Full Text Available In the crystal structure of the title compound, C4H13N52+·2NO3−, the main intermolecular interactions are the N—H...O hydrogen bonds between the cationic amino groups and the O atoms of the nitrate ions. All amino H atoms and nitrate O atoms are involved in the three-dimensional hydrogen-bond network. There are two graph-set motifs R22(8, which include the amino groups connected to the N atoms in the biguanide 3-, 4- and 5-positions, and the O atoms of a nitrate ion. They are extended along the a axis. An O atom of the second nitrate ion is involved in a graph-set motif C(4 that is a part of a helix-like N—H...O...H—N—H...O... chain oriented along the b axis. There are also two weak C—H...O interactions in the crystal structure.

  20. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

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    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  1. Acidosis láctica grave asociada a intoxicación por metformina Severe lactic acidosis associated to metformin intoxication

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    M. S. Holanda Peña

    2007-02-01

    Full Text Available La metformina es una biguanida ampliamente utilizada en el tratamiento de la diabetes mellitus tipo II. Entre los efectos secundarios derivados de su empleo destaca por su baja frecuencia de presentación pero potencial gravedad la acidosis láctica. El diagnóstico de la misma se basa generalmente en la coexistencia de la acidosis láctica en un paciente en tratamiento con metformina con uno o mas factores de riesgo para la presentación de la misma. El desarrollo de acidosis láctica en relación con el tratamiento con metformina conlleva una mortalidad que oscila entre 50-80%.Metformin is a biguanide extensively used in the treatment of type II diabetes mellitus. Between the nocive effects of the metformin emphasizes tha lactic acidosis because of its low frecuency but potential severity. The diagnosis of the poisoning due to metformin is based on the coexistence of lactic acidosis and one or more of the risk factors. The development of lactic acidosis in metformin poisoning is associated to a range of 50-80% of mortality.

  2. A study on concept of P- drug selection among rural general practitioners

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    Priyadarshini Bai G.

    2016-12-01

    Full Text Available Background: The objective of the study was to assess the awareness of P- drug selection among rural general practitioners’s (GP for common medical conditions. Methods: Fifty general practitioners in Tumakuru district were provided with proformas for selection of P- drugs for mild to moderate hypertension, diabetes, upper respiratory tract infections and acid peptic disease based on safety, affordability, need, and efficacy (SANE criteria. Results: Forty one GP’s responded by completing the proformas. Seventeen of them were aware of the concept of P- drug selection. In hypertension, beta blockers followed by Angiotensin Converting Enzyme (ACE inhibitors were most commonly preferred. In diabetes, biguanides followed by sulfonylureas were preferred as oral hypoglycemic agents. Ampicillin, Ciprofloxacin and Cotrimoxazole were the commonly used antibiotics for upper respiratory tract infections. Ranitidine and antacids were preferred for acid peptic disease. Affordability followed by efficacy was the deciding criteria for P- drug selection. Conclusions: There is lack of awareness of P- drug selection among many rural GP’s. Therefore, there is necessity to create awareness about P- drug selection through continued medical education for rational use of drugs.

  3. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  4. 二甲双胍联合综合促排卵治疗多囊卵巢综合征的临床研究%Clinical research of metformin combined ovulation therapy in women with polycystic ovsry syndrome

    Institute of Scientific and Technical Information of China (English)

    全启花; 余琳; 陈敦金; 杨洁

    2009-01-01

    Objective To investigate the clinical effects of metformin combined ovulation therapy on women with polycystie ovary syndrome(PCOS).Methods sixty-patients with PCOS were classified into 2 groups, the test group were treat by dimethyl biguanide and clomiphene and CC-hMG/hCG, the control group only used CC-hMG/hCG, all of them were be treated one cycle.Results there were 2 case had pregnancy during taking dimethyl biguanide orally. Effective case were 27, that is 27/28, and the time and the dose of use the CC-hMG/ hCG were (3.84±0.6)days and(7.84±1.8) rami individually, only one case were inefficacious.the control group had 25 effective case, and the time and the dose of use the CC-hMG/hCG were (4.84±1.6) days and (9.34±2.7) rami individually, there were significant difference between the two groups(P<0.05).Conclusion Metformin may effectively improve insulin resistance, reduce serum androgen level, and recover ovulation function in women with PCOS.%目的 探讨二甲双胍联合氯米芬-促性腺激素在多囊卵巢综合征(PCOS)患者治疗中的临床疗效观察.方法 60例PCOS患者,试验组应用二甲双胍联合氯米芬-促性腺激素,对照组只应用CC-hMG/hCG促排卵,具体使用方法同观察组.两组各治疗一个周期.结果 两组治疗情况比较,观察组30例中,2例口服二甲双胍期间妊娠,28例促排卵治疗,有效27例,且均使用hCG诱发排卵,无反应1例;对照组促排卵治疗有效25例,1例因卵巢轻度刺激放弃hCG诱发排卵,无反应5例.有效病例中使用HMG治疗天数及用药剂量观察组分别(3.84±0.6)天和(7.84±1.8)支,对照组分别为(4.84±1.6)天和(9.34±2.7)支.两组比较差异有显著性(P<0.01).结论 二甲双胍联合氯米芬可有效地改善PCOS患者的胰岛素抵抗,降低血雄激素水平,诱导排卵,并恢复生育功能.

  5. Características do tratamento medicamentoso de pacientes diabéticos de uma Unidade Básica de Saúde Diabetic patient’s drug treatment characteristics in a Basic Health Unit

    Directory of Open Access Journals (Sweden)

    Liudmila Otero Miyar

    2010-07-01

    multidisciplinary team in the Basic Health Unit, Federal University of Amapá (UBS/UNIFAP. Materials and Methods: The study design was descriptive, cross-sectional. Its population was composed of 40 type 2 diabetic patients who met the inclusion criteria. The study period was from May 2007 to April 2008. The variables investigated were the treatment characteristics (prescribed medication and medication mentioned by the patient and the treatment complexity (association of medication, the amount of pills the patient takes a day, the number of times these pills are used by day and the time of medication. The SPSS program was used for data analysis. Results: The results showed that 85.0% of patients reported to do the drug treatment, 82.5% to follow a diet plan and 42.5% to perform a physical activity plan. About the treatment characteristics, in relation to the drugs, we have shown that the most prevalent are those who make use of Sulfonylureas 67.7%, Biguanides 41.2% and insulin 20.6%. Conclusion: The treatment characteristics investigated showed differences between the prescribed drugs and the ones reported by the patients. In the complexity, it was found that 54.5% use combined medications. Some patients using Biguanide and Sulfonylurea reported incorrect number of tablets taken by day, as well as erroneous values in relation to the number of times per day they should take the medication.

  6. Polyamine analogues targeting epigenetic gene regulation.

    Science.gov (United States)

    Huang, Yi; Marton, Laurence J; Woster, Patrick M; Casero, Robert A

    2009-11-04

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of

  7. Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defence network

    Directory of Open Access Journals (Sweden)

    Orla eCondell

    2014-08-01

    Full Text Available Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents.We generated a Salmonella enterica serovar Typhimurium isolate (ST24CHX that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defence network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defence network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism towards anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defence response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism.These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent.

  8. A story of metformin-butyrate synergism to control various pathological conditions as a consequence of gut microbiome modification: Genesis of a wonder drug?

    Science.gov (United States)

    Maniar, Kunal; Moideen, Amal; Mittal, Ankur; Patil, Amol; Chakrabarti, Amitava; Banerjee, Dibyajyoti

    2017-03-01

    The most widely prescribed oral anti-diabetic agent today in the world today is a member of the biguanide class of drugs called metformin. Apart from its use in diabetes, it is currently being investigated for its potential use in many diseases such as cancer, cardiovascular diseases, Alzheimer's disease, obesity, comorbidities of diabetes such as retinopathy, nephropathy to name a few. Numerous in-vitro and in-vivo studies as well as clinical trials have been and are being conducted with a vast amount of literature being published every day. Numerous mechanisms for this drug have been proposed, but they have been unable to explain all the actions observed clinically. It is of interest that insulin has a stimulatory effect on cellular growth. Metformin sensitizes the insulin action but believed to be beneficial in cancer. Like -wise metformin is shown to have beneficial effects in opposite sets of pathological scenario looking from insulin sensitization point of view. This requires a comprehensive review of the disease conditions which are claimed to be affected by metformin therapy. Such a comprehensive review is presently lacking. In this review, we begin by examining the history of metformin before it became the most popular anti-diabetic medication today followed by a review of its relevant molecular mechanisms and important clinical trials in all areas where metformin has been studied and investigated till today. We also review novel mechanistic insight in metformin action in relation to microbiome and elaborate implications of such aspect in various disease states. Finally, we highlight the quandaries and suggest potential solutions which will help the researchers and physicians to channel their research and put this drug to better use.

  9. The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Nana Wang

    2016-01-01

    Full Text Available In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM patients. Tianmai Xiaoke Pian (TMXKP is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally was tested in T2DM rats (induced by a high-fat diet and streptozotocin. Eight weeks later, fasting blood glucose (FBG and oral glucose tolerance tests (OGTT were performed. Area under the curve (AUC and homeostatic model assessment of insulin resistance (HOMA-IR were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats P<0.05. Furthermore, we also observed that TMXKP could significantly decrease IRS-1, IRS-2, PI3-K p85α, and AKT2 gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levels P<0.05 in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

  10. Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety!

    Science.gov (United States)

    Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

    2016-07-01

    Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century. Like other biguanides, metformin can cause a lactic acidosis that is exceptionally rare but fatal. The likelihood of metformin-associated lactic acidosis is substantially higher in patients with kidney impairment and also among those with seemingly normal kidney function who are at risk of acute kidney injury (AKI). Hence, regulatory agencies in many industrialized nations have maintained strict renal restrictions surrounding metformin. However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m(2) who have not developed lactic acidosis. Thus, there clearly remains controversy in this area, and there has been heightened pressure to remove the renal restrictions of metformin. To provide a discussion on the pros and cons of relaxing the renal restrictions for metformin use, we provide a Point-Counterpoint. In the point narrative below, Drs. Kalantar-Zadeh and Kovesdy provide their argument that although there is little evidence of the potential benefits of metformin in kidney disease, just considering the sheer numbers of metformin users and the high fatality rate of its associated lactic acidosis, the most appropriate practice is to avoid metformin use in people with eGFR 30 mL/min/1.73 m(2)-William T. CefaluEditor in Chief, Diabetes Care.

  11. Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? Yes, They Should Be Relaxed! What's the Fuss?

    Science.gov (United States)

    Bakris, George L; Molitch, Mark E

    2016-07-01

    Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century. Like other biguanides, metformin can cause a lactic acidosis that is exceptionally rare but fatal. The likelihood of metformin-associated lactic acidosis is substantially higher in patients with kidney impairment and also among those with seemingly normal kidney function who are at risk of acute kidney injury (AKI). Hence, regulatory agencies in many industrialized nations have maintained strict renal restrictions surrounding metformin. However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m(2) who have not developed lactic acidosis. Thus, there clearly remains controversy in this area, and there has been heightened pressure to remove the renal restrictions of metformin. To provide a discussion on the pros and cons of relaxing the renal restrictions for metformin use, we provide a Point-Counterpoint. In the preceding point narrative, Drs. Kalantar-Zadeh and Kovesdy provide their argument that although there is little evidence of the potential benefits of metformin in kidney disease, just considering the sheer numbers of metformin users and the high fatality rate of its associated lactic acidosis, the most appropriate practice is to avoid metformin use in people with eGFR 30 mL/min/1.73 m(2)-William T. CefaluEditor in Chief, Diabetes Care.

  12. Biofilm-forming activity of bacteria isolated from toilet bowl biofilms and the bactericidal activity of disinfectants against the isolates.

    Science.gov (United States)

    Mori, Miho; Gomi, Mitsuhiro; Matsumune, Norihiko; Niizeki, Kazuma; Sakagami, Yoshikazu

    2013-01-01

    To evaluate the sanitary conditions of toilets, the bacterial counts of the toilet bowl biofilms in 5 Kansai area and 11 Kansai and Kanto area homes in Japan were measured in winter and summer seasons, respectively. Isolates (128 strains) were identified by analyzing 16S ribosomal RNA sequences. The number of colonies and bacterial species from biofilms sampled in winter tended to be higher and lower, respectively, than those in summer. Moreover, the composition of bacterial communities in summer and winter samples differed considerably. In summer samples, biofilms in Kansai and Kanto areas were dominated by Blastomonas sp. and Mycobacterium sp., respectively. Methylobacterium sp. was detected in all toilet bowl biofilms except for one sample. Methylobacterium sp. constituted the major presence in biofilms along with Brevundimonas sp., Sphingomonas sp., and/or Pseudomonas sp. The composition ratio of the sum of their genera was 88.0 from 42.9% of the total bacterial flora. The biofilm formation abilities of 128 isolates were investigated, and results suggested that Methylobacterium sp. and Sphingomonas sp. were involved in biofilm formation in toilet bowls. The biofilm formation of a mixed bacteria system that included bacteria with the highest biofilm-forming ability in a winter sample was greater than mixture without such bacteria. This result suggests that isolates possessing a high biofilm-forming activity are involved in the biofilm formation in the actual toilet bowl. A bactericidal test against 25 strains indicated that the bactericidal activities of didecyldimethylammonium chloride (DDAC) tended to be higher than those of polyhexamethylene biguanide (PHMB) and N-benzyl-N,N-dimethyldodecylammonium chloride (ADBAC). In particular, DDAC showed high bactericidal activity against approximately 90% of tested strains under the 5 h treatment.

  13. Coordination equilibria in the complex formation of guanylurea with CuII: Formation and stability of binary CuII-guanylurea and ternary CuII-guanylurea-glycinate complexes

    Indian Academy of Sciences (India)

    Tannistha Roy Barman; G N Mukherjee

    2008-07-01

    Combined pH-metric and spectrophotometric investigations on the complex formation equilibria of CuII with guanylurea (H$_{2}^{1}$NC(=O) 2NH.C(=3NH) 4NH2), hereafter, GuH, in the absence and in the presence of glycine (GlyH), in aqueous solution indicates variety of binary and mixed-ligand complexes: Cu(Gu)+, Cu(Gu)(OH); Cu(Gu)2, Cu(Gu-H)(Gu)-, Cu(Gu-H)$_{2}^{2-}$, Cu(Gu-H)(Gu-2H)3-; Cu(Gly)+, Cu(Gly) (OH); Cu(Gly)(Gu); Cu(Gly)(Gu-H)-, Cu(Gly)(Gu-2H)2-; (Gly)Cu(Gu)Cu(Gly)+, (Gly)Cu(Gu-H)Cu(Gly) and (Gly)Cu(Gu-2H)Cu(Gly)-. At pH < 6, guanylurea anion (Gu-) acts as a [(C=O), 3N-] or [=1NH, 3N-] bidentate ligand and above pH 7 it is transformed through a coordination equilibrium into a (=1N-, =3N-) bidentate ligand, similar to biguanide dianion. Occurrence of dinuclear complex species, (Gly) Cu(Gu)Cu(Gly)+, in the complexation equilibria, indicates bridging double bidentate [(1NH2, 3N-), (C=O, 4NH2)] and/or [(1NH2, 4NH2), (C=O, 3N-)] chelation by Gu- ion in an isomeric equilibrium. Above pH 6.5, the dinuclear complex decomposes mostly to the mononuclear species, Cu(Gly)(OH) and Cu(Gu)(OH) and only partly deprotonates to (Gly)Cu(Gu-H)Cu(Gly) and (Gly)Cu(Gu-2H)Cu(Gly)-. Electronic spectral shifts, with change of pH have been correlated with the possible modes of coordination of guanylurea species.

  14. A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme.

    Science.gov (United States)

    Elmaci, İlhan; Altinoz, Meric A

    2016-10-01

    Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a

  15. The origins of western obesity: a role for animal protein?

    Science.gov (United States)

    McCarty, M F

    2000-03-01

    A reduced propensity to oxidize fat, as indicated by a relatively high fasting respiratory quotient, is a major risk factor for weight gain. Increased insulin secretion works in various ways to impede fat oxidation and promote fat storage. The substantial 'spontaneous' weight loss often seen with very-low-fat dietary regimens may reflect not only a reduced rate of fat ingestion, but also an improved insulin sensitivity of skeletal muscle that down-regulates insulin secretion. Reduction of diurnal insulin secretion may also play a role in the fat loss often achieved with exercise training, low-glycemic-index diets, supplementation with soluble fiber or chromium, low-carbohydrate regimens, and biguanide therapy. The exceptional leanness of vegan cultures may reflect an additional factor - the absence of animal protein. Although dietary protein by itself provokes relatively little insulin release, it can markedly potentiate the insulin response to co-ingested carbohydrate; Western meals typically unite starchy foods with an animal protein-based main course. Thus, postprandial insulin secretion may be reduced by either avoiding animal protein, or segregating it in low-carbohydrate meals; the latter practice is a feature of fad diets stressing 'food combining'. Vegan diets tend to be relatively low in protein, legume protein may be slowly absorbed, and, as compared to animal protein, isolated soy protein provokes a greater release of glucagon, an enhancer of fat oxidation. The low insulin response to rice may mirror its low protein content. Minimizing diurnal insulin secretion in the context of a low fat intake may represent an effective strategy for achieving and maintaining leanness.

  16. Acanthamoeba polyphaga strain age and method of cyst production influence the observed efficacy of therapeutic agents and contact lens disinfectants.

    Science.gov (United States)

    Hughes, Reanne; Heaselgrave, Wayne; Kilvington, Simon

    2003-10-01

    The effects of age in culture and the type of medium used for induction of Acanthamoeba polyphaga (Ros) cysts on susceptibilities to polyhexamethylene biguanide (PHMB; 3 micro g/ml), chlorhexidine digluconate (30 micro g/ml), myristamidopropyl dimethylamine (20 micro g/ml), H(2)O(2) (3%), and two multipurpose contact lens solutions (MPS-1 and MPS-2, based on 1 micro g of PHMB per ml) were examined. Strain Ros-02 was cryopreserved on isolation in 1991, while strain Ros-91 had been in continuous axenic culture. Significant differences in susceptibilities to the disinfectants were found depending on the medium used for cyst preparation and the age of the test strain, with Ros-02 generally being more resistant. For example, the killing of Ros-91 cysts produced from an axenic culture of trophozoites in the presence of 50 mM MgCl(2) by MPS-2 was 4 logs, but the killing of Ros-02 by MPS-2 was only 2 logs (P < 0.05) and killing of both strains with cysts obtained from monoxenic cultures with Escherichia coli was only 1 log (P < 0.001). Assays repeated with different batches of the various cyst types gave consistent results. A batch of Ros-91 cysts stored at 4 degrees C and tested over an 8-week period with MPS-1 showed progressively increasing susceptibility to disinfection, although there was no loss of viability during storage (P < 0.01). These observations have important implications for the standardization and interpretation of Acanthamoeba disinfectant and therapeutic agent testing.

  17. Antiseptics and disinfectants for the treatment of bacterial vaginosis: A systematic review

    Directory of Open Access Journals (Sweden)

    Verstraelen Hans

    2012-06-01

    Full Text Available Abstract Background The study objective was to assess the available data on efficacy and tolerability of antiseptics and disinfectants in treating bacterial vaginosis (BV. Methods A systematic search was conducted by consulting PubMed (1966-2010, CINAHL (1982-2010, IPA (1970-2010, and the Cochrane CENTRAL databases. Clinical trials were searched for by the generic names of all antiseptics and disinfectants listed in the Anatomical Therapeutic Chemical (ATC Classification System under the code D08A. Clinical trials were considered eligible if the efficacy of antiseptics and disinfectants in the treatment of BV was assessed in comparison to placebo or standard antibiotic treatment with metronidazole or clindamycin and if diagnosis of BV relied on standard criteria such as Amsel’s and Nugent’s criteria. Results A total of 262 articles were found, of which 15 reports on clinical trials were assessed. Of these, four randomised controlled trials (RCTs were withheld from analysis. Reasons for exclusion were primarily the lack of standard criteria to diagnose BV or to assess cure, and control treatment not involving placebo or standard antibiotic treatment. Risk of bias for the included studies was assessed with the Cochrane Collaboration’s tool for assessing risk of bias. Three studies showed non-inferiority of chlorhexidine and polyhexamethylene biguanide compared to metronidazole or clindamycin. One RCT found that a single vaginal douche with hydrogen peroxide was slightly, though significantly less effective than a single oral dose of metronidazole. Conclusion The use of antiseptics and disinfectants for the treatment of BV has been poorly studied and most studies are somehow methodologically flawed. There is insufficient evidence at present to advocate the use of these agents, although some studies suggest that some antiseptics may have equal efficacy compared to clindamycin or metronidazole. Further study is warranted with special regard to

  18. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study

    Science.gov (United States)

    Inagaki, Nobuya; Kondo, Kazuoki; Yoshinari, Toru; Kuki, Hideki

    2015-01-01

    Aims/Introduction Canagliflozin is a sodium–glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes. Our aim was to examine its efficacy and safety as monotherapy or in combination with commonly used oral antihyperglycemic drugs in Japanese patients with type 2 diabetes. Materials and Methods Patients on diet/exercise alone or diet/exercise plus an oral antihyperglycemic drug (sulfonylurea, glinide, α-glucosidase inhibitor, biguanide, thiazolidinedione or dipeptidyl peptidase-4 inhibitor) were randomized to either 100 or 200 mg canagliflozin while continuing prior therapy. Patients were treated for 52 weeks in an open-label manner. Results Canagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose and bodyweight in all the study groups. Improvements were apparent by 4 weeks of treatment, and were maintained for 52 weeks. The reduction in hemoglobin A1c ranged from −0.80 to −1.06%, and from −0.93 to −1.26% in the 100 and 200 mg canagliflozin groups, respectively. Drug-related adverse events occurred in approximately one-third of patients, and included hypoglycemia/asymptomatic hypoglycemia and pollakiuria. Hypoglycemia/asymptomatic hypoglycemia was most common in patients treated with a sulfonylurea. Most adverse events were classified as mild or moderate in severity. Conclusions The results of the present study confirmed that treatment with canagliflozin resulted in significant reductions in glycemic control and bodyweight that were maintained for 52 weeks of treatment irrespective of whether it was administered as monotherapy or in combination with another oral antihyperglycemic drug. Canagliflozin was well tolerated, with a low incidence of drug-related adverse events. This trial was registered with ClinicalTrials.gov (no. NCT01387737). PMID:25802729

  19. 治疗2型糖尿病药物最新研究进展%Latest research progress of drugs for treating type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    杨彬

    2015-01-01

    Type 2 diabetes mellitus is an endocrine metabolic diseases with insulin resistance and relatively insufficient secretion of insulin caused by metabolism disorder of glucose, fat, and protein. Traditional oral hypoglycemic drugs included sulfonylureas, α-glucosidase inhibitor, biguanides, insulin sensitizer, and glinides. In recent years, with discovery of new mechanism, new drugs for type 2 diabetes mellitus have occurred, such as DDP-4 and GLP-1. This paper elaborates research progress of some other new drugs for type 2 diabetes mellitus, including type 2 sodium glucose co-transporters, 11β-HSD-1 inhibitor, GRP119, and PTP1B inhibitor.%2型糖尿病是一种因葡萄糖、脂肪、蛋白质代谢紊乱并最终导致胰岛素抵抗及胰岛素相对分泌不足的内分泌代谢疾病。传统口服降糖药物分别有磺脲类、α-葡糖糖苷酶抑制剂、双胍类、胰岛素增敏剂、格列奈类。近几年随着新的作用机制的发现,出现了多种治疗2型糖尿病的新型药物,如DDP-4和GLP-1。本文章主要阐述其他最新2型糖尿病治疗药物研究进展,包括输送器第二型抑制剂(SGLT2)、11β-HSD-1抑制剂、GRP119、PTP1B抑制剂。

  20. Recent progress in studying type 2 diabetes mellitus and tumor risk%2型糖尿病对肿瘤发生风险的研究新进展

    Institute of Scientific and Technical Information of China (English)

    陈月红; 杜亮; 张春林; 耿兴远; 刘关键

    2015-01-01

    [Summary] During recent years, increasing evidences have indicated that type 2 diabetes mellitus(T2DM) might increase the risk of certain tumors; the process might be not only related with the chronic pathologic status of T2DM such as hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, status of chronic inflammation but also associated with the long-term use of anti-diabetic drugs (i. e. sulfonylureas, biguanides, glitazones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptitide-1 receptor agonists), as well as the use of insulin and insulin analogues. Herewith a system review was made about the recent progress in studying T2DM and tumor risk.%近年来,越来越多的研究提示2型糖尿病会增加肿瘤发生风险,这除了与2型糖尿病具有高血糖、高胰岛素血症、胰岛素抵抗、血脂异常、持续的慢性炎症状态等病理特点相关外,还可能与糖尿病患者长期服用磺脲类药物、双胍类药物、格列酮类药物、二肽基肽酶Ⅳ抑制剂、胰升糖素样肽1受体激动剂等降糖药物和使用胰岛素与胰岛素类似物有关。本文就这些因素对肿瘤发生风险的影响进行综述。

  1. 用于2型糖尿病的两类药物

    Institute of Scientific and Technical Information of China (English)

    张宇

    2005-01-01

    2型糖尿病的特征是餐后和随后空腹出现高血糖(空腹血糖浓度高于125mg/dl)。高血糖是由于胰β-细胞分泌的胰岛素不足以补偿外周组织的胰岛素抗性。药物治疗的目的是控制血糖过多和最终避免组织与过高葡萄糖浓度持续接触有关的恶性并发症。然而,由于这种病的复杂性和胰β-细胞功能的不断衰退,2型糖尿病病人的血糖控制仍相当困难。因此,用现有的药物长期治疗仍不能充分控制血糖。这些药物包括减少肝葡萄糖产生、减少肠葡萄糖吸收和增加骨骼肌和脂肪对葡萄糖摄取的双胍类(biguanides);刺激胰β-细胞胰岛素分泌的SFU类;增强靶细胞对胰岛素应答、减少肝葡萄糖产生和增加骨骼肌和脂肪对胰岛素依赖性葡萄糖摄取的TZD类;刺激葡萄糖介导胰岛素分泌的megIitinide和D-苯丙氨酸(D-phenylalanine)衍生物;

  2. [Lactate acidosis: a rare or common disease?].

    Science.gov (United States)

    Kubát, K

    1995-05-01

    The authors present a survey of 50 documented cases of metabolic lactic acidosis (MLAC) recorded in the course of 5 years. To this study cases of severe hyperlactataemia (determined minimum lactate level of concentration 4 mmol/l) have been included. The sample consists of patients hospitalized at the Department of Internal Medicine Litomĕrice (hinterland of about 110,000 inhabitants). Liver involvement in 5 cases, cardiogenous shock in 6 cases, sepsis in 2 cases were the cause of lactic acidosis. The administration of biguanids (Adebit, Silubin R, Diformin) seems to be the probable cause in 21 cases, other cases were triggered by rarer causes. Dehydratation (16), vomiting (9), diarrhoea (11) dominate often in the clinical picture. The patients were admitted to the hospital often unconscious, with diagnose of vasculo-cerebral incidence, transitory ischaemic incidence... Quit rarely the typical Kussmaul's respiratory (only 9 cases) was recorded. Hyperlactatemia was usually associated with decrease of blood pH (theta = 7.12, pH less than 7.35 was recorded in 49 cases, pH less than 6.8 in 5 cases) and with decrease of BE value (= Ccoase, theta = -15.3 mmol/l). When the hypochloremia and/or hypocapnia was simultaneously more severe, only in these cases the value of pH was within physiological limits or even increased (10). The conclusions show that MLAC is not a rare disorder, however, its occurrence is depended rather on the clinician's capacity to diagnose this disorder and to indicate lactate examination. Usual signs of acidosis (Kussmaul's respiratory, decrease of pH, decrease of BE) can be missing in many cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Arterial stiffness, as monitored by cardio–ankle vascular index, is affected by obstructive sleep apnea, blood glucose control, and body weight – a case with 8 years follow up

    Science.gov (United States)

    Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Shirai, Kohji

    2016-01-01

    The cardio–ankle vascular index (CAVI) is an indicator of arterial stiffness from the heart to the ankles. The CAVI increases as arteriosclerosis progresses, but it can be decreased by appropriate treatment. There are several risk factors for coronary artery disease, however, the degree of stress caused by each separate risk factor to arteries cannot be assessed. CAVI increases with age and according to the severity of atherosclerosis. We found that CAVI also changes in response to the control of risk factors, which may be associated with the functional stiffness of arteries. CAVI can be a useful indicator of risk control for coronary artery disease. We followed a patient aged 71 years who had diabetes mellitus and obstructive sleep apnea (OSA) by measuring CAVI for 8 years from age 63. He underwent coronary artery bypass grafting due to angina pectoris when he was 63 years old. Before coronary artery bypass grafting, CAVI was 11.8 on the right and 11.5 on the left. Three years later he was found to have OSA and received treatment with continuous positive airway pressure. There was a marked improvement in CAVI after continuous positive airway pressure (age 68; right 10.4, left 10.2). However, following a gradual increase in body weight and worsening of diabetes mellitus, CAVI showed an increasing trend. CAVI decreased with biguanides treatment, but increased again with an increase in body weight. In conclusion, CAVI responded to the patient’s conditions including obesity, diabetes mellitus, and OSA. CAVI is not only a marker of arterial stiffness, but can also be a useful indicator of physiological status; it may be effective in total risk control for coronary artery disease. PMID:27563259

  4. Prescription factors associated with medication non-adherence in Japan assessed from leftover drugs in the SETSUYAKU-BAG campaign: Focus on oral antidiabetic drugs

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    Kaori Koyanagi

    2016-07-01

    Full Text Available Background: Medication adherence has an important influence on health outcomes in patients with chronic diseases. However, few studies have been performed in Japan to determine factors related to medication non-adherence. Objective: The aim of this study was to identify prescription factors related to medication non-adherence by investigating patient characteristics, all prescriptions, and prescriptions for oral antidiabetic drugs (OADs.Methods: A retrospective cross-sectional survey of prescription data about implementation of dosing regimen was performed at community pharmacies engaged in appropriate use of leftover drugs. We evaluated the amount of drugs originally prescribed and the reduced amount after use of leftover drugs, and then calculated prescription reduction ratio (PRR. We analyzed prescription factors contributing to non-adherence based on the PRR.Results: Prescription information for 1,207 patients was reviewed, revealing that patients were non-adherent to 58% of prescriptions. Lack of a drug copayment, fewer concurrent drugs, and drugs not in single-dose packaging were associated with non-adherence. Among the 1,207 patients, 234 prescriptions for diabetes and 452 OAD formulations were included. Forty-seven percent of prescriptions and 29% of the formulations were non-adherent. A higher dosing frequency and preprandial administration were associated with non-adherence. Among the OADs, adherence was lower for α-glucosidase inhibitors and biguanides than for sulfonylureas. Conclusions: Several factors related to patient characteristics, general drug prescriptions, and OAD prescriptions were associated with non-adherence. Further consideration will be needed to improve adherence to medication in Japan. Health care providers should perform more careful monitoring of adherence in patients with the factors identified by this study.

  5. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

    Science.gov (United States)

    Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R

    2014-11-01

    The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.

  6. Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System

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    MacLean Charles D

    2007-06-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptors (PPARs have emerged as important drug targets for diabetes. Drugs that activate PPARγ, such as the thiazolidinediones (TZDs, are widely used for treatment of Type 2 diabetes mellitus. PPARγ signaling could also play an anti-neoplastic role in several in vitro models, although conflicting results are reported from in vivo models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes. Methods A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs. Results In a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides, age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, P = 0.04. This association was particularly strong among patients using rosiglitazone (OR = 1.89, P = 0.02, and among women (OR = 2.07, P = 0.01. Conclusion These data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.

  7. Stratified medicine for the use of antidiabetic medication in treatment of type II diabetes and cancer: where do we go from here?

    Science.gov (United States)

    Emami-Riedmaier, A; Schaeffeler, E; Nies, A T; Mörike, K; Schwab, M

    2015-02-01

    At present, the global diabetes epidemic is affecting 347 million individuals, 90% of whom are diagnosed with type II diabetes mellitus (T2DM). T2DM is commonly treated with more than one type of therapy, including oral antidiabetic drugs (OADs) and agents used in the treatment of diabetic complications. Several pharmacological classes of OADs are currently available for the treatment of T2DM, of which insulin secretagogues (i.e. sulphonylureas and meglitinides), insulin sensitizers [thiazolidinediones (TZDs)] and biguanides are the most commonly prescribed. Although many of these OADs have been used for more than half a century in the treatment of T2DM, the pharmacogenomic characteristics of these compounds have only recently been investigated, primarily in retrospective studies. Recent advances in pharmacogenomics have led to the identification of polymorphisms that affect the expression and function of drug-metabolizing enzymes and drug transporters, as well as drug targets and receptors. These polymorphisms have been shown to affect the therapeutic response to and side effects associated with OADs. The aim of this review was to provide an up-to-date summary of some of the pharmacogenomic data obtained from studies of T2DM treatment, with a focus on polymorphisms in genes affecting pharmacokinetics, pharmacodynamics and treatment outcome of the most commonly prescribed OADs. In addition, the implications of pharmacogenomics in the use of the OAD metformin in cancer will be briefly discussed. Finally, we will focus on recent advances in novel 'omics' technologies and discuss how these might aid in the personalized management of T2DM.

  8. Effects of Formulation on Microbicide Potency and Mitigation of the Development of Bacterial Insusceptibility.

    Science.gov (United States)

    Cowley, Nicola L; Forbes, Sarah; Amézquita, Alejandro; McClure, Peter; Humphreys, Gavin J; McBain, Andrew J

    2015-10-01

    Risk assessments of the potential for microbicides to select for reduced bacterial susceptibility have been based largely on data generated through the exposure of bacteria to microbicides in aqueous solution. Since microbicides are normally formulated with multiple excipients, we have investigated the effect of formulation on antimicrobial activity and the induction of bacterial insusceptibility. We tested 8 species of bacteria (7 genera) before and after repeated exposure (14 passages), using a previously validated gradient plating system, for their susceptibilities to the microbicides benzalkonium chloride, benzisothiozolinone, chlorhexidine, didecyldimethyl ammonium chloride, DMDM-hydantoin, polyhexamethylene biguanide, thymol, and triclosan in aqueous solution (nonformulated) and in formulation with excipients often deployed in consumer products. Susceptibilities were also assessed following an additional 14 passages without microbicide to determine the stability of any susceptibility changes. MICs and minimum bactericidal concentrations (MBC) were on average 11-fold lower for formulated microbicides than for nonformulated microbicides. After exposure to the antimicrobial compounds, of 72 combinations of microbicide and bacterium there were 19≥4-fold (mean, 8-fold) increases in MIC for nonformulated and 8≥4-fold (mean, 2-fold) increases in MIC for formulated microbicides. Furthermore, there were 20≥4-fold increases in MBC (mean, 8-fold) for nonformulated and 10≥4-fold (mean, 2-fold) increases in MBC for formulated microbicides. Susceptibility decreases fully or partially reverted back to preexposure values for 49% of MICs and 72% of MBCs after further passage. In summary, formulated microbicides exhibited greater antibacterial potency than unformulated actives and susceptibility decreases after repeated exposure were lower in frequency and extent.

  9. Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic.

    Science.gov (United States)

    Hagi, Akifumi; Iwata, Koushi; Nii, Takuya; Nakata, Hikaru; Tsubotani, Yoshie; Inoue, Yasuhide

    2015-08-01

    Olanexidine gluconate [1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate] (development code OPB-2045G) is a new monobiguanide compound with bactericidal activity. In this study, we assessed its spectrum of bactericidal activity and mechanism of action. The minimal bactericidal concentrations of the compound for 30-, 60-, and 180-s exposures were determined with the microdilution method using a neutralizer against 320 bacterial strains from culture collections and clinical isolates. Based on the results, the estimated bactericidal olanexidine concentrations with 180-s exposures were 869 μg/ml for Gram-positive cocci (155 strains), 109 μg/ml for Gram-positive bacilli (29 strains), and 434 μg/ml for Gram-negative bacteria (136 strains). Olanexidine was active against a wide range of bacteria, especially Gram-positive cocci, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and had a spectrum of bactericidal activity comparable to that of commercial antiseptics, such as chlorhexidine and povidone-iodine. In vitro experiments exploring its mechanism of action indicated that olanexidine (i) interacts with the bacterial surface molecules, such as lipopolysaccharide and lipoteichoic acid, (ii) disrupts the cell membranes of liposomes, which are artificial bacterial membrane models, (iii) enhances the membrane permeability of Escherichia coli, (iv) disrupts the membrane integrity of S. aureus, and (v) denatures proteins at relatively high concentrations (≥160 μg/ml). These results indicate that olanexidine probably binds to the cell membrane, disrupts membrane integrity, and its bacteriostatic and bactericidal effects are caused by irreversible leakage of intracellular components. At relatively high concentrations, olanexidine aggregates cells by denaturing proteins. This mechanism differs slightly from that of a similar biguanide compound, chlorhexidine.

  10. Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer

    Science.gov (United States)

    Nangia-Makker, Pratima; Yu, Yingjie; Vasudevan, Anita; Farhana, Lulu; Rajendra, Sindhu G.; Levi, Edi; Majumdar, Adhip P. N.

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC) that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs). Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx), the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a) induce cell death in chemo resistant (CR) HT-29 and HCT-116 colon cancer cells, (b) inhibit colonospheres formation and (c) enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an effective treatment

  11. Metformin: a potential therapeutic agent for recurrent colon cancer.

    Directory of Open Access Journals (Sweden)

    Pratima Nangia-Makker

    Full Text Available Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs. Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx, the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a induce cell death in chemo resistant (CR HT-29 and HCT-116 colon cancer cells, (b inhibit colonospheres formation and (c enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼ 50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an

  12. Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I.

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    Simmy Thomas

    Full Text Available Verrucosidin (VCD belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78 expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose, but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin. However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin might act in a similar GRP78-independent fashion will be discussed.

  13. Uso del agente antimicrobiano PHMB para prevenir la infección de heridas The use of the antimicrobial agent PHMB to prevent wounds infection

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    Keith Moore

    2008-09-01

    Full Text Available La infección de heridas postoperatorias puede provocar una cicatrización tardía, una estancia prolongada en el hospital y mayores costes. El aumento de bacterias resistentes a los antibióticos es un factor en contra del uso profiláctico de los antibióticos. Una alternativa eficaz es el uso de antisépticos, que presentan menos probabilidades de generar resistencia. Los apósitos AMD TM usan polihexametileno biguanida (PHMB, que tiene una baja toxicidad para las células de las heridas y es eficaz para acabar con las bacterias resistentes a los antibióticos. En este artículo, se revisan las pruebas de la eficacia y rentabilidad de los apósitos AMD en la prevención de las infecciones en la herida quirúrgica si se usan de forma rutinaria en los protocolos estándar para el cuidado de heridas.Post-operative wound infections may result in delayed healing, extended hospital stay and increased costs. The increase in antibiotic-resistant bacteria mitigates against the prophylactic use of antibiotics. An effective alternative is the use of antiseptics that are less likely to generate resistance. AMD TM wound dressings use polyhexamethylene biguanide (PHMB which has a low toxicity for wound cells and is effective in killing antibiotic-resistant bacteria. This paper reviews the evidence for the efficacy and cost-effectiveness of AMD dressings in the prevention of surgical site infections when routinely used in standard wound care protocols.

  14. Type 2 Diabetes Mellitus: A Review of Current Trends

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    Abdulfatai B. Olokoba

    2012-07-01

    Full Text Available Type 2 diabetes mellitus (DM is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world. As a result of this trend, it is fast becoming an epidemic in some countries of the world with the number of people affected expected to double in the next decade due to increase in ageing population, thereby adding to the already existing burden for healthcare providers, especially in poorly developed countries. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include type 2 diabetes mellitus, prevalence, current diagnosis, and current treatment. Only articles in English were included. Screening and diagnosis is still based on World Health Organization (WHO and American Diabetes Association (ADA criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine. Inhaled insulin was licensed for use in 2006 but has been withdrawn from the market because of low patronage.

  15. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  16. Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-02-01

    Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b.w.) for 4 weeks. At the end of the treatment period, an array of biomarkers of oxidative stress were evaluated, including plasma antioxidant capacity measured in terms of ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (MDA), reduced glutathione (GSH), total plasma thiol (SH), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) in control and experimental groups. Metformin treatment resulted in an increase in FRAP, GSH, SH, and PMRS activities in both age groups compared to respective controls. On the other hand, treated groups exhibited significant reductions in ROS, MDA, PCO, AOPP, and AGE level. Save for FRAP and protein carbonyl, the effect of metformin on all other parameters was more pronounced in old-aged rats. Metformin caused a significant increase in the PMRS activity in young rats, however, the effect was less pronounced in old rats. These findings provide evidence with respect to restoration of antioxidant status in aged rats after short-term metformin treatment. The findings substantiate the putative antiaging role of metformin.

  17. To study the antihyperglycaemic and lipid lowering effect of garlic as an adjunct to metformin in patients of type 2 diabetes mellitus with obesity

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    Simran Chhatwal

    2012-02-01

    Full Text Available Background: Diabetes mellitus is a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia associated with disturbances of carbohydrate, fat and protein metabolism. The treatment constitutes lifestyle management, exercise, weight control and antihyperglycaemic drugs like sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, and meglitinide. Garlic has shown to have anti-hyperglycaemic and lipid lowering effects in various animal and human studies. Thus, this study was conducted to assess the antihyperglycaemic and lipid-lowering properties of Garlic in type2 diabetes patients with obesity. Methods: This was an open labelled prospective comparative study conducted on Type 2 diabetes mellitus patients with obesity where a total of 60 patients divided into two groups of 30 each (of either sex were enrolled. Group 1 was given Tab. metformin 500mg BD/TDS after meals. Group 2 was given Tab. metformin in a dose of 500mg BD/TDS after meals along with Cap. Garlic (Allium sativum 250mg BD. Patients were routinely investigated for fasting blood sugar, HbA1c and lipid profile i.e. Serum Cholesterol, HDL-C, Triglycerides and LDL-C at the start of the study. Patients were followed up at an interval of two weeks upto 12 weeks. Data obtained at the end of the study was statistically analysed using Student's- t test. Results: It was observed that both metformin and garlic reduced FBG and HbA1c significantly but percentage reduction in FBG was more with garlic but, change in HbA1c was not significant. Fall in total CHL, TG, LDL and an increase in HDL were more pronounced in patients treated with Garlic when given along with Metformin. Conclusions: Therefore, garlic showed better results as an antihyperglycaemic and lipid lowering agent. [Int J Basic Clin Pharmacol 2012; 1(1.000: 22-26

  18. Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues

    Indian Academy of Sciences (India)

    Najma Zaheer Baquer; Pardeep Kumar; Asia Taha; R K Kale; S M Cowsik; P McLean

    2011-06-01

    Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.

  19. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

    Science.gov (United States)

    Ortiz, Mario I

    2013-01-01

    BACKGROUND There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA. OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test. METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipizide, metformin or glibenclamide/metformin and glipizide/metformin combinations before the diclofenac and formaldehyde injections, and the effect on antinociception was assessed. Isobolograms of the combinations were constructed to test for a synergistic interaction. RESULTS: Systemic injection of diclofenac resulted in antinociception during the second phase of the test. Systemic pretreatment with the combinations of glibenclamide (0.56 mg/kg to 10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) and glipizide (0.56 mg/kg to10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) blocked DIA. The derived theoretical effective doses for 50% of subjects (ED50) for the glibenclamide/metformin and glipizide/metformin combinations were 32.52 mg/kg and 32.42 mg/kg, respectively, and were significantly higher than the actual observed experimental ED50 values (7.57 mg/kg and 8.43 mg/kg, respectively). CONCLUSION: Pretreatment with glibenclamide, glipizide or metformin blocked DIA in a dose-dependent manner, and combining either sulfonylurea with metformin produced even greater effects. The observed ED50s for the combinations were approximately fourfold lower than the calculated additive effects. These data indicate that sulfonylureas interact to produce antagonism of DIA. Combination therapy is a common second-line treatment for patients with diabetes and metabolic syndrome, a group that experiences pain from multiple sources. The results suggest that at least some anti-inflammatory agents may not be

  20. Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Ernest J Mui

    Full Text Available BACKGROUND AND METHODOLOGY: Toxoplasma gondii causes substantial morbidity, mortality, and costs for healthcare in the developed and developing world. Current medicines are not well tolerated and cause hypersensitivity reactions. The dihydrotriazine JPC-2067-B (4, 6-diamino-1, 2-dihydro-2, 2-dimethyl-1-(3'(2-chloro-, 4-trifluoromethoxyphenoxypropyloxy-1, 3, 5-triazine, which inhibits dihydrofolate reductase (DHFR, is highly effective against Plasmodium falciparum, Plasmodium vivax, and apicomplexans related to T. gondii. JPC-2067-B is the primary metabolite of the orally active biguanide JPC-2056 1-(3'-(2-chloro-4-trifluoromethoxyphenyloxypropyl oxy- 5-isopropylbiguanide, which is being advanced to clinical trials for malaria. Efficacy of the prodrug JPC-2056 and the active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as toxicity toward mammalian cells were tested. PRINCIPAL FINDINGS AND CONCLUSIONS: Herein, we found that JPC-2067-B is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM, inhibits the purified enzyme (IC50 6.5 nM, is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056 are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. SIGNIFICANCE: JPC-2056/JPC-2067-B have potential to be more effective and possibly less toxic treatments for toxoplasmosis than currently available medicines.

  1. Utilization study of antidiabetic agents in a teaching hospital of Sikkim and adherence to current standard treatment guidelines

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    Sushrut Varun Satpathy

    2016-01-01

    Full Text Available Objective: Diabetes has gradually emerged as one of the most serious public health problems in our country. This underlines the need for timely disease detection and decisive therapeutic intervention. This prospective cross-sectional observational study aims at analyzing the utilization pattern of antidiabetic agents in a remote North-East Indian tertiary care teaching hospital in the perspective of current standard treatment guidelines. Materials and Methods: Diabetic patients receiving antidiabetic medication, both as outpatients and inpatients in our hospital over a period of 12 months (May 2013–May 2014, were included in this study. The data obtained were sorted and analyzed on the basis of gender, type of therapy, and hospital setting. Results: A total of 310 patients were included in the study. Metformin was the single most frequently prescribed antidiabetic agent (66.8% followed by the sulfonylureas group (37.4%. Insulin was prescribed in 23.2% of the patients. Combination antidiabetic drug therapy (65.1% was used more frequently than monotherapy (34.8%. The use of biguanides (P < 0.0001 and sulfonylureas (P = 0.02 in combination was significant as compared to their use as monotherapy. A total of 48% of all antidiabetic combinations used, comprised metformin and sulfonylureas (n = 96. Insulin use was significantly higher as monotherapy and in inpatients (P< 0.0001. The utilization of drugs from the National List of Essential Medicines was 51.2%, while 11% of antidiabetics were prescribed by generic name. Conclusion: The pattern of utilization largely conforms to the current standard treatment guidelines. Increased use of generic drugs is an area with scope for improvement.

  2. Systematic review: Preventive and therapeutic applicationsof metformin in liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Metformin, a biguanide derivative, is the most commonlyprescribed medication in the treatment of type 2 diabetesmellitus. More recently, the use of metformin has shownpotential as a preventive and therapeutic agent for abroad spectrum of conditions, including liver diseaseand hepatic malignancies. In this systematic review,we critically analyze the literature behind the potentialuse of metformin across the spectrum of liver diseaseand malignancies. The PubMed and Ovid MEDLINEdatabases were searched from 2000 to March 2015,using a combination of relevant text words and MeSHterms: metformin and mammalian target of rapamycin,hepatitis B virus (HBV), hepatitis B virus (HCV), nonalcoholicfatty liver disease (NAFLD), hepatocellularcarcinoma (HCC) or cholangiocarcinoma. The searchresults were evaluated for pertinence to the issue ofmetformin in liver disease as well as for quality of studydesign. Metformin has a number of biochemical effectsthat would suggest a benefit in treating chronic liverdiseases, particularly in the context of insulin resistanceand inflammation. However, the literature thus far doesnot support any independent therapeutic role in NAFLDor HCV. Nonetheless, there is Level Ⅲ evidence fora chemopreventive role in patients with diabetes andchronic liver disease, with decreased incidence of HCCand cholangiocarcinoma. The use of metformin seemsto be safe in patients with cirrhosis, and provides asurvival benefit. Once hepatic malignancies are alreadyestablished, metformin does not offer any therapeuticpotential. In conclusion, there is insufficient evidence torecommend use of metformin in the adjunctive treatmentof chronic liver diseases, including NAFLD and HCV.However, there is good evidence for a chemopreventiverole against HCC among patients with diabetes andchronic liver disease, and metformin should be continuedin patients even with cirrhosis to provide this benefit.

  3. Metformin Induces Growth Inhibition and Cell Cycle Arrest by Upregulating MicroRNA34a in Renal Cancer Cells

    Science.gov (United States)

    Xie, Wei; Wang, Lei; Sheng, Halei; Qiu, Jing; Zhang, Di; Zhang, Le; Yang, Fan; Tang, Dahai; Zhang, Kebin

    2017-01-01

    Background Metformin is a widely used biguanide drug for the treatment of type 2 diabetes. It has been revaluated as a potential anti-cancer drug with promising activity in various tumors. However, the precise mechanisms underlying the suppression of cancer cells by metformin remain not well understood. Material/Methods In this study, human renal cell carcinoma cell line ACHN was used to investigate the anti-proliferation effect of metformin. A cell counting kit-8 assay was used to detect the cell viability. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of cyclin D1 and p27KIP1 was detected by Western blot. The underlying mechanism involving miRNA34a was further investigated by quantitative RT-PCR and transfection with miRNA inhibitor specific for miRNA34a in ACHN, 769-P, and A498 cells. Results Metformin could significantly inhibit the proliferation of ACHN cells in a dose- and time-dependent manner. In addition, the results showed that metformin induced G0/G1 phase arrest and delayed entry into S phase in ACHN cells. It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level. Furthermore, metformin increased ACHN cell death. Lastly, miRNA34a was found to be upregulated by metformin in ACHN, 769-P, and A498 cells. Subsequently, it was demonstrated that inhibition of miRNA34a could partially attenuate the suppressive effect of metformin on renal cancer cell proliferation. Conclusions The study data revealed that metformin induced cell growth inhibition and cell cycle arrest partially by upregulating miRNA34a in renal cancer cells. PMID:28045889

  4. PHARMACOTHERAPY BASED PROBLEMS WITH THE RECENT ADVANCES IN THE MANAGEMENT OF DIABETIS MELLITUS

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    LAKHAVAT SUDHAKAR

    2013-01-01

    Full Text Available Objectives : To review the drug treatments and some of the popular , non traditional remedies now available for type-2 diabetis mellitus, as well as selected investigational agents , to describe each medications place in the overal approach to treatment.Material and Methods : Data source from english language journals, pharmacolgy text books, abstracts, review articles and news paper accounts.Results :Older drugs like Sulfonyl ureas and Meglinitide analogues stimulate production and release of insulin.These drugs must be used in patients with intact pancreas and are associated with risk of hypoglycaemic .Biguanides (metformin reduces hepatic glucose production and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reaction like metallic taste and diarrhoea.Thiazolidinediones induce PPARץ which express relevant genes increase glucose transport and utilization.but the disadvantage is increased risk of cardiovascular problems.£ -glucosidase inhibitors inhibit enzymes £ -glucosidases present in the intestinal brush borders and there by prevent the absorption and delay the digestion of carbohydrates .Abdominal distension and diarrhea had restricted their use.Conclusion :. Hence there is continuous ongoing work in development of newer drugs ,which are safe ,efficacious and potent as well as free of undesirable effects such as sustained hypoglycemia. Fortunately there are newer drug , few of them approved while other still knocking the door from the classes of drug such as GLP1 Mimetic ,DPP-4 Inhibitors, SGLT-2 Inhibitors , insulin new class of drugs. Here we have tried to cover adverse effects and pharmacotherapy based problems in brief.

  5. Diabetes mellitus in dogs and cats: diagnosis and therapy

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    Mot, T.,

    2008-12-01

    Full Text Available Diabetes mellitus (DM is a disease of humans and animals, which causes increased levels of blood sugar (glucose. Normally,glucose is brought into the cells by a hormone - insulin.The cells then metabolize glucose to make energy used for all functions of the body. Animals suffering from DM either lack insulin, or the cells cannotuse the insulin that is there. As a result, blood glucose levels increase, and the cells have to use other substances for energy. When blood glucose levels become too high, glucose is found in the urine, causing increased frequency of urination and increased drinking. When blood glucose remains elevated over a period of time, other metabolic changes can occur, such as weight loss, acidosis, seizures, coma, blindness, cataracts, and nerve damage. Animals that are eating normally and not showing signs of illness may only require a blood or urine test to diagnose DM. Concurrent diseases (such as infection, Cushing’s disease, hyperthyroidism, pancreatitis, gastroenteritis, inflammatory bowel disease, hepatic lipidosis, or kidney disease make diabetes more difficult to diagnose and manage. A complete blood screen and other specific tests may be recommended to obtain the diagnosis and baseline values for treatment and future monitoring. The treatment for diabetes in dogs is similar to the treatment for diabetes in humans, through diet and insulin therapy. Dogs and cats with DM are usually treated with insulin. Insulin is a protein and, as such, not suitable for oral administration. Thus, it is administered once or several times daily by the subcutaneous route. Adjustment of the blood glucose concentration demands long hospital care, and subsequently the owner constantly has to keep a strict schedule at home. In veterinary practice the main groups of oral antidiabetic (used in human medicine either are: carbohydrate absorption inhibitors (e.g. acarbose; insulin sensitisers (biguanides such as metformin, thiazolidinedions

  6. New poly(ester urea) derived from L-leucine: Electrospun scaffolds loaded with antibacterial drugs and enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Díaz, Angélica; Valle, Luis J. del [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Tugushi, David; Katsarava, Ramaz [Institute of Chemistry and Molecular Engineering, Agricultural University of Georgia, 13 km. David Aghmashenebeli Alley, Tblisi 0131, Georgia (United States); Puiggalí, Jordi, E-mail: Jordi.Puiggali@upc.edu [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain)

    2015-01-01

    Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising materials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol-diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibroblast and epithelial cells. - Highlights: • Electrospun scaffolds from a biodegradable poly(ester urea) have been prepared. • Scaffolds were effectively loaded with bactericide agents. • Enzymatic degradability of the L-leucine derived poly(ester urea) was demonstrated. • Enzymes that accelerate degradation were incorporated in the electrospun fibers. • Cell adhesion/proliferation assays demonstrated

  7. Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Haruo, E-mail: hal.kato@gunma-u.ac.jp; Sekine, Yoshitaka; Furuya, Yosuke; Miyazawa, Yoshiyuki; Koike, Hidekazu; Suzuki, Kazuhiro

    2015-05-22

    Metformin is a biguanide drug that is widely used for the treatment of type 2 diabetes. Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo. The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF-1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of therapeutic value. Accordingly, we examined the effects of metformin on IGF-1R signaling in prostate cancer cells. Metformin significantly inhibited PC-3 cell proliferation, migration, and invasion. IGF-1R mRNA expression decreased significantly after 48 h of treatment, and IGF-1R protein expression decreased in a similar manner. IGF-1R knockdown by siRNA transfection led to inhibited proliferation, migration and invasion of PC-3 cells. IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment. In addition, intraperitoneal treatment with metformin significantly reduced tumor growth and IGF-1R mRNA expression in PC-3 xenografts. Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment. - Highlights: • Metformin inhibited PC-3 cell proliferation, migration, and invasion. • Metformin decreased IGF-1R mRNA and protein expressions in PC-3 cells. • Metformin inhibited IGF-1 induced ERK and Akt phosphorylations in PC-3 cells. • Metformin treatment inhibited PC-3 cell growth and IGF-1R expression in vivo. • Metformin may be a potent inhibitor of the IGF-1/IGF-1R signaling.

  8. Amputación corporal por accidente de trabajo en auxiliar de enfermería

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    Alexander Finol Muñoz

    2014-12-01

    Full Text Available Los auxiliares de enfermería son un rango profesional expuesto a múltiples riesgos por las actividades inherentes a su trabajo, expuestos constantemente a sustancias desinfectantes que sin el uso apropiado de equipos de protección individual, puede provocar efectos adversos y lesiones en el trabajador. Caso Clínico: Mujer de 51 años de edad, auxiliar de enfermería, con antecedentes de Diabetes Mellitus tipo I y Síndrome de Túnel Carpiano. Presenta derrame accidental de líquido mientras llenaba envase de Biguanid®, cayéndole en todo el cuerpo, por lo que decide cambiarse el uniforme entero, conservando calcetines y zapatos por el resto del turno. Posteriormente presenta lesiones en región dorsal de 4tº dedo de pie izquierdo, las cuales reciben tratamiento médico y seguimiento, con evolución tórpida, se evidencia edema y osteomielitis de la falange por lo que se decide amputar el dedo afectado. Una vez recuperada, fue estudiada con pruebas de provocación, evidenciando la susceptibilidad de la trabajadora a dicho desinfectante. Se propone al Instituto Nacional de Seguridad Social (INSS como accidente de trabajo y una indemnización por lesión permanente no invalidante, ambas peticiones con respuesta favorable para la trabajadora. Actualmente sigue desempeñando sus funciones como auxiliar en el hospital. El cumplimiento y vigilancia de las normas de prevención, basados en los riesgos laborales permitirá evitar este tipo de incidentes en la población laboral, evitando a largo plazo lesiones corporales, discapacidades y bajas laborales que alteran la calidad de vida del trabajador y de su entorno profesional.

  9. Fatal hemolytic anemia associated with metformin: A case report

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    Packer Clifford D

    2008-09-01

    Full Text Available Abstract Introduction Metformin is a widely prescribed biguanide antidiabetic drug that has been implicated as a cause of hemolytic anemia in three previous case reports. We report a case of rapidly fatal hemolysis that was temporally associated with the initiation of metformin treatment for diabetes. Clinicians need to be aware of this rare but potentially serious side effect of metformin. Case presentation A 56-year-old Caucasian man with type 2 diabetes mellitus was started on metformin to improve glycemic control. Shortly afterwards, he developed progressive fatigue, exertional dyspnea, cranberry-colored urine and jaundice. Laboratory studies showed severe hemolysis, with a drop in hemoglobin from 14.7 to 6.6 g/dl over 4 days, markedly elevated lactate dehydrogenase, bilirubin and reticulocyte counts, and a low haptoglobin level. A peripheral blood smear showed no schistocytes, and a direct Coombs test was positive for anti-IgG and negative for anti-C3. Despite corticosteroid treatment and transfusion of packed red blood cells, the patient developed increasing dyspnea, hypotension, further decline in hemoglobin to 3.3 g/dl, and fatal cardiorespiratory arrest 12 hours after admission. Conclusion The serologic findings in this case suggest an autoimmune hemolytic anemia, caused either by a drug-induced autoantibody or a warm autoantibody. Based on the temporal association with metformin and the lack of other clear precipitating causes, we propose that metformin-induced hemolysis with a drug-induced autoantibody is a strong possibility. This mechanism differs from a previously described case with a possible antibody to the erythrocyte-drug complex. It has been shown, however, that hemolysis may occur via multiple mechanisms from the same drug. Clinicians should consider the possibility of metformin-associated immune hemolytic anemia in patients with otherwise unexplained hemolysis.

  10. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus.

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    Antonella Napolitano

    Full Text Available Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM. These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i at baseline on metformin, (ii 7 days after stopping metformin, (iii when fasting blood glucose (FBG had risen by 25% after stopping metformin, and (iv when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1, peptide tyrosine-tyrosine (PYY and glucose-dependent insulinotropic peptide (GIP and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that

  11. 二甲双胍治疗青春期多囊卵巢综合征的疗效分析及安全性评价%The Clinical Effect and Safety of Metformin to Treat Polycystic Ovarian Syndrome

    Institute of Scientific and Technical Information of China (English)

    董业芳

    2015-01-01

    目的:评价二甲双胍治疗青春期多囊卵巢综合征的疗效和安全性。方法78例患者,分成两组,对照组患者进行优思明治疗,实验组患者进行优思明+二甲双胍治疗。结果实验组患者的多毛、痤疮等临床症状较对照组显著改善,T、LH、FSH、FINS、FPG、BMI指标较对照组显著下降(P<0.05)。结论在优思明治疗的基础上,应用二甲双胍治疗青春期多囊卵巢综合征效果显著,可以改善胰岛素抵抗,减少不良反应。%Objective To evaluate the efficacy and safety of metformin in the treatment of adolescent polycystic ovary syndrome. Methods 78 cases, 39 cases in each. control group were treated with Yasmin treatment, experimental group were Yasmin+dimethyl biguanide treatment. Results The clinical symptoms of patients in the experimental group of hirsutism, acne and other than in the control group improved signiifcantly, t, LH, FSH, fins, FPG, BMI group decreased significantly compared with the control group (P0.05. Conclusion Based Yasmin treatment , application of metformin in the treatment of adolescent polycystic ovary syndrome has better effects can improve insulin resistance and reduce the adverse reactions.

  12. Glycaemic control in patients with type 2 diabetes treated with oral antidiabetic drugs in urban areas of China%中国城市地区口服降糖药治疗的2型糖尿病患者血糖控制达标现状

    Institute of Scientific and Technical Information of China (English)

    陆菊明; 柳洁; 单忠艳; 杨玉芝; 胡仁明; 朱大龙; 杨立勇; 陈丽; 赵志刚; 李启富; 田浩明; 纪立农; 姬秋和; 刘静; 葛家璞; 时立新; 徐焱成; 郭晓蕙; 杨文英; 翁建平; 贾伟平; 邹大进; 周智广; 于德民

    2012-01-01

    )only in urban areas of China.Methods A total of 414 hospitals from 81 cities across China participated in the survey.Outpatients with T2DM on OADs treatment only were eligible for this study.General information of patients,medical history for T2DM,laboratory investigations and treatment regimen were collected from July to September in 2010.Logistic regression analysis was applied in the correlation analysis of glycemic control.Results A total of 97 315 eligible patients with T2DM were included in this study,with a mean age of (59 ± 11 ) years and a mean diabetes duration of (5 ±4) years.The mean glycated hemoglobin A1c (HbA1c) level of all patients was 7.7% ± 1.6%.Total of 35.1% (34 154 cases) and 17.9% ( 17 380 cases) of the patients had a HbA1 c < 7.0% and < 6.5%,respectively.Among all the patients,13.1% ( 12 748 cases) complicated with at least one macrovascular disease,and 15.1% ( 14 694 cases) with at least one microvascular disease. Of the patients with macrovascular complication ( s ),27.3% achieved optimal glycemic target (HbA1c < 7.0% ),it was lower than that in patients without macrovascular complication(s) (36.3% ).Similarly,25.2% of the patients with microvascular complication(s) achieved optimal glycemic target and it was lower than that in patients without microvascular complication (s)( 36.9% ).Among all the OAD treatment regimens,two kinds of OADs ( 51.3% ) and one OAD ( 34.5% )were most frequently used.It's found that 40.6%,33.7%,27.0% and 24.5% of the patients receiving one OAD,two OADs,three OADs and four or more OADs achieved glycemic control target,respectively.The most frequently used OADs were biguanides ( 30.8% ),sulphonylureas ( 24.6% ) and glinides (21.1%).Among the combined treatment regimens,23.7% were biguanides plus sulphonylureas,13.6%were biguanides plus glinides.Regression analysis showed that male,duration of diabetes,kinds of OADs,body mass index,combined with macro or micro

  13. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis.

    Science.gov (United States)

    Cufí, Silvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

    2010-11-15

    Transforming Growth Factor-b (TGFb) is a major driving force of the Epithelial-to-Mesenchymal (EMT) genetic program, which becomes overactive in the pathophysiology of many age-related human diseases.  TGFb-driven EMT is sufficient to generate migrating cancer stem cells by directly linking the acquisition of cellular motility with the maintenance of tumor-initiating (stemness) capacity.  Chronic diseases exhibiting excessive fibrosis can be caused by repeated and sustained infliction of TGFb-driven EMT, which increases collagen and extracellular matrix synthesis.  Pharmacological prevention and/or reversal of TGFb-induced EMT may therefore have important clinical applications in the management of cancer metastasis as well as in the prevention and/or treatment of end-state organ failures.  Earlier studies from our group have revealed that clinically-relevant concentrations of the biguanide derivative metformin, the most widely used oral agent to lower blood glucose concentration in patients with type 2 diabetes and metabolic syndrome, notably decreased both the self-renewal and the proliferation of trastuzumab-refractory breast cancer stem cell populations.  Given that: a.) tumor-initiating cancer stem cells display a significant enrichment in the expression of basal/mesenchymal or myoepithelial markers, including an increased secretion of TGFb; b.) metformin treatment impedes the ontogeny of generating the stem cell phenotype by transcriptionally repressing key drivers of the EMT genetic program (e.g. ZEB1, TWIST1, SNAIL2 [Slug], TGFbs), we recently hypothesized that prevention of TGFb-induced EMT might represent a common molecular mechanism underlying the anti-cancer stem cells and anti-fibrotic actions of metformin.  Remarkably, metformin exposure not only impedes TGFb-promoted loss of the epithelial marker E-cadherin in MCF-7 breast cancer cells but it prevents further TGF-induced cell scattering and accumulation of the mesenchymal marker vimentin in

  14. Analysis on Use of Hypoglycemic Drugs in Our Hospital during 2008-2010%2008-2010年我院降血糖药物用药分析

    Institute of Scientific and Technical Information of China (English)

    林国强; 沈斌

    2012-01-01

    Objective To investigate the current situation and the development trend of the hypoglycemic drugs used in our hospital to provide reference for the clinical application of antidiabetic drugs and its management. Methods The data of hypoglycemic drugs in the medical supply store were collected based on the used amount, defined daily dosages (DDDs) and the sums of money for statistical analysis during 2008 - 2010. Results The average annual increasing rate of the consumption amount of antidiabetic drugs was 40% during these three years. Acarbose occupied the first place in the list of the sum of consumption money and DDDs. Sulfonylureas and biguanides were most commonly used hypoglycemic drugs in clinic during successive 3 years, accounting for 32% of the total value of DDDs in whole antidiabetic drugs. The first line of antidiabetic drugs included metformin, gliclazide, acarbose, glipizide and insulin. Conclusion The used amounts of hypoglycemic drugs are gradually increased with the increase of diabetic patients year by year. Therefore, more attention should be paid to the curative effects and safety in medication.%目的 为降血糖药物的临床应用和管理提供参考.方法 对2008年至2010年医院药库出库的降血糖药物使用金额、用药频度(DDDs)、用药金额、各年度DDDs前10位药物等进行统计分析.结果 3年间降血糖药物销售金额年平均增长率为40%.销售金额及DDDs居首位的是阿卡渡糖,磺酰脲类和双胍类连续3年为临床主要使用的降血糖药物,占所有降血糖药物DDDs总值的32%;二甲双胍、格列齐特、阿卡波糖、格列美脲、胰岛素等为临床一线用药.结论 降血糖药物的用量随着糖尿病患者的增加逐年增长,因此临床用药应注意药物疗效及安全性.

  15. Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena.

    Science.gov (United States)

    Martin-Castillo, Begoña; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Menendez, Javier A

    2010-03-15

    In the early 1970s, Professor Vladimir Dilman originally developed the idea that antidiabetic biguanides may be promising as geroprotectors and anticancer drugs ("metabolic rehabilitation").  In the early 2000s, Anisimov´s experiments revealed that chronic treatment of female transgenic HER2-/neu mice with metformin significantly reduced the incidence and size of mammary adenocarcinomas and increased the mean latency of the tumors.  Epidemiological studies have confirmed that metformin, but not other anti-diabetic drugs, significantly reduces cancer incidence and improves cancer patients' survival in type 2 diabetics.  At present, pioneer work by Dilman & Anisimov at the Petrov Institute of Oncology (St. Petersburg, Russia) is rapidly evolving due to ever-growing preclinical studies using human tumor-derived cultured cancer cells and animal models. We herein critically review how the antidiabetic drug metformin is getting reset to metabolically fight cancer. Our current perception is that metformin may constitute a novel "hybrid anti-cancer pill" physically combining both the long-lasting effects of antibodies -by persistently lowering levels of blood insulin and glucose- and the immediate potency of a cancer cell-targeting molecular agent -by suppressing the pivotal AMPK/mTOR/S6K1 axis and several protein kinases at once, including tyrosine kinase receptors such as HER1 and HER2-.  In this scenario, we discuss the relevance of metformin doses in pre-clinical models regarding metformin's mechanisms of action in clinical settings. We examine recent landmark studies demonstrating metformin's ability to specifically target the cancer-initiating stem cells from which tumor cells develop, thereby preventing cancer relapse when used in combination with cytotoxic chemotherapy (dandelion hypothesis).  We present the notion that, by acting as an efficient caloric restriction mimetic, metformin enhanced intrinsic capacity of mitotically competent cells to self

  16. The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling.

    Science.gov (United States)

    Scherbakov, Alexander M; Sorokin, Danila V; Tatarskiy, Victor V; Prokhorov, Nikolay S; Semina, Svetlana E; Berstein, Lev M; Krasil'nikov, Mikhail A

    2016-04-01

    Metformin, a biguanide antidiabetic drug, is used to decrease hyperglycemia in patients with type 2 diabetes. Recently, the epidemiological studies revealed the potential of metformin as an anti-tumor drug for several types of cancer, including breast cancer. Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Nevertheless, some patients can be non-sensitive or resistant to metformin action. Here we analyzed the mechanism of the formation of metformin-resistant phenotype in breast cancer cells and its role in estrogen receptor (ER) regulation. The experiments were performed on the ER-positive MCF-7 breast cancer cells and metformin-resistant MCF-7 subline (MCF-7/M) developed due to long-term metformin treatment. The transcriptional activity of NF-κB and ER was measured by the luciferase reporter gene analysis. The protein expression was determined by immunoblotting (Snail1, (phospho)AMPK, (phospho)IκBα, (phospho)mTOR, cyclin D1, (phospho)Akt and ERα) and immunohistochemical analysis (E-cadherin). We have found that: 1) metformin treatment of MCF-7 cells is accompanied with the stimulation of AMPK and inhibition of growth-related proteins including IκBα, NF-κB, cyclin D1 and ERα; 2) long-term metformin treatment lead to the appearance and progression of cross-resistance to metformin and tamoxifen; the resistant cells are characterized with the unaffected AMPK activity, but the irreversible ER suppression and constitutive activation of Akt/Snail1 signaling; 3) Akt/Snail1 signaling is involved into progression of metformin resistance. The results presented may be considered as the first evidence of the progression of cross-resistance to metformin and tamoxifen in breast cancer cells. Importantly, the acquired resistance to both drugs is based on the

  17. Current management of diabetes mellitus and future directions in care.

    Science.gov (United States)

    Chatterjee, Sudesna; Davies, Melanie J

    2015-11-01

    The last 90 years have seen considerable advances in the management of type 1 and type 2 diabetes. Prof MacLean of Guy's Hospital wrote in the Postgraduate Medical Journal in 1926 about the numerous challenges that faced patients and their healthcare professionals in delivering safe and effective diabetes care at that time. The discovery of insulin in 1922 heralded a new age in enabling long-term glycaemic control, which reduced morbidity and mortality. Thirty years later, the first oral agents for diabetes, the biguanides and sulfonylureas, appeared and freed type 2 patients from having to inject insulin following diagnosis. Improvements in insulin formulations over the decades, including rapid-acting and long-acting insulin analogues that more closely mimic physiological insulin secretion, have increased the flexibility and efficacy of type 1 diabetes management. The last two decades have seen major advances in technology, which has manifested in more accurate glucose monitoring systems and insulin delivery devices ('insulin pump'). Increased understanding of the pathophysiological deficits underlying type 2 diabetes has led to the development of targeted therapeutic approaches such as on the small intestine (glucagon-like peptide-1 receptor analogues and dipeptidyl-peptidase IV inhibitors) and kidneys (sodium-glucose cotransporter-2 inhibitors). A patient-centred approach delivered by a multidisciplinary team is now advocated. Glycaemic targets are set according to individual circumstances, taking into account factors such as weight, hypoglycaemia risk and patient preference. Stepwise treatment guidelines devised by international diabetes organisations standardise and rationalise management. Structured education programmes and psychological support are now well-established as essential for improving patient motivation and self-empowerment. Large multicentre randomised trials have confirmed the effectiveness of intensive glycaemic control on microvascular

  18. Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation

    Directory of Open Access Journals (Sweden)

    Sabatini Mary E

    2011-05-01

    Full Text Available Abstract Background Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function. Methods We utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization (progesterone production in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype. Conclusions Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their

  19. Antimicrobial efficacy assessment of multi-use solution to disinfect hydrophilic contact lens, in vitro Avaliação da ação antimicrobiana de soluções multiuso para desinfecção de lentes de contato hidrofílicas, in vitro

    Directory of Open Access Journals (Sweden)

    Aline Cristina Fioravanti Lui

    2009-10-01

    Full Text Available PURPOSE: To evaluate the efficacy of disinfecting solutions in hydrophilic contact lenses (CL. METHODS: Two multi-use solutions denominated solution A (0.001% polyquaternium-1 and 0.0005% myristamidopropyl dimethylamine and solution B (0.0001% polyaminopropyl biguanide were used. The solutions were tested in hydrophilic contact lenses infected with Pseudomonas aeruginosa (ATCC27583, Staphylococcus epidermidis (ATCC1226, Klebsiella pneumoniae (ATCC13883, Staphylococcus aureus (ATCC25923 and Candida albicans (ATCC 10231 and the decrease in microorganisms growth after the hydrophilic contact lenses were cleaned with the respective solutions was verified. The manufacture's instructions were followed. RESULTS: A decrease of 90% of Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus, Candida albicans and a decrease 100% of Klebsiella pneumoniae was observed. CONCLUSION: The solutions decreased the amount of microorganisms tested.OBJETIVO: Avaliar a influência da ação antimicrobiana das soluções multiuso para desinfecção de lentes de contato hidrofílicas. MÉTODOS: Duas soluções multiuso denominadas solução A (poliquaternário-1 a 0,001% e miristamidopropil dimetilamina a 0,0005% e solução B (poliaminopropil biguanida a 0,0001% foram testadas em lentes de contato hidrofílicas contaminadas com Pseudomonas aeruginosa (ATCC27583, Staphylococcus epidermidis (ATCC1226, Klebsiella pneumoniae (ATCC13883, Staphylococcus aureus (ATCC25923 e Candida albicans (ATCC 10231 para verificar a quantidade de redução do crescimento dos microrganismos após o enxágue com as soluções. Foram seguidas as instruções preconizadas pelos fabricantes. RESULTADOS: Houve redução de 90% do crescimento de Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus e Candida albicans. Não houve crescimento de Klebsiella pneumoniae. CONCLUSÃO: As soluções testadas neste trabalho mostraram redução do número de

  20. Predictors of mortality subsequent to a fracture in diabetes mellitus patients

    Directory of Open Access Journals (Sweden)

    Jakob eStarup-Linde

    2015-04-01

    Full Text Available Background: Type-1 and type-2 Diabetes Mellitus (DM is associated with an increased fracture risk and possibly an increased risk of death following a fracture.Aim: To investigate the association between diabetes related drugs and mortality following a fracture. Methods: A nested case-control study was conducted. Cases were patients with DM who died following a fracture; controls were DM patients not dying after a fracture. We identified DM patients using the Danish National Hospital Discharge Register (1977-2011 and included information on date of DM diagnosis, date of fracture and comorbidities. From the Danish Cause of Death Register the date of death was collected (2008-2011. From the Central Region of Jutland, Denmark, medication use was collected (2008-2011. Analysis was performed by unconditional logistic regression.Results: 2,621 diabetes patients with a fracture following the diabetes diagnosis and with information on medication use were included. Of these 229 died. In a multivariate analysis, statin use (n= 1,106 (42% statin users, odds ratio (OR = 0.60, 95 % confidence interval, p=0.012 decreased the risk of dying subsequent to a fracture. Male gender (OR=1.57, p=0.005, increasing age (OR=1.08, p<0.001, a diagnosis of retinopathy (OR=2.12, p=0.008, heart failure (OR= 1.68, p=0.004 and use of glucocorticoids (OR=2.22, p=0.001 were associated with an increased risk of death. None of the antidiabetics; biguanides, glucagon-like receptor agonists, β-cell stimulants, glitazones, and insulin were associated with mortality.Conclusion: Co-morbidity reflected by late onset complications, heart failure and glucocorticoid use was associated with an increased risk of mortality subsequent to a fracture. Statin use may reduce mortality subsequent to a fracture in diabetes patients. Clinical trials are needed to determine whether diabetes patients with a fracture should initiate statin treatment.

  1. Behavior of Listeria monocytogenes in a multi-species biofilm with Enterococcus faecalis and Enterococcus faecium and control through sanitation procedures.

    Science.gov (United States)

    da Silva Fernandes, Meg; Kabuki, Dirce Yorika; Kuaye, Arnaldo Yoshiteru

    2015-05-04

    The formation of mono-species biofilm (Listeria monocytogenes) and multi-species biofilms (Enterococcus faecium, Enterococcus faecalis, and L. monocytogenes) was evaluated. In addition, the effectiveness of sanitation procedures for the control of the multi-species biofilm also was evaluated. The biofilms were grown on stainless steel coupons at various incubation temperatures (7, 25 and 39°C) and contact times (0, 1, 2, 4, 6 and 8 days). In all tests, at 7°C, the microbial counts were below 0.4 log CFU/cm(2) and not characteristic of biofilms. In mono-species biofilm, the counts of L. monocytogenes after 8 days of contact were 4.1 and 2.8 log CFU/cm(2) at 25 and 39°C, respectively. In the multi-species biofilms, Enterococcus spp. were present at counts of 8 log CFU/cm(2) at 25 and 39°C after 8 days of contact. However, the L. monocytogenes in multi-species biofilms was significantly affected by the presence of Enterococcus spp. and by temperature. At 25°C, the growth of L. monocytogenes biofilms was favored in multi-species cultures, with counts above 6 log CFU/cm(2) after 8 days of contact. In contrast, at 39°C, a negative effect was observed for L. monocytogenes biofilm growth in mixed cultures, with a significant reduction in counts over time and values below 0.4 log CFU/cm(2) starting at day 4. Anionic tensioactive cleaning complemented with another procedure (acid cleaning, disinfection or acid cleaning+disinfection) eliminated the multi-species biofilms under all conditions tested (counts of all micro-organisms<0.4 log CFU/cm(2)). Peracetic acid was the most effective disinfectant, eliminating the multi-species biofilms under all tested conditions (counts of the all microorganisms <0.4 log CFU/cm(2)). In contrast, biguanide was the least effective disinfectant, failing to eliminate biofilms under all the test conditions.

  2. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes.

    Science.gov (United States)

    Fisman, Enrique Z; Tenenbaum, Alexander

    2015-01-01

    The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50% of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25%. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase 4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials--notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years--did not show an increased risk for ischemic

  3. Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system.

    Science.gov (United States)

    Machado, Daniele G; Bettio, Luis E B; Cunha, Mauricio P; Capra, Juliano C; Dalmarco, Juliana B; Pizzolatti, Moacir G; Rodrigues, Ana Lúcia S

    2009-06-15

    Rosemary, Rosmarinus officinalis L. (Labiatae) has several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including depression. In this study, the effect of the hydroalcoholic extract of the stems and leaves of this plant was investigated in two behavioral models, the forced swimming test (FST) and tail suspension test (TST) in mice. The extract of R. officinalis produced an antidepressant-like effect, since the acute treatment of mice with the extract by p.o. route significantly reduced the immobility time in the FST (100 mg/kg) and TST (10-100 mg/kg), as compared to a control group, without accompanying changes in ambulation in the open-field test. Moreover, the repeated administration (14 days) of the hydroalcoholic extract of R. officinalis by p.o. route also produced an antidepressant-like effect in the TST (100-300 mg/kg). The pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A) receptor antagonist), 1-(m-chlorophenyl) biguanide (mCPBG, 10 mg/kg, i.p., a 5-HT(3) receptor agonist), prazosin (1 mg/kg, i.p., an alpha(1-)adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), but not yohimbine (1 mg/kg, i.p., an alpha(2-)adrenoceptor antagonist) was able to reverse the anti-immobility effect of the extract (10 mg/kg, p.o.) in the TST. The combination of MDL72222, (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist) with a sub-effective dose of the extract of R. officinalis (1 mg/kg, p.o.) produced an anti-immobility effect in the TST. The results suggest that the antidepressant action of the extract of R. officinalis is mediated by an interaction with the monoaminergic system and that this plant should be further investigated as an alternative

  4. Research on the fixation performance of chitosan and it 's derivative%壳聚糖及其衍生物的固色性能研究

    Institute of Scientific and Technical Information of China (English)

    雷宁宁; 钟娜; 施亦东

    2014-01-01

    The fixing performance of chitosan hydrochloride (CSH) with different molecular weight and chitosan biguanide hydrochloride (CSGH) as a fixing agent for cotton fabric dyed with reactive dyes was discussed. The results showed that the fixing effects of CSH on reactive dyes were related to its molecular weight, and the CSH with high molecular weight (HMW) exhibited better fixing effects than that with low molecular weight (LMW). The CSGH molecule has positive charges and the imino groups, which could further strengthened the interaction among the CSGH, dyes and cellulose molecules. After treated by the CSGH, the soaping, perspiration and dry rubbing fastness of the dyed fabrics could be increased 0.5~1 grade, while the wet rubbing fastness of ones was also improved obviously. The infrared spectrum (FTIR) of the dyed fabric treated by CSGH showed that a cross-linking was formed among CSGH, dyes and cellulose molecules.%研究了不同分子质量壳聚糖盐酸盐和壳聚糖双胍盐酸盐对活性染料染色棉织物固色性能的影响。结果发现,壳聚糖盐酸盐的固色效果与其分子质量有关,高分子质量壳聚糖比低分子质量有更好的固色效果,壳聚糖双胍盐酸盐由于引入了更多的阳电荷和亚氨基,增强了壳聚糖双胍盐、染料和纤维分子之间的相互作用。因此,经过壳聚糖双胍盐固色后的棉织物,其皂洗、汗渍和摩擦牢度提高了0.5~1级,湿摩擦牢度改善更为明显。通过红外光谱分析,壳聚糖双胍盐酸盐与纤维和染料之间形成了交联。

  5. Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Higurashi Takuma

    2012-03-01

    Full Text Available Abstract Background Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF. ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients. Methods/Design This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation. Discussion This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with

  6. Opportunistic amoebae: challenges in prophylaxis and treatment.

    Science.gov (United States)

    Schuster, Frederick L; Visvesvara, Govinda S

    2004-02-01

    polyhexamethylene biguanide, in combination with propamidine isothionate (Brolene), hexamidine (Désomodine), or neomycin. Acanthamoeba spp. may also be carriers of endosymbiotic bacteria (Legionella and Legionella-like pathogens) and have been implicated in outbreaks of pneumonias in debilitated hosts. As with other infectious diseases, recovery is dependent not only on antimicrobial therapy, but also on patient's immune status, infective dose and virulence of the ameba strain, and on how early the disease is diagnosed and drug therapy initiated.

  7. Treatment Differences and Clinical Characteristics of Polycystic Ovarian Syndrome Between Yi and Han Nationality in Liangshan Yi Autonomous Prefecture%凉山州彝族、汉族多囊卵巢综合征患者的特点及治疗差异性

    Institute of Scientific and Technical Information of China (English)

    李雅琪; 宋致蓉; 廖国芳; 张瑜; 马燕; 彭俊; 杨炜婷

    2012-01-01

    Objective To discuss treatment differences and clinical characteristics between Yi and Han nationality in Liangshan Yi Autonomous Prefecture with polycystic ovarian syndrome (PCOS). Methods From January 2009 to December 2011, a total of 80 cases with PCOS were included into this study. They were divided into Yi group (n = 40) and Han group (n = 40) according to their nationalities. The study protocol was approved by the Kthical Review Board of Investigation in Human Being of First People s Hospital of Liangshan Prefecture. Informed consent was obtained from each participate. There had no significant differences between two groups among age, infertility years, and so on (P>0. 05). All the subjects received dimethyl biguanide + metformin hydrochloride for 3 months, and the glycometabolism indexes, body mass index (BMI) , and egg chamber changes were observed before and after the treatment. Results The level of LH, T and LH/FSH ratio decreased significantly than those before treatment (P0.05).对两组患者给予炔雌醇环丙孕酮(达英-35)+二甲双胍治疗3个月,观察治疗前、后性激素及糖代谢指标、体重指数(BMI)、卵泡变化情况等.结果 彝族组及汉族组黄体生成素(LH),睾酮(T),卵泡刺激素(FSH)及LH/FSH水平均较治疗前明显下降(P<0.05),治疗后两组葡萄糖和胰岛素的曲线下面积(AUC)均明显下降(P<0.05).结论炔雌醇环丙孕酮+二甲双胍对降低PCOS患者内分泌代谢紊乱疗效明显,但彝、汉族之间临床表现及疗效有一定差异.

  8. II型糖尿病及口服降糖药物综述%Type 2 Diabetes and Oral Antihyperglycemic Drugs

    Institute of Scientific and Technical Information of China (English)

    孙广田; 李娟娟

    2015-01-01

    Ⅱ型糖尿病主要是由于环境或者遗传引起的内源性疾病,因其高昂的治疗费用及难于根治而成为摆在全世界卫生组织和各政府面前的一道难题。Ⅱ型糖尿病的治疗已经乏力几十年了,至今还没有一个安全的单独治疗药物的出现。现有的口服降血糖药物大致可以分为磺酰脲类药物、双胍类药物、葡萄糖苷酶、氯茴苯酸类药物,DPP-4抑制剂和噻唑烷二酮类药物,但这些药物的安全性和疗效值得关注。在这篇文章里,我们分析了这六种药物的优缺点,讨论几种治疗Ⅱ型糖尿病新型药物的趋势。%Type II diabetes is a heterogeneous disease where environment and genetics are important factors for the expression of the disease.The high cost for treating complications of diabetes is a burden for public health systems and governments worldwide. Type II diabeteshas been causing debilitation worldwide for many decades, and a single drug that safely treats the disease has yet to be discovered.Sulfonylureas, biguanides, α-glucosidase, meglitinides, DPP-4 inhibitors and thiazolidinediones are among the classes of oral hypoglycemicdrugs available to treat Type II diabetes, but concerns exist regarding safety and efficacy of these drugs. In this article we presentthe pros and cons of the six classes and discuss some of the latest advances towards the development of new drugs for the treatment ofType II diabetes.

  9. 黄连温胆汤对2型糖尿病小鼠血糖的影响%Study of Huanglian Wendan Tang to T2MD Mouse Blood Sugar Influence

    Institute of Scientific and Technical Information of China (English)

    张卫华; 刘华东; 刘舟; 黄仕文

    2011-01-01

    Objective: Study Huanglian Wendan Tang to the obese diabetes mouse empty stomach blood sugar and Sugar tolerance influence. Method: The mouse feeds the high thermal feed 4 weeks later, Abdominal cavity injection STZ, Divides into five groups stochastically, Gives two armor biguanide 250mg/kg of Masculine control group, Huanglian Wendan Tang Low, middle and high monitoring group, Gives separately Huanglian Wendan Tang 5,l0,20g/kg. Gives the medicine 3 weeks continuously. Result:Huanglian Wendan Tang Obviously reduces diabetes mouse FBG, AUC of Huanglian Wendan Tang high monitoring group is lower than the model group obviously 25.6%. Conclusion: Huanglian Wendan Tang has obviously falls the blood sugar function of STZ induction T2MD mouse.%目的:研究黄连温胆汤对2型糖尿病小鼠空腹血糖、糖耐量的影响.方法:小鼠喂养高糖、高脂、高热量饲料4周后,腹腔注射链脲佐菌素( STZ) 100mg/kg,制备糖尿病小鼠模型,随机分为二甲双胍阳性对照组,模型对照组,黄连温胆汤低、中、高剂量组.黄连温胆汤低、中、高剂量组,分别给黄连温胆汤5、10、20g/kg(按生药量计).阳性药组给予二甲双胍250mg/kg.连续给药3周.结果:黄连温胆汤显著降低糖尿病小鼠FBG,黄连温胆汤(20g,/kg)的抑制率为33.1%;口服葡萄糖溶液(29/kg)模型组小鼠的血糖值均较空白组高,与模型组相比,黄连温胆汤( 20g/kg)能显著降低小鼠的血糖水平(P<0.05);黄连温胆汤高剂量组糖耐量曲线下面积(AUC)明显低于模型组25.6%.结论:黄连温胆汤对于STZ诱导的2型糖尿病小鼠具有显著的降血糖作用.

  10. Analysis of Hypoqlycemic Drug Use in Hospitalized Patients with Diabetes Mellitus%糖尿病住院患者降糖药应用分析

    Institute of Scientific and Technical Information of China (English)

    丁全; 陈世才

    2013-01-01

    Objective:To analyze the hypoqlycemic drug use in hospitalized patients with diabetes mel itus , providing reference for rational drug use in our hospital. Methods:We col ected and analyzed data of Hypoglyoemic drug use and related adverse reactions by retrospective analysis in hospitalized patients with diabetes mel itus in our hospital from June 2011 to June 2012. Result:In this ananlysis ,we included 365 patients, The most commonly used drug was insulin, fol owed by biguanides. The proportion of two-drug combination therapy was the highest, fol owed by triple therapy and monotherapy.Of 365 patients adverse events occurred in 96 patients, hypoglycemic occurred in 27 patients . Conclusions:Hypoglycemic drug use in hospitalized patients is rational. However, the education of the patients by clinical pharmacist is not enough. The clinical pharmacist should take an active part in education of the patients, promote rational and ef ective use of drugs so that the risk caused by adverse reactions can be reduced.%  目的:对我院内分泌糖尿病患者降糖药应用情况进行调查分析,为临床合理用药提供参考。方法:查阅我院2011年6月至2012年6月内分泌科病历,采用回顾性分析法,设计调查表格,对降糖药使用情况进行调查,将所得数据用Excel 2000软件进行统计分析。结果:382例患者应用降血糖药物,应用最多的是胰岛素,其次是双胍类药物;两药联合治疗的比例最高,其次为三药治疗;96例患者发生不良反应,其中低血糖反应27例。结论:我院内分泌病区糖尿病患者降血糖药物应用比较合理,但临床药师对患者的用药教育还比较欠缺,充分发挥临床药师作用,有利于降血糖药物的合理应用,并减少不良反应的发生。

  11. Progress of research on antimicrobial agents and their application to textiles%抗菌防霉剂的研究进展及其在纺织品中的应用

    Institute of Scientific and Technical Information of China (English)

    郑皓; 徐少俊; 杨晓霞; 陈志龙

    2011-01-01

    This paper introduced the development of both domestic and overseas research of inorganic, organic and natural antimicrobial agents and their application to textiles, including antimicrobial agents of metal ionic, TiO2 photocatalytic oxides, metal / photocatalytic oxides nano-composite, inorganic/organic composite, biguanide compounds, N-halamine, phenylic acids, quaternary ammonium salts, quaternary phosphonium salts, and natural antimicrobial agents such as chitosan and its derivatives, with emphasis on quaternary ammonium salts and quaternary phosphonium salts. In addition, the antimicrobial treating methods for textiles were classified into polyblending, chemical modification of fiber, conjugate spinning, fiber finishing and textile finishing. The test methods for antimicrobial efficiency and safety of the agents were reviewed and the future development of antimicrobial agents was given.%介绍了国内外无机、有机、天然抗菌防霉剂的研究进展以及其在纺织品上的应用.具体包括金属离子型抗菌剂,TiO2等光催化氧化型抗菌剂,金属离子光催化氧化物型复合纳米抗菌剂,有机-无机复合抗菌剂,双胍类、卤代胺类、苯酚、季铵盐类、季鳞盐类等有机抗菌剂,壳聚糖及其衍生物等天然抗菌剂.着重介绍了季铵和季鳞盐类有机抗菌剂.对纤维和纺织品抗菌处理方法进行了分类,有共混纺丝法、纤维化学改性法、复合纺丝法、纤维整理法、纺织品后整理法.对抗菌防霉性及安全性检测方法进行了概述,并对抗菌剂的发展进行了展望.

  12. Clinical research on treating Xiaoke Yinxu Zaore plus Yu syndrome with the Xiaoke Ping decoction%消渴平汤治疗消渴阴虚燥热兼瘀证的临床研究

    Institute of Scientific and Technical Information of China (English)

    周景妍

    2015-01-01

    Objective: To investigate clinical effects of the Xiaoke Ping decoction on Xiaoke Yinxu Zaore plus Yu syndrome. Methods: 40 patients with Xiaoke Yinxu Zaore plus Yu syndrome were randomly divided to the observation group and the control group, 20 cases for each group. The control group received biguanide sustained-release tablets. The observation group received the Xiaoke Ping decoction. 4 weeks for a course. During the treatment, clinical efficacy in two groups were observed. Results: The clinical symptoms in two groups were improved. The main symptoms, signs, physical and chemical inspection in the observation group were better than that in the control group. The total efficiency in the treatment group was higher. Conclusion: The Xiaoke Ping decoction was effective on Xiaoke Yinxu Zaore plus Yu syndrome, and worthy of promotion.%目的:分析消渴平汤对消渴阴虚燥热兼瘀证的治疗效果。方法:收集40例消渴阴虚燥热兼瘀证患者,随机分为观察组和对照组,每组各20例。对照组患者使用口服盐酸二甲双胍缓释片进行治疗,观察组患者口服消渴平汤进行治疗,4周为一个疗程,在治疗过程中观察患者的治疗效果。结果:两组患者的临床症状均有好转,但是观察组患者在主要症状、患者体征以及理化检查方面比对照组患者明显要好,同时观察组患者的总有效率也明显比对照组患者要高。结论:在对消渴阴虚燥热兼瘀证患者治疗的过程中,使用消渴平汤能够更好的对患者进行治疗,同时治疗效果以及治疗总有效率也明显比使用传统盐酸二甲双胍缓释片进行治疗的患者高,在实际对消渴阴虚燥热兼瘀证患者治疗的过程中值得推广应用。

  13. DPP -4抑制剂治疗糖尿病的临床疗效%Effect of DPP 4 inhibitors in treating diabetic

    Institute of Scientific and Technical Information of China (English)

    张淑萍

    2016-01-01

    目的:探讨 DPP -4抑制剂治疗糖尿病的临床疗效。方法选取2013年3月—2015年3月晋中市第一人民医院收治的84例糖尿病患者,分为对照组和观察组,每组42例。对照组患者接受双胍类(二甲双胍)药物治疗,观察组患者在对照组基础上接受 DPP -4抑制剂(西格列汀)治疗。比较两组患者的临床疗效及不良反应发生情况。结果观察组患者空腹血糖(FPG)、餐后2h 血糖(2hPG)及糖化血红蛋白(HbA1c )低于对照组,总有效率高于对照组,不良反应发生率低于对照组,差异有统计学意义(P ﹤0.05)。结论 DPP -4抑制剂治疗糖尿病的临床疗效显著,不良反应少,安全性高。%Objective To study the effect of DPP 4 inhibitors in treating diabetic. Methods A total of 84 diabetic patients were selected in the First People’s Hospital of Jinzhong from March 2013 to March 2015,they were divided into observa-tion group and control group,42 cases in each group. Control group were treated with biguanides( metformin),observation group were treated with DPP 4 inhibitors(sitagliptin phosphate). Effect and incidence of adverse between the two groups were compared. Results Fasting blood - glucose(FPG),2 hour postprandial blood glucose(2hPG)and glycosylated hemoglobin (HbA1c )of observation group were lower than control group,total effective rate was higher than control group,incidence of ad-verse reaction was lower than control group,the differences were statistically significant(P ﹤ 0. 05). Conclusion DPP 4 in-hibitors has significant effect in treating diabetic,has less adverse reactions and high safty.

  14. Effect of Sitagliptin and Metformin on Prediabetes Progression to Type 2 Diabetes - A Randomized, Double-Blind, Double-Arm, Multicenter Clinical Trial: Protocol for the Sitagliptin and Metformin in PreDiabetes (SiMePreD) Study

    Science.gov (United States)

    2016-01-01

    Background The high prevalence and incidence of type 2 diabetes mellitus (DM), and its associated morbidity and mortality, has prompted growing international interest and effort in the primary prevention of this disease. Primary prevention is possible since type 2 DM is preceded by prediabetes, offering a window opportunity to treat patients, and prevent the emergence of advanced disease. Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing beta cell function and increases beta cell mass. These two effects have been demonstrated both in vitro and in animal studies, and current clinical data show that sitagliptin is safe. Metformin, a biguanide, reduces insulin resistance and inhibits hepatic gluconeogenesis, and has an excellent safety profile. The combination of metformin and sitagliptin, targeting both characteristics of prediabetes (insulin resistance and progressive beta cell degeneration), may potentially slow or halt the progression from prediabetes to type 2 DM. This paper describes the rationale and design of the Sitagliptin and Metformin in PreDiabetes (SiMePreD) study. Objective The aim of this study is to determine the effect of sitagliptin and metformin on progression from prediabetes to type 2 DM. The objectives of the study are to determine the effects of metformin and placebo on glycemic endpoints, the effects of sitagliptin and metformin on glycemic endpoints, the effects of metformin and placebo on incidence of cardiovascular disease and death, and the effects of sitagliptin and metformin on incidence of cardiovascular disease and death. Methods This is a randomized, double-blind, multicenter clinical study that will determine if the combination of metformin and sitagliptin is effective in preventing the progression from prediabetes to type 2 DM. The study will contain two arms (metformin/sitagliptin and metformin/placebo). Primary endpoints include the number of subjects progressing from prediabetes to type 2 DM, the

  15. Association between glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with cardiovascular complications

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    Huri HZ

    2015-08-01

    Full Text Available Hasniza Zaman Huri,1,2 Doris Yew Hui Ling,1 Wan Azman Wan Ahmad2,3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Clinical Investigation Centre, University Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia; 3Cardiology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Purpose: Cardiovascular disease (CVD is a macrovascular complication in patients with type 2 diabetes mellitus (T2DM. To date, glycemic control profiles of antidiabetic drugs in cardiovascular (CV complications have not been clearly elucidated. Therefore, this study was conducted retrospectively to assess the association of antidiabetic drugs and glycemic control with CV profiles in T2DM patients. The association of concurrent medications and comorbidities with glycemic control was also investigated.Methods: A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated.Results: Sulfonylureas in combination (P=0.002 and sulfonylurea monotherapy (P<0.001 were found to be associated with good glycemic control, whereas insulin in combination (P=0.051, and combination biguanides and insulin therapy (P=0.012 were found to be associated with poor glycemic control. Stroke (P=0.044 was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026, elderly patients (P=0.018, low-density lipoprotein cholesterol levels (P=0.021, and fasting plasma glucose (P<0.001 were found to be significantly correlated with good glycemic control

  16. A novel 5HT3 antagonist 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide) prevents diabetes-induced depressive phenotypes in mice: Modulation of serotonergic system.

    Science.gov (United States)

    Gupta, Deepali; Thangaraj, Devadoss; Radhakrishnan, Mahesh

    2016-01-15

    Despite the presence of a multitudinous pharmacotherapy, diabetes-induced depressive disorder remains undertreated. Evidence suggests that brain serotonergic deficits are associated with depressive-like behavior in diabetes and that 5HT3 receptor (5HT3R) antagonists have serotonergic facilitatory effects. This study examined the effects of a novel 5HT3R antagonist, 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide), in diabetes-induced depressive phenotypes. Experimentally, (1) to evaluate the effects of 4i, mice with 8-weeks of diabetes (induced by streptozotocin, 200mg/kg, i.p.) were treated with vehicle, 4i (0.5 and 1mg/kg/day, i.p.), fluoxetine (10mg/kg/day, i.p.) for 4-weeks and subjected to neurobehavioral assays, followed by biochemical estimation of serotonin levels in midbrain, prefrontal-cortex and cerebellum. (2) To evaluate the role of 5HT3R in the postulated effect of 4i, diabetic mice were given 4i (1mg/kg/day, i.p.) after 1h of 1-(m-chlorophenyl)-biguanide (mCPBG, a 5HT3R agonist, 10mg/kg/day, i.p.) treatment and subjected to the same protocol. The results showed that diabetic mice exhibited a significant behavioral deficit, including depression-like behavior in forced swim test, anxiety-like in open field test and sociability deficits in social interaction test, along with a significant decrease in serotonin level in these brain regions. 4i (1mg/kg), similar to fluoxetine, prevented these behavioral abnormalities and normalized brain serotonin levels. 4i (0.5mg/kg) ameliorated only diabetes-induced depressive-like behavior and serotonin deficits, but not anxiety-like effects. mCPBG blunted 4i-mediated behavioral response and increase in brain serotonin levels. Altogether, this study suggests that 4i prevents diabetes-induced depressive phenotypes in mice, which may involve antagonism of 5HT3Rs and increase in serotonin levels in discrete brain regions.

  17. Relationship of plasma creatinine and lactic acid in type 2 diabetic patients without renal dysfunction

    Institute of Scientific and Technical Information of China (English)

    LIU Fang; LU Jun-xi; TANG Jun-ling; LI Li; LU Hui-juan; HOU Xu-hong; JIA Wei-ping; XIANG Kun-san

    2009-01-01

    Background As one of most widely-used biguanides,metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low.However,lactic acidemia induced by mefformin was reported in patients without renal dysfunction.It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors.This study aimed to clarify the influencing factors of lactic acid,and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function.Methods The clinical data and venous blood samples of 1024 type 2 diabetic patients treated with(n=426)or without metformin(n=599)were collected.The lactic acid was assayed by enzyme-electrode method.The biochemical indexes included creatinine(Cr)and hepatase were measured with enzymatic procedures.The lactic acid concentrations of different Cr subgroups were compared,and the correlation and receiver operating characteristic curve analysis were used.Results The mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group(P<0.01),but no lactic acidosis was found in all patients.The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr,metformin,alanine transferase(ALT),body mass index(BMI),Urine albumin(Ualb),and blood urea nitrogen(BUN)in total patients;and Cr,ALT,BMI and BUN in non-metformin treated patients;Cr and ALT in metformin-group.The lactate concentration increased with the increment of Cr levels,and reached its peak at Cr 111-130 μmol/L,and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 μmol/L.Conclusions Metformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction.Cr,ALT,and BMI are independent associated factors of blood lactic acid levels.There is low proportion of lactatemia in

  18. In Vitro Anti-Echinococcal and Metabolic Effects of Metformin Involve Activation of AMP-Activated Protein Kinase in Larval Stages of Echinococcus granulosus.

    Science.gov (United States)

    Loos, Julia A; Cumino, Andrea C

    2015-01-01

    Metformin (Met) is a biguanide anti-hyperglycemic agent, which also exerts antiproliferative effects on cancer cells. This drug inhibits the complex I of the mitochondrial electron transport chain inducing a fall in the cell energy charge and leading 5'-AMP-activated protein kinase (AMPK) activation. AMPK is a highly conserved heterotrimeric complex that coordinates metabolic and growth pathways in order to maintain energy homeostasis and cell survival, mainly under nutritional stress conditions, in a Liver Kinase B1 (LKB1)-dependent manner. This work describes for the first time, the in vitro anti-echinococcal effect of Met on Echinococcus granulosus larval stages, as well as the molecular characterization of AMPK (Eg-AMPK) in this parasite of clinical importance. The drug exerted a dose-dependent effect on the viability of both larval stages. Based on this, we proceeded with the identification of the genes encoding for the different subunits of Eg-AMPK. We cloned one gene coding for the catalytic subunit (Eg-ampkɑ) and two genes coding for the regulatory subunits (Eg-ampkβ and Eg-ampkγ), all of them constitutively transcribed in E. granulosus protoscoleces and metacestodes. Their deduced amino acid sequences show all the conserved functional domains, including key amino acids involved in catalytic activity and protein-protein interactions. In protoscoleces, the drug induced the activation of AMPK (Eg-AMPKɑ-P176), possibly as a consequence of cellular energy charge depletion evidenced by assays with the fluorescent indicator JC-1. Met also led to carbohydrate starvation, it increased glucogenolysis and homolactic fermentation, and decreased transcription of intermediary metabolism genes. By in toto immunolocalization assays, we detected Eg-AMPKɑ-P176 expression, both in the nucleus and the cytoplasm of cells as in the larval tegument, the posterior bladder and the calcareous corpuscles of control and Met-treated protoscoleces. Interestingly, expression of Eg

  19. In Vitro Anti-Echinococcal and Metabolic Effects of Metformin Involve Activation of AMP-Activated Protein Kinase in Larval Stages of Echinococcus granulosus.

    Directory of Open Access Journals (Sweden)

    Julia A Loos

    Full Text Available Metformin (Met is a biguanide anti-hyperglycemic agent, which also exerts antiproliferative effects on cancer cells. This drug inhibits the complex I of the mitochondrial electron transport chain inducing a fall in the cell energy charge and leading 5'-AMP-activated protein kinase (AMPK activation. AMPK is a highly conserved heterotrimeric complex that coordinates metabolic and growth pathways in order to maintain energy homeostasis and cell survival, mainly under nutritional stress conditions, in a Liver Kinase B1 (LKB1-dependent manner. This work describes for the first time, the in vitro anti-echinococcal effect of Met on Echinococcus granulosus larval stages, as well as the molecular characterization of AMPK (Eg-AMPK in this parasite of clinical importance. The drug exerted a dose-dependent effect on the viability of both larval stages. Based on this, we proceeded with the identification of the genes encoding for the different subunits of Eg-AMPK. We cloned one gene coding for the catalytic subunit (Eg-ampkɑ and two genes coding for the regulatory subunits (Eg-ampkβ and Eg-ampkγ, all of them constitutively transcribed in E. granulosus protoscoleces and metacestodes. Their deduced amino acid sequences show all the conserved functional domains, including key amino acids involved in catalytic activity and protein-protein interactions. In protoscoleces, the drug induced the activation of AMPK (Eg-AMPKɑ-P176, possibly as a consequence of cellular energy charge depletion evidenced by assays with the fluorescent indicator JC-1. Met also led to carbohydrate starvation, it increased glucogenolysis and homolactic fermentation, and decreased transcription of intermediary metabolism genes. By in toto immunolocalization assays, we detected Eg-AMPKɑ-P176 expression, both in the nucleus and the cytoplasm of cells as in the larval tegument, the posterior bladder and the calcareous corpuscles of control and Met-treated protoscoleces. Interestingly

  20. Anagliptin in the treatment of type 2 diabetes: safety, efficacy, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Nishio S

    2015-03-01

    Full Text Available Shinya Nishio, Mariko Abe, Hiroyuki ItoDepartment of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital Higashikoiwa, Edogawa-ku, Tokyo, JapanAbstract: Anagliptin is a novel dipeptidyl peptidase-4 inhibitor that has been available in Japan since 2012. Because anagliptin is not generally used in countries other than Japan, there are only a small number of reports investigating the effects of anagliptin. In the present article, we review the safety and efficacy of anagliptin according to data obtained from preclinical trials and postmarketing studies. The usual dose of anagliptin is 200 mg daily, and increases in the dose up to 400 mg daily have been approved in cases in which the blood glucose–lowering effect is insufficient. In a Phase II trial, the reduction in the HbA1c values from baseline after 12 weeks monotherapy with 200 mg and 400 mg of daily anagliptin was 0.75%±0.50% and 0.82%±0.46%, respectively, and more than 40% of the subjects receiving anagliptin at a dose of 200 mg or 400 mg daily achieved an HbA1c level below 6.9%. Furthermore, the levels of HbA1c, fasting blood glucose, and postprandial blood glucose were significantly decreased at 52 weeks compared with the baseline values in a Phase III trial investigating the effects of anagliptin included in combination therapy with other oral antidiabetic agents. In a pooled analysis of Phase II and Phase II/III trials, the goal achievement rates for an HbA1c level below 7.0% at 12 weeks were 40.3%, 39.4%, 30.0%, and 34.8% in the patients treated with anagliptin combined with α-glucosidase inhibitors, thiazolidinediones, sulfonylureas, and biguanides, respectively. Meanwhile, the serum lipid concentrations significantly improved after the administration of anagliptin in a pooled analysis of Phase III trials, and no serious adverse effects have been reported in preclinical trials. Therefore, the use of anagliptin in patients with type 2 diabetes is considered to be safe and

  1. Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

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    Huri HZ

    2015-08-01

    Full Text Available Hasniza Zaman Huri,1,2 Lay Peng Lim,1 Soo Kun Lim3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, 2Clinical Investigation Centre, University Malaya Medical Centre, 3Renal Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established.Purpose: This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD.Patients and methods: This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7% or poor glycemic control (A1C ≥7% based on the recommendations of the American Diabetes Association.Results: Majority of the patients presented with CKD stage 4 (43.4%. Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9% was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%. Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001, insulin therapy (P=0.005, and combination of biguanides with insulin (P=0.038 were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004, comorbidities such as anemia (P=0.024 and retinopathy (P=0.033, concurrent medications such as erythropoietin therapy (P=0.047, a-blockers (P=0.033, and antigouts (P=0.003 were also correlated with A1C.Conclusion: Identification of

  2. The DiabCare Asia 2008 study – Outcomes on control and complications of type 2 diabetic patients in Indonesia

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    Pradana Soewondo

    2010-11-01

    Full Text Available Aim: To collect information on diabetes management, diabetes complications, and awareness of self-control in diabetic population of the country. This study also evaluated the physician perspectives, psychological aspects, and quality of life of diabetic patients.Methods: This was a non-interventional, cross-sectional study, which recruited 1832 patients from secondary and tertiary medical centers across Indonesia. Data on demography, medical history, risk factors and clinical examination reports including laboratory assessments were collected from medical records of patients. Blood samples of all patients were collected for centralized HbA1c measurements.Results: Among 1832 patients, 1785 individuals were eligible for analysis. The mean age of the patients was 58.9+9.6 years. The mean duration of diabetes was 8.5+7.0 years. Majority (97.5% of the patients had type 2 diabetes. 67.9% had poor control of diabetes (A1c:8.1 ± 2.0%. 47.2% had FPG>130 mg/dL (161.6±14.6 mg/dL. Dyslipidemia was reported in 60%  (834/1390 and 74% (617/834 of those received lipid lowering treatment. Neuropathy was most common  complication (63.5%; other complications were: Diabetic retinopathy 42%, nephropathy 7.3%, severe late complications 16.9%, macrovascular complications 16%, microvascular complications 27.6%. About 81.3% of patients were on OADs (± insulin, 37.7% were on insulin (±OADs. Majority used biguanides followed by sulfonylureas. Human insulin was used by 73.2%, premix regimen 58.5%, analogues usage was 24.9%. Majority of the WHO-5 well being index responses fell in positive territoryConclusion: Poor glycaemic control in majority of patients is a concern. There is a need for a large proportion of patients to be adjusted to more intensive pharmacotherapy and a multi-disciplinary approach for management should be adopted. The study fi ndings should be communicated to policymakers and physicians to help them provide proper healthcare and its facilities in

  3. 2型糖尿病合并牙周炎经强化治疗后的牙周状况探讨%Investigation of the Periodontal Status in Patients with Type 2 Diabetes Complicated by Periodontitis after Intensive Treatment

    Institute of Scientific and Technical Information of China (English)

    岳建荣; 张萱

    2014-01-01

    目的:研究分析强化治疗2型糖尿病伴有牙周炎后的牙周情况。方法选择2013年9月—2014年9月期间在该院接受治疗的76例糖尿病合并牙周炎患者,应用随机双盲法将其平均分成对照组(应用双胍类、磺脲类降血糖药物进行治疗)与研究组(应用胰岛素强化治疗),每组各有患者38例。结果研究组患者的血糖、血脂、糖化血红蛋白(英简HbA 1c)等指标明显优于对照组;并且,探诊深度、龈沟出血的改善程度明显优于对照组,差异有统计学意义(P<0.05)。结论强化治疗2型糖尿病合并牙周炎取得了满意疗效,能明显改善牙周状况。%Objective To study and analyze the periodontal status in patients with type 2 diabetes complicated by periodontitis af-ter intensive treatment. Methods 76 patients with diabetes complicated by periodontitis treated in our hospital from September 2013 to September 2014 were selected and equally divided into the control group (application of biguanides, sulfonylurea hypo-glycemic drugs for treatment) and the study group(application of insulin for intensive treatment) with 38 patients in each according to the random double blind method. Results The blood glucose, blood lipid, glycosylated hemoglobin (HbA1c) and other indexes of the study group were significantly better than those of the control group;in addition, the improvement in probing depth and sulcus bleeding of the study group was obviously better than that of the control group, the difference had statistical significance, P<0.05. Conclusion For patients with type 2 diabetes complicated by periodontitis, intensive treatment can achieve satisfactory effect and improve the periodontal status significantly.

  4. Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study

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    Sindt CW

    2012-03-01

    Full Text Available Christine W Sindt1, Trudy K Grout1, D Brice Critser1, Jami R Kern2, David L Meadows21University of Iowa Hospitals and Clinics, Iowa City, IA; 2Alcon Research Ltd, Fort Worth, TX, USABackground: The purpose of this study was to assess whether differences in central corneal dendritic immune cell densities associated with combinations of soft contact lenses and lens care solutions could be detected by in vivo confocal microscopy.Methods: Participants were adults naïve to contact lens wear (n = 10 or who wore soft contact lenses habitually on a daily-wear schedule (n = 38 or on a study-assigned schedule for 30 days with daily disposable silicone hydrogel lenses (n = 15. Central corneas were scanned using an in vivo confocal microscope. Cell densities were compared among groups by demographic parameters, lens materials, and lens care solutions (polyhexamethylene biguanide [PHMB], polyquaternium-1 and myristamidopropyl dimethylamine [PQ/MAPD], peroxide, or blister pack solution [for daily disposable lenses].Results: Among lens wearers, no associations were observed between immune cell densities and age, gender, or years of lens-wearing experience. Mean cell density was significantly lower (P < 0.01 in nonwearers (29 ± 23 cells/mm2, n = 10 than in lens wearers (64 ± 71 cells/mm2, n = 53. Mean cell density was lower (P = 0.21 with traditional polymer lenses (47 ± 44 cells/mm2, n = 12 than with silicone hydrogel lenses (69 ± 77 cells/mm2, n = 41. Lowest to highest mean density of immune cells among lens wearers was as follows: PQ/MAPD solution (49 ± 28 cells/mm2, blister pack solution (63 ± 81 cells/mm2, PHMB solution (66 ± 44 cells/mm2, and peroxide solution (85 ± 112 cells/mm2.Conclusion: In this pilot study, in vivo confocal microscopy was useful for detecting an elevated immune response associated with soft contact lenses, and for identifying lens-related and solution-related immune responses that merit further research.Keywords: Clear Care

  5. ACTION OF NEWER DISINFECTANTS ON MULTIDRUG RESISTANT BACTERIA

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    Bipasa

    2014-03-01

    Full Text Available BACKGROUND: Current procedures for infection control in hospital environments have not been successful in curbing the rise in infections by multi-drug-resistant (MDR pathogens. Emergence of resistance to chemical disinfectants is increasing steadily and has been reported worldwide. So prevention of multidrug-resistant health care associated infections (HAI has become a priority issue and great challenge to clinicians. This requires appropriate sterilization and disinfection procedures and strict adherence to protocol in infection control policy. There is a need to evaluate the efficacy of newer disinfectants which have come into the market for better control of HAI. AIMS AND OBJECTIVES: The aim of this study was to evaluate and compare disinfection efficacy of three newer disinfectants– Novacide (didecyldimethylammonium chloride and polyhexamethylene biguanide, Silvicide a strong oxidizing agent (hydrogen peroxide and silver nitrate and Virkon, a powerful oxidizing agent (a stabilized blend of peroxygen compounds and potassium salts, pitting them against two time-honored conventional disinfectants phenol and lysol and testing them against common MDR clinical isolates, reference strains and spores. MATERIALS AND METHODS: All the disinfectants at different dilutions were tested for bactericidal efficacy by liquid suspension time-kill tests. A heavy initial microbial load was simulated by preparing bacterial inoculum. Numbers of viable cells were counted and reduction in microbial colony counts before and after disinfectant exposure was expressed as log reduction. RESULTS: Among the disinfectants, Novacide was most effective. All clinical MDR bacterial isolates and reference strains were killed within 30 seconds of exposure at 0.156% solution, whereas spores got killed after 30 minutes of exposure at 2.5% solution which is the recommended concentration. For Silvicide all vegetative bacteria were killed at 5% solution after 20 minutes contact time

  6. Recent developments and emerging therapies for type 2 diabetes mellitus.

    Science.gov (United States)

    Evans, A J; Krentz, A J

    1999-08-01

    Most patients with type 2 (non-insulin-dependent) diabetes mellitus require pharmacotherapy, initially as monotherapy and subsequently in combination, as adjuncts to diet and exercise. Exogenous insulin is ultimately required in a substantial proportion, reflecting the progressive natural history of the disease. Sulphonylureas and biguanides have been employed for over 4 decades as oral antidiabetic agents, but they have a limited capacity to provide long term glycaemic control and can cause serious adverse effects. Thus, more efficacious and tolerable antidiabetic agents are required. Recent years have witnessed the introduction of agents with novel modes of action, that is, the alpha-glucosidase inhibitors acarbose and miglitol (which reduce postprandial hyperglycaemia) and the first of the thiazolidinedione insulinsensitising drugs--troglitazone and rosiglitazone. Although the former has been withdrawn in some countries due to adverse effects, another 'glitazone' pioglitazone is expected to be approved in the near future. Other recently introduced drugs include glimepiride and the meglitinide insulin secretagogue, repaglinide. Attention is also focusing increasingly on combination therapy using insulin together with sulphonylureas, metformin or troglitazone. Rapid-acting insulin analogues are now being used as alternatives to conventional insulins; their role in the management of type 2 diabetes mellitus is presently uncertain but reports of a reduced frequency of hypoglycaemia are encouraging. The development of new drugs aims to counter the principal metabolic defects of the disorder, respectively, relative insulin deficiency and insulin resistance. Novel classes of rapid-acting secretagogues under evaluation include the morphilinoguanide BTS 67582 and the meglitinides mitiglinide (KAD 1229) and senaglinide (A-4166). Succinate ester derivatives represent a potential novel approach to improving beta-cell function through enhancement of insulin biosynthesis and

  7. Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer.

    Science.gov (United States)

    Menendez, Javier A; Joven, Jorge

    2014-01-01

    We are as old as our adult stem cells are; therefore, stem cell exhaustion is considered a hallmark of aging. Our tumors are as aggressive as the number of cancer stem cells (CSCs) they bear because CSCs can survive treatments with hormones, radiation, chemotherapy, and molecularly targeted drugs, thus increasing the difficulty of curing cancer. Not surprisingly, interest in stem cell research has never been greater among members of the public, politicians, and scientists. But how can we slow the rate at which our adult stem cells decline over our lifetime, reducing the regenerative potential of tissues, while efficiently eliminating the aberrant, life-threatening activity of "selfish", immortal, and migrating CSCs? Frustrated by the gene-centric limitations of conventional approaches to aging diseases, our group and other groups have begun to appreciate that bioenergetic metabolism, i.e., the production of fuel & building blocks for growth and division, and autophagy/mitophagy, i.e., the quality-control, self-cannibalistic system responsible for "cleaning house" and "recycling the trash", can govern the genetic and epigenetic networks that facilitate stem cell behaviors. Indeed, it is reasonable to suggest the existence of a "metabostem" infrastructure that operates as a shared hallmark of aging and cancer, thus making it physiologically plausible to maintain or even increase the functionality of adult stem cells while reducing the incidence of cancer and extending the lifespan. This "metabostemness" property could lead to the discovery of new drugs that reprogram cell metabotypes to increase the structural and functional integrity of adult stem cells and positively influence their lineage determination, while preventing the development and aberrant function of stem cells in cancer tissues. While it is obvious that the antifungal antibiotic rapamycin, the polyphenol resveratrol, and the biguanide metformin already belong to this new family of metabostemness

  8. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    Directory of Open Access Journals (Sweden)

    Karina Faccio Mello

    2011-02-01

    Full Text Available INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulated by phytohemagglutinin (PHA and oral hypoglycemic drugs. RESULTS: In both in vitro and ex vivo experiments, there was a reduction in cell proliferation after treatment with oral hypoglycemic drugs. When both drugs were used in combination, a high level of cytotoxicity was observed, which made analysis of immunomodulatory effects unfeasible. DISCUSSION AND CONCLUSION: We demonstrated that diabetes itself may reduce cell proliferation significantly when stimulated by PHA, which may indicate that diabetic patients have difficulties in promoting an efficient inflammatory response. Moreover, the use of oral hypoglycemic drugs may aggravate this situation.INTRODUÇÃO E OBJETIVOS: Tem sido sugerido que o diabetes mellitus tipo 2 (DM2 é uma manifestação da resposta inflamatória. As principais drogas utilizadas no tratamento do DM2 são as sulfonilureias e as biguanidas. O objetivo deste trabalho é demonstrar os efeitos moduladores na proliferação de linfócitos causada pelos hipoglicemiantes orais (clorpropamida e metformina, in vitro e ex vivo. MÉTODOS: Células mononucleares de sangue periférico foram isoladas de seres humanos por gradiente de centrifugação. Os linfócitos T foram estimulados com fito-hemaglutinina (PHA e hipoglicemiantes. RESULTADOS: Nos experimentos in vitro e ex vivo, mostramos a redução da proliferação celular quando do tratamento com drogas hipoglicemiantes orais. Quando as drogas foram utilizadas em combinação, foi

  9. Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

    Science.gov (United States)

    Donnelly, William T; Bartlett, Donald; Leiter, J C

    2016-07-01

    What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C

  10. Acidosis láctica por metformina desencadenada por una insuficiencia renal aguda Metformin-induced lactic acidosis due to acute renal failure

    Directory of Open Access Journals (Sweden)

    M.D. Macías-Robles

    2011-04-01

    Full Text Available La acidosis láctica es una complicación grave pero infrecuente asociada al empleo de metformina. Se discuten los mecanismos fisiopatológicos implicados en la acidosis láctica, con especial atención al papel potencial del fármaco. Presentamos un caso severo de este efecto secundario de la metformina en una paciente con diabetes tipo 2 que ingresó en el Servicio de Urgencias Hospitalario por un cuadro de insuficiencia renal aguda. El diagnóstico quedó apoyado por unos niveles séricos elevados de la biguanida, procedimiento escasamente utilizado en la práctica clínica. El tratamiento consiste en suspender la administración del fármaco e iniciar de forma inmediata la hemodiálisis con bicarbonato, lo cual proporciona un tratamiento sintomático y etiológico al eliminar del suero tanto el lactato como el antidiabético oral. Los síntomas de la acidosis láctica por metformina son inespecíficos y el comienzo es sutil, lo que hace necesario un alto nivel de sospecha para establecer un diagnostico precoz.Lactic acidosis is a serious but uncommon side effect of metformin use. We discuss the pathophysiological mechanisms of lactic acidosis with particular regard to the role played by the drug as a potential cause of the entity. We report on a severe case of this kind of drug toxicity in a patient with type 2 diabetes mellitus, admitted to the emergency department with acute renal failure symptoms. The diagnosis was supported by elevated serum levels of the biguanide, a procedure scarcely used in clinical practice. The management of this complication consists in drug discontinuation and hemodialysis with bicarbonate that provides symptomatic and ethiological treatment by removing both the lactate and the hypoglycemic agent from the serum. Since the symptoms of metformin-associated lactic acidosis are unspecific and its onset is subtle, a high level of suspicion is needed to establish an early diagnosis.

  11. Effects of A Low-Carbohydrate Diet and A Low-Fat Diet on Weight and Glycemic Control in Type 2 Diabetics Mellitus%低碳水化合物饮食和低脂肪饮食对2型糖尿病患者体质量及血糖的影响

    Institute of Scientific and Technical Information of China (English)

    曹爱华; 孙丽珍; 崔静稳; 张宪静

    2011-01-01

    目的 比较低碳水化合物饮食和低脂肪饮食1年对2型糖尿病(T2DM)患者体质量及血糖的影响.方法 采用随机对照的方法,将90例超重T2DM患者随机分为低碳水化合物饮食+双胍类药物治疗组(A组)和低脂肪饮食+双胍类药物治疗组(B组),各45例.A组患者给予低碳水化合物饮食+双胍类药物治疗;B组患者给予低脂肪饮食+双胍类药物治疗.分别在治疗前及治疗3、6、12个月检测两组患者的体质量、糖化血红蛋白(HbA1c)、血压和血脂.结果 两组患者治疗前后体质量及高密度脂蛋白(HDL)水平变化比较,差异有统计学意义(P<0.01);而两组患者血压及血清总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TG)、HbA1c水平变化比较,差异无统计学意义(P>0.05).两组患者体质量明显下降及HbA1c的减少主要发生在治疗的前3个月,A组、B组体质量平均下降1.8 kg/月和1.0 kg/月,HbA1c均下降0.6%;但在1年里两组患者体质量减轻均为3.4 kg.结论 对于超重的T2DM患者,1年的低碳水化合物饮食及低脂肪饮食对HbA1c的影响类似,血压未受影响;但低碳水化合物饮食者体质量下降较低脂肪饮食者快,且较后者能显著提高HDL水平.%Objective To compare the effects of a 1 - year intervention with a low - carbohydrate and a low - fat diet on weight and glycemic control in patients with type 2 diabetes mellitus. Methods The randomized controlled clinical trial was taken to assign 90 0verweight patients with type 2 diabetes mellitus to the low - carbohydrate diet ( A ) group and low - fat diet ( B ) group, with 45 patients in each. The patients in the group A were given a low - carbohydrate diet and biguanides; while those in the group B were given a low - fat diet and biguanides. The body weight, glycosylated hemoglobin ( HbA1c ), blood pressure and lipids were detected before treatment and 3 , 6. and 12 months after the treatment. Results Before and after the

  12. 连续性血液净化救治对比剂急性肾损伤的临床研究%The Clinical Research of Contrast Agent-induced Acute Renal Injury with Treatment of Continuous Blood Purification

    Institute of Scientific and Technical Information of China (English)

    孟建中; 荣鹏; 周春华; 王素霞; 刘文渊; 景颖; 贾凤玉; 葛彦明; 岳冀

    2011-01-01

    To study the clinical features of Contrast agent - induced acute renal injury(CI - AKI) with treatment of continuous blood purification (CBP). 32 cases of CI - AKI patients we treated from May 2003 to May 2010 were selected. We analyzed the patho-genesis, detected the continuous changes of the levels of serum creatinine ( Scr) , uric acid (UA) , high - sensitivity C - reactive pro-tein (hs - CRP) and other biochemical indicators before and after imaging and before and after CBP treatment, observed the mortality of CI - AKI patients in 28 days. The law of the incidence; 17 cases with coronary heart disease with diabetes suffered from CI - AKI af-ter receiving treatment in the cardiac catheterization. Among them, 13 cases (40.62% ) while taking biguanide hypoglycemic agents. Clinical features; At 24h after angiography, uric acid and hs - CRP levels were significantly increased, and peaked at 48h. The Scr level increased at 48h after angiography, and reached a peak at 72h after surgery. The correlation analysis showed that serum uric acid levels and changes in hs - CRP levels showed a positive correlation (r = 0.66,P<0.05). Outcome: 29 cases (90.62% ) patients out of oliguria after 48h in CBP treatment, people/kidney were to survive. 2 cases (6.25% ) due to renal failure, survival was dependent on maintenance dialysis. 1 patient died (3.12% ) of malignant arrhythmia after PCI, 12 d. Biguanide hypoglycemic is an independent risk factor in diabetic patients suffering from CI - AKI after PCI. The changes of Serum uric acid and hs - CRP levels are sensitive indicator reflect cell damage in CI - AKI. CBP can improve renal perfusion, accelerate the excretion of uric acid and contrast agent, re-duce the effect of oxidative stress in the renal tubular epithelial cells, protect renal function.%研究连续性血液净化(CBP)救治对比剂急性肾损伤(CI-AKI)的临床特点.选取2003年5月至2010年5月间救治的32例CI-AKI患者,分析发病规律,检测造影前、

  13. 外用中药通水散辅助治疗肥胖型高血压疗效观察%Clinical analysis of treatment for obesity hypertension with western medicine and Chinese medicine Tong Shui San

    Institute of Scientific and Technical Information of China (English)

    陈专心

    2015-01-01

    Objective To analyze clinical effect of treatment for obesity hypertension with western medicine and Zhong Yao Wai Yong Tong Shui San,to provide a reference for clinical drugs.Methods 150 obesity hyperten-sion patients were selected,they were divided into group A,B,C according to mathematical random method,50 cases in each group.Ammonia amlodipine was used in group A,dimethyl biguanide was used in group B,besides ammonia amlodipine and dimethyl biguanide,self-made Zhong Yao Wai Yong Tong Shui San were used in group C.Index such as insulin and blood pressure were compared in three groups.Results Rate of blood pressure control of group C was 96.00%,higher than that of group A (80.00%)and group B (82.00%),there were statistical difference (χ2 =6.495,P=0.008;χ2 =6.215,P=0.010);after the treatment,DBP and SBP of group C were (73.75 ±6.83)mmHg and (122.66 ±11.46)mmHg,better than group A and group B(all Pgroup B >group A,there were statistical difference (all P <0.05 ).Conclusion Combination of western medicine and Zhong Yao Wai Yong Tong Shui San has a good performance in improving blood pressure,blood lipids and insulin.%目的:探讨外用中药通水散辅助治疗肥胖型高血压患者临床效果,为临床用药提供参考。方法选择肥胖型高血压患者150例,按照数字表法分为A、B、C三组,各50例,A组单用氨氯地平治疗,B组联合氨氯地平及二甲双胍治疗,C组在B组基础上使用自制中药通水散外用治疗,对比三组治疗后胰岛素、血压等指标。结果 C组降压有效率96.00%,明显高于A组(80.00%)及B组(82.00%),差异均有统计学意义(χ2=6.495,P=0.008;χ2=6.215,P=0.010);C组治疗后DBP(73.75±6.83)mmHg,改善均优于A组及B组(t=5.395,P=0.015;t=5.529,P=0.013),SBP为(122.66±11.46)mmHg,改善均优于A组及B组(t=4.765,P=0.021;t=4.664,P=0.024);B组及C组TC

  14. Analysis of hypoglycemic drugs of patients with type 2 diabetes in Qingxin Distric in Qingyuan city%清远市清新区2型糖尿病患者降糖药物的用药分析

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    罗金娥; 余德生; 姜学辉

    2016-01-01

    Objective:To provide reference for clinical rational drug use in the local, we investigate hypoglycemic drugs used in type 2 diabetic patients in Qingxin Distric in Qingyuan city in Guangdong Province. Methods:2380 cases of patients with type 2 diabetes in Qingxin Distric in Qingyuan city in Guangdong Province as the research object, questionnaire survey, and analyzed the use of antidiabetic drugs. Results:A higher proportion of drug use is: biguanides, using the rate of 89.97%. Secondly, a sulfonylurea, alpha glucosidase inhibitor, use rates were 71.97% and 55.97%. High frequency of use of drugs, metformin, acarbose, frequency of use are:79.03%, 57.02%. Double guanidine kind+sulfonylurea combination rate:71.47%, is the proportion of previous use of drug combination in the largest category. Followed by : biguanides + sulfonylurea + alpha glucosidase inhibitor drugs combination accounted for 50.63%. Fasting blood glucose (FBG) and lower levels of 2hPBG, were of relatively short duration, hypoglycemic drug varieties less. While the FBG and 2hPBG levels were higher in the patients, the disease is relatively longer, taking more hypoglycemic drugs. A short course of patients, complications and hypoglycemic drug relatively few species. While patients with longer disease duration, complications and use of hypoglycemic drugs more varieties. Conclusion:Hypoglycemic medication is more scientific and reasonable, accord with the clinical treatment of specification, type 2 diabetic patients in Qingxin Distric in Qingyuan city in Guangdong Province. Part of the control blood sugar of patients is not ideal by hypoglycemic drugs, can be used insulin treatment.%目的:调查分析广东省清远市清新区2型糖尿病患者的降糖药物使用情况,为临床合理用药提供参考。方法:选择广东省清远市清新区2380例2型糖尿病患者作为研究对象,发放调查问卷进行调查,并对降糖药物使用情况进行总结分析。结果:药物使

  15. 新诊断中老年2型糖尿病患者的初始治疗策略与血糖控制%Initial treatment strategies and blood glucose control for newly diagnosed type 2 diabetes mellitus in the middle-aged and elderly

    Institute of Scientific and Technical Information of China (English)

    孙明晓; 王晓霞; 鲜彤章; 蒋蕾; 汪耀; 迟家敏; 郭立新; 于冬妮; 李铭; 李慧; 潘琦

    2011-01-01

    medication), group B (single oral hypoglycemic agent), group C (combined oral hypoglycemic agents), group D (treatment including insulin). Results Although receiving the different treatments, the 771 patients had a similar mean glycated hemoglobin level, from 7.2% to 7.7%, among the four kinds of intervention before entering the study. The increased intensity and complexity after therapy adjustment along with the increased glycated hemoglobin level was observed at baseline. The corresponding relationships between medication and HbA1c were as follow: without medication-6.1%, single oral hypoglycemic agent-7.2%, combined oral hypoglycemic agents-7.7%, treatment including insulin-9.2%. After 20 months of follow-up, the mean fasting glucose and glycated hemoglobin were 6.6 mmol/L and 6.2%, separately. According to the target glycated hemoglobin level of less than 7.0%, all four-kinds of therapies had high achievement rates, which were all above 80% except that was 63.2% in group D. Sulphonylurea and biguanide as initial single oral hypoglycemic agent therapy had the similar effectiveness on glucose control and target glycated hemoglobin achievement. Conclusions According to the levels of glucose and glycated hemoglobin, multiple individual therapies should be enacted at the beginning of treatment. The strategy mainly based on sulphanylurea and biguanide is proved to be persistently effective in newly-diagnosed middle-aged and elderly diabetic patients in China.

  16. Avaliação de um novo produto na desinfecção do tonômetro de aplanação de Goldmann The evaluation of a new product in the desinfection of the applanation tonometer

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    Nelson Maimone

    2001-11-01

    Full Text Available Objetivo: Avaliar a eficácia de um produto usado habitualmente para limpeza de lentes de contato (CompleteÒ: poliexametileno de biguanida (TrisChemTM, tiloxapol, trometamina e EDTA em solução isotônica estéril na desinfecção do cone do tonômetro de aplanação. Métodos: O cone permaneceu imerso na solução no período médio de 28 minutos. Foi utilizado um recipiente para limpeza de lentes de contato e um suporte de isopor. Ao final de cada dia, durante 22 dias, foram realizadas culturas para fungos e bactérias, exames diretos para fungos e bacterioscopia por Gram. Foi testado "in vitro" o poder bactericida e fungicida do produto para S. aureus ATCC#25923, E. coli ATCC#25922, P. aeruginosa ATCC#27853, C. albicans ATCC# 76615, A. niger ATCC#16404. Resultados: Nas culturas, nos exames diretos para fungos e nas bacterioscopias por Gram não foram identificados microrganismos. No estudo "in vitro", foram necessárias 48 horas para eliminação completa de todas cepas estudadas. Conclusão: Não foram encontradas bactérias e fungos em todos exames realizados da solução e recipiente. No entanto, os testes "in vitro" demonstraram que o tempo de imersão do cone na solução (média de 28 minutos é insuficiente para eliminação completa dos microrganismos, o que inviabiliza o uso desse produto na desinfecção do cone plástico do tonômetro de aplanação.Purpose: To evaluate the efficacy of a product which is normally used for cleaning of contact lenses (CompleteÒ: polyhexamethylene biguanide (Tris ChemTM, Tyloxapol, USP, Tromethamine, USP, and Edetate disodium, USP, in sterile isotonic solution in the disinfection of the cone of the applanation tonometer. Methods: The cone remained immersed in the solution for an average period of 28 minutes. A container for cleaning the contact lenses and a polystyrene support were used. At the end of each day, for 22 days, cultures for fungi and bacteria were carried out as well as direct

  17. Efficacy of Pioglitazone in Treatment of Steatohepatitis with Diabetes Mellitus%吡格列酮对糖尿病合并非酒精性脂肪肝炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    徐园园; 纪易斐

    2011-01-01

    Objective To observe the efficacy and adverse drug reactions of pioglitazone in treatment of non-alcoholic steatohepatitis (NASH) with type 2 diabetes mellitus. Methods Fifty five patients with NASH were randomly divided into two groups: pioglitazone group with pioglitazone 30 mg per day, while control group with Hypoglycemic drug except for thiazolidine dione and Biguanides, the period of treatment was 24 weeks. Fasting blood glucose,2-hour postprandial blood glucose, fasting blood insulin,glycosylated hemoglobin,insulin resistance index,alanine aminotransferase,aspartate aminotransferase blood lipid and the degree of fatty liver were measured before and after the treatment. Results Both the two groups significantly reduced fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin after treatment,but there were not significant differences in two groups( P > 0.05 ). Compared with the patients in control group, Pioglitazone group had significant differences in lower fasting blood insulin and insulin resistance index,improvement liver function and blood lipid,modification the degree of fatty liver( P <0.05 ). Conclusion Pioglitazone can increase insulin sensitivity, improve the abnormalities of enzyme tests, reduce insulin resistante and improve the fatty liver.%目的 临床观察胰岛素增敏剂吡格列酮对2型糖尿病合并非酒精性脂肪肝炎患者治疗的有效性和安全性.方法 将55例2型糖尿病合并非酒精性脂肪肝炎患者随机分为两组,吡格列酮组给予吡格列酮30 mg,1次/d,对照组给予除噻唑烷二酮类以外的其他降糖药物治疗,疗程均为24周.比较两组治疗前后指标:空腹血糖、餐后2 h血糖、空腹胰岛素、糖化血红蛋白、胰岛素抵抗指数、天冬氨酸转氨酶、丙氨酸转氨酶、血脂及脂肪肝程度.结果 治疗后两组空腹血糖、餐后2 h血糖、糖化血红蛋白均有明显改善,两组比较差异无统计学意义(P>0.05),吡格

  18. 羊毛织物抗菌防缩功能整理%An Antimicrobial and Shrink-Resistance Treatment of Wool Textiles

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    俞鑫; 龙海如; 高远

    2013-01-01

    应用常用杀菌剂六亚甲基双胍(PHMB)处理由过一硫酸氢钾复合盐和亚硫酸钠预处理的羊毛织物,研究整理后羊毛织物的防缩和抗菌性能.在浸轧和浸渍两种处理工艺中,预处理过的羊毛织物对PHMB的结合率(owf,相对织物质量百分比)分别高达4.6%和4.4%.这种抗菌处理使得羊毛织物具有高效的抗茵性能,几乎能够杀灭所有接种大肠杆菌.该抗菌能力也有耐洗性,经过相当于40~50次ISO 5A重复洗涤后,PHMB处理过的羊毛织物对大肠杆菌的灭菌率仍高达93.3%(浸轧)和99.3%(浸渍).在扫描电镜下观察,发现PHMB能覆盖羊毛表面的磷片,从而产生防缩效果.PHMB含量(owf)为8%处理后的羊毛织物,经过相当于40~50次ISO 5A重复洗涤,其面积毡缩率降低至8.4%(浸轧)和6.1%(浸渍).因此,PHMB的一步法处理使得羊毛织物同时具有了抗茵和防缩的双重性能.%The common biocide polyhexamethylene biguanide (PHMB) was applied to wool fabrics which had been pretreated with potassium peroxymonosulf ate ( PMS) and sodium sulf ite (Na2 SO3), and the antibacterial and shrink resistant properties of the fabrics were studied. In padding and exhaustion processes, the pretreated wool fabrics could take up 4. 6% and 4. 4% (on the weight of fabric, owf) of PHMB, respectively. This treatment conferred effective antibacterial activity to the fabrics which killed almost all inoculated bacteria. The antibacterial activity was durable to washing. PHMB treated fabrics resulted in 93. 3% (by padding) and 99. 3% (by exhaustion) bacterial reduction against Escherichia coli after 40 - 50 ISO 5A washing cycles. Under scanning electron microscopy, PHMB was observed to cover the cuticles on the wool fibres and therefore enhanced shrink resistance of the fabrics. The area shrinkage of wool fabrics treated with 8% (owf) PHMB was further reduced to 8. 4% (by padding) and 6.1% (by exhaustion) after 40 - 50 ISO 5A washes. Thus, a

  19. 上海市金山区2型糖尿病患者血糖控制及用药现状调查%Survey on status of glycemic control and antidiabetic drugs therapy in patients with type 2 diabetes mellitus in Jinshan District of Shanghai

    Institute of Scientific and Technical Information of China (English)

    吕家爱; 李轶群; 高霞

    2013-01-01

    OBJECTIVE To evaluate the glycemic control in patients with type 2 diabetes mellitus in Jinshan District Community of Shanghai and describe the medication status.METHODS 110 patients with type 2 diabetes mellitus in the community were collected by random sampling method and managed with community diabetes management software.Questionnaire surveys and physical examinations were conducted on these patients.RESULTS The mean HbAlc concentration was (7.3 ±1.3) % of 110 patients with type 2 diabetes.According to the recommended targets of Chinese Diabetes Society (CDS),28.2% of the participants achieved the goal of HbA1c level (< 6.5%) while 4.5% of the participants achieved all three target goals of HbA1c level (< 6.5%),blood pressure (< 130/80 mm Hg) and triglyceride level (< 1.5 mmol/L).The ordinal ratios of antidiabetic drug consumption were Sulfonylureas (63.5%),Biguanides (50%) and Insulin (15.4%).The ratio of using single antidiabetic drug in glycemic control group was higher than that in poor glycemic control group.CONCLUSION As considerable proportion of patients with type 2 diabetes mellitus can not achieve the goal of HbAlc level with a low ratio of using insulin therapy.Therefore,it is a urgent need to improve prevention and control of diabetes mellitus.%目的 评价金山区社区管理的2型糖尿病患者的血糖控制情况,描述2型糖尿病患者的用药现状.方法 采用单纯随机抽样的方法抽取本区2型糖尿病患者110人进行问卷调查和体检.结果 110位患者,糖化血红蛋白(HbA1c)平均值为(7.3±1.3)%.根据2007年中华医学会糖尿病学分会(CDS)推荐的控制目标,28.2%的患者HbA1c达标(<6.5%),4.5%的患者HbA1c、血压(BP)和甘油三酯(TG)都达标(HbA1c< 6.5%,BP< 130/80 mm Hg,TG< 1.5 mmol/L);降糖药使用位居前3位的依次为磺脲类、双胍类、胰岛素,分别占使用降糖药总人数的63.5%、50.0%和15.4%;血糖控制组患者单用

  20. 糖尿病社区护理对患者生活质量的影响%Influence of community nursing on quality of life in patients with diabetes

    Institute of Scientific and Technical Information of China (English)

    陈丽青

    2014-01-01

    目的:观察社区护理对糖尿病患者生活质量的影响。方法:2012年11月-2013年11月收治糖尿病患者100例,作为研究对象,随机分为试验组和对照组。对照组均采用常规的药物治疗,如胰岛素、磺酰脲类、双胍类、噻唑烷酮类等;试验组在此基础上还配合饮食、运动、用药、健康教育等社区护理。比较两组患者在治疗3个月后的遵医行为、健康理念和血糖控制等方面的差异。结果:两组患者经治疗后,血糖浓度都得到了有效的控制,但是试验组中92%患者有健康理念和对照组的32%比较,差异具有统计学意义(P<0.05)。结论:有效的社区护理能促进患者的遵医行为和健康行为,使血糖浓度更好地得到控制,对提高患者的生活质量有积极的作用,并能减少并发症的发生。%Objective:To observe the influence of community nursing on quality of life in patients with diabetes.Methods:100 cases of patients with diabetes were admitted from November 2012 to November 2013.They were as the object of study and randomly divided into experimental group and control group.Two groups were treated with conventional drug therapy,such as insulin,sulfonylurea,biguanides,thiazolidinedione.The experimental group on this basis were given community nursing such as the diet,activity,drug use,health education.Compare the difference of treatment compliance,health concept and blood sugar control of two groups after 3 months of treatment.Results:The blood sugar concentration of two groups had been effectively controlled after treatment,but 92% patients had health concept in the experimental group,and the control group was 32% .The difference was statistically significant(P<0.05).Conclusion:Effective community nursing can improve the treatment compliance and healthy behavior.Better controlling of the blood glucose has a positive effect on improving the quality of life of patients,and it can reduce the

  1. Clinical Analysis of 23 Cases of Diabetic Lactic Acidosis%糖尿病乳酸性酸中毒23例临床分析

    Institute of Scientific and Technical Information of China (English)

    尹延伟; 张中东; 胡爱民

    2012-01-01

    目的:探讨糖尿病乳酸性酸中毒的诱发因素、临床特点,提高对糖尿病乳酸性酸中毒的诊断及治疗水平.方法:对确诊为糖尿病乳酸性酸中毒的23例患者临床诊治资料进行回顾性总结和分析.结果:本组23例糖尿病乳酸性酸中毒患者平时口服双胍类降糖药控制血糖者有20例(87.0%);有明确感染病史的患者19例(82.6%);肾功能不全患者11例(47.8%);心功能不全患者8例(34.8%)及肝功能异常患者5例(21.7%).经积极治疗,23例糖尿病乳酸性酸中毒患者抢救成功18例,死亡5例.结论:糖尿病患者在使用双胍类降糖药,并发感染,器官功能异常等其他情况时能够增加其发生乳酸性酸中毒的风险.糖尿病乳酸性酸中毒发病急,病情严重,死亡率高,其临床表现常被原发疾病的症状、体征所掩盖,临床工作中容易误诊与漏诊,应加以重视.%Objective: To investigate the inducement and clinical features of diabetic lactic acidosis. To improve the diagnosis and treatment of patients with diabetic lactic acidosis. Method:The clinical data of 23 cases for diabetic lactic acidosis were analysed retrospectively. Result:In 23 cases ,20 cases with biguanidestreatment ( 87. 0% ) ;19 cases with a clear history of infection ( 82. 6% ) ; 11 cases with chronic renal insufficiency (47. 8% ) ;8 cases with heart failure(34. 8% ) ; 5 cases with abnormal liver function(21. 7% ). After active treatment, 18 cases with successful rescue, and 5 cases with death. Conclusion: Using biguanides treatment, infection and organ dysfunction can increase the risk of diabetic lactic acidosis for diabetic patients. Diabetic lactic acidosis is an acute disease and has such characteristics as seriously condition and high case mortality rate. Clinical manifestations of diabetic lactic acidosis were usually covered by signs and symptoms of primary diseases, causing missed diagnosis and misdiagnosis frequently. So we should attach importance to this

  2. INVESTIGATION ON PRODUCTION AND MANAGEMENT STATUS OF SKIN AND MUCOUS MEMBRANE ANTIBACTERIAL PREPARATIONS IN SHANGHAI%上海市皮肤黏膜抗(抑)菌产品生产与管理现状调查

    Institute of Scientific and Technical Information of China (English)

    孙玉卿; 毛洁; 周晓鹂

    2011-01-01

    Objective To know the production and management status of skin and mucous membrane antibacterial preparations in Shanghai, and to explore inspection and management methods to solve relevant problems. Methods Field sampling investigation was used to know the quality and manufactories management status of all the skin and mucous membrane antibacterial preparations in Shanghai. Results There are 17 types of skin and mucous membrane antibacterial preparations in Shanghai. The germicidal ingredient are mainly triclosan, biguanide and its compound preparations. The antibacterial ingredient contents of are qualified to national guidelines, and all the products have antibacterial effects on Escherichia coli and Staphylococcus aureus according to test results of certificated laboratory. Hygienic safety evaluation were made on 16 of the products, and 7 of the evaluation reports are qualified according to Hygienic Safety Evaluation Regulations on Disinfection Products of Ministry of Health. Conclusion All the skin and mucous membrane antibacterial preparations in Shanghai were manufactured under permission, and their antibacterial ingredient contents and antibacterial effects were qualified. However, there were defects concerning hygienic safety evaluation, and inspection should be strengthened accordingly.%目的 了解上海市皮肤黏膜抗(抑)菌产品的生产与管理现状,发现存在问题,探讨监管方法.方法 用现场抽样调查的方法,对本市所辖皮肤黏膜抗抑菌产品质量和生产企业管理情况进行了调查.结果 本市企业生产的皮肤黏膜抗(抑)菌产品共17种,这些产品的主要杀菌成分以三氯羟基二笨醚和双胍类化合物及其复方制剂为主,产品抗菌成分的含量值符合国家限量值规定.经过上海市认证实验室检测,17种产品对大肠杆菌和金黄色葡萄球菌均具有抗(抑)菌效果.17种产品中,有16种产品完成卫生安全评价,其中有7件产品的评价报告内容

  3. An effective analysis of treating 84 cases of diabetes II with Qiwei Baizhu San%七味白术散加减辅助治疗84例2型糖尿病的疗效分析

    Institute of Scientific and Technical Information of China (English)

    牛延峰

    2014-01-01

    Objective: To analyze clinical efficacy and safety of Qiwei Baizhu San on diabetes II. Methods: 167 patients with diabetes II were randomly divided into the control group and the observation group. The control group was given sulfonylureas, biguanides, or plus insulin; another was given Qiwei Baizhu San more. FPG in 60d, PBG, glycated hemoglobin index and safety of drugs were compared. Results:The two groups could decrease biochemical indexes after treatment, but the observation group was better (P<0.05);the total efficacy in the observation was 96.43%, obviously higher than 87.95%in the control (P<0.05); the rate of adverse reactions in the observation was 2.38%, obviously lower than 10.84%in the control (P<0.05). Conclusion:Qiwei Baizhu San showed good clinical efficacy, could reduce blood sugar through multi-paths and multi-targets, protect pancreatic function, with less adverse reactions, and was worthy of promotion.%目的:分析2型糖尿病采用七味白术散加减辅助治疗的临床疗效和安全性。方法:采用随机数字表法将167例2型糖尿病患者分为两组,对照组予磺脲类、双胍类等降糖药或者联合胰岛素治疗,观察组在对照组基础上予七味白术散加减治疗,对比60d后空腹血糖、餐后血糖、糖化血红蛋白指标和药物安全性。结果:两组均能够降低治疗后生化指标,但观察组降低治疗后生化指标幅度明显高于对照组,P<0.05;观察组总有效率为96.43%,明显高于对照组87.95%,P<0.05;观察组不良反应发生率为2.38%,明显低于对照组10.84%,P<0.05。结论:七味白术散辅助治疗2型糖尿病疗效确切,能够通过多途径、多靶点发挥降血糖作用,而且可保护胰腺功能,不良反应少,建议临床继续探讨和推广。

  4. A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease

    Directory of Open Access Journals (Sweden)

    Fisman Enrique Z

    2009-07-01

    Full Text Available Abstract Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1, the dipeptidyl peptidase 4 (DPP-4 inhibitors, dual peroxisome proliferator-activated receptors (PPAR agonists (glitazars and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD. Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM

  5. Antihyperglycemic, antihyperlipidemic, anti-inflammatory and adenosine deaminase–lowering effects of garlic in patients with type 2 diabetes mellitus with obesity

    Directory of Open Access Journals (Sweden)

    Kumar R

    2013-01-01

    Full Text Available Rahat Kumar,1 Simran Chhatwal,1 Sahiba Arora,2 Sita Sharma,3 Jaswinder Singh,1 Narinder Singh,1 Vikram Bhandari,1 Ashok Khurana41Department of Pharmacology, 2Department of Biochemistry, 3Department of Obstetrics and Gynecology, 4Department of Medicine, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, IndiaIntroduction: Type 2 diabetes mellitus is a chronic disorder characterized by chronic hyperglycemia, with long term macrovascular and microvascular complications. The treatment is lifestyle management, exercise, weight control, and antihyperglycemic drugs such as sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, and meglitinide. Recently, a direct association between high levels of C-reactive protein and serum adenosine deaminase levels in patients with uncontrolled diabetes with long-term complications has been seen. This study was conducted to assess the antihyperglycemic, lipid-lowering, anti-inflammatory, and improving glycemic control of garlic in type 2 diabetes patients with obesity.Materials and methods: This was an open-label, prospective, comparative study, conducted on 60 patients having type 2 diabetes mellitus and obesity. The patients were divided into two groups of 30 each, of either sex. Group 1 was given metformin tablets, 500 mg twice a day (BD/three times a day (TDS, after meals, and group 2 was given metformin tablets, 500 mg BD/TDS, after meals, along with garlic (Allium sativum capsules, 250 mg BD. Patients were routinely investigated for fasting and postprandial blood glucose, glycosylated hemoglobin (HbA1c, serum adenosine deaminase levels and lipid profile (serum cholesterol, high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein cholesterol at the start of the study. Patients were followed up for 12 weeks, with monitoring of fasting and postprandial blood glucose at 2 week intervals, and monitoring of the other parameters at the end of study

  6. Analysis of Application of Oral Hypoglycemic Drugs in Outpatient Department of the Central Hospital of Nanchong during 2012-2014%2012—2014年南充市中心医院门诊口服降糖药应用分析

    Institute of Scientific and Technical Information of China (English)

    徐秀华; 冯婧; 王龙飞

    2015-01-01

    目的:分析南充市中心医院(以下简称"我院")2012—2014年门诊口服降糖药的应用情况和发展趋势,为糖尿病药物治疗提供参考.方法:回顾性统计分析我院2012—2014年门诊降糖药的销售数量、销售总金额、用药频度( defined daily dose system,DDDs)、限定日费用( daily drug cost,DDC),并根据各药的DDDs排序和销售金额排序,算出排序比.结果:我院门诊口服降糖药销售金额整体呈上升趋势,磺酰脲类、双胍类、α-葡萄糖苷酶抑制剂的销售金额增幅大;二甲双胍使用频率高,连续3年居第1位;二甲双胍日平均费用较低,排序比连续3年大于1.结论:我院2012—2014年门诊口服降糖药临床使用基本合理,二甲双胍使用频率高,符合安全、有效、经济的用药原则.%OBJECTIVE:To analyze the status quo and development tendency of oral hypoglycemic drugs for outpatients in the Central Hospital of Nanchong( hereinafter referred to as "our hospital") during 2012-2014,and to provide reference for the medication of diabetes.METHODS: Retrospective analysis was conducted in terms of the consumption amount,consumption sum,defined daily dose system ( DDDs ),and daily drug cost ( DDC ); and the ranking ratio was calculated based on the ranking of DDDs and medication cost of oral hypoglycemic drugs.RESULTS:The consumption sum of oral hypoglycemic drugs for outpatients in our hospital showed an increase tendency in general,especially for sulfonylurea,biguanides and alpha glucosidase inhibitors.The use frequency of metformin continuously dominated the first place during the three years,which had a low cost per day,and the ranking ratio was over 1 during the three years.CONCLUSIONS: The application of oral hypoglycemic drugs for inpatients in our hospital is basically rational during 2012-2014,and metformin has a high frequency of usage,which is conform to the principle of safe,effective and economic medication.

  7. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

    Science.gov (United States)

    Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cuyàs, Elisabet; Corominas-Faja, Bruna; Rodríguez-Gallego, Esther; Fernández-Arroyo, Salvador; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

    2014-01-01

    Therapeutic interventions based on metabolic inhibitor-based therapies are expected to be less prone to acquired resistance. However, there has not been any study assessing the possibility that the targeting of the tumor cell metabolism may result in unforeseeable resistance. We recently established a pre-clinical model of estrogen-dependent MCF-7 breast cancer cells that were chronically adapted to grow (> 10 months) in the presence of graded, millimolar concentrations of the anti-diabetic biguanide metformin, an AMPK agonist/mTOR inhibitor that has been evaluated in multiple in vitro and in vivo cancer studies and is now being tested in clinical trials. To assess what impact the phenomenon of resistance might have on the metformin-like “dirty” drugs that are able to simultaneously hit several metabolic pathways, we employed the ingenuity pathway analysis (IPA) software to functionally interpret the data from Agilent whole-human genome arrays in the context of biological processes, networks, and pathways. Our findings establish, for the first time, that a “global” targeting of metabolic reprogramming using metformin certainly imposes a great selective pressure for the emergence of new breast cancer cellular states. Intriguingly, acquired resistance to metformin appears to trigger a transcriptome reprogramming toward a metastatic stem-like profile, as many genes encoding the components of the degradome (KLK11, CTSF, FREM1, BACE-2, CASP, TMPRSS4, MMP16, HTRA1), cancer cell migration and invasion factors (TP63, WISP2, GAS3, DKK1, BCAR3, PABPC1, MUC1, SPARCL1, SEMA3B, SEMA6A), stem cell markers (DCLK1, FAK), and key pro-metastatic lipases (MAGL and Cpla2) were included in the signature. Because this convergent activation of pathways underlying tumor microenvironment interactions occurred in low-proliferative cancer cells exhibiting a notable downregulation of the G2/M DNA damage checkpoint regulators that maintain genome stability (CCNB1, CCNB2, CDC20, CDC25C

  8. 2型糖尿病患者血糖控制早期个体化治疗策略与达标研究%The relationship of early individual glycemic control strategy and reaching standard in newly diagnosed type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    孙明晓; 蒋蕾; 于冬妮; 汪耀; 迟家敏; 郭立新; 李铭; 李慧; 鲜彤章

    2013-01-01

    Objective To analyze the early therapy strategy on glucose control in type 2 diabetic patients.Methods From June 2002 to May 2003,the medication and blood glucose control in 1396 cases with type 2 diabetes in national 10 grade 3A hospitals were retrospectively analyzed.The patients were diagnosed newly or within one year in CDCPS (Chinese Diabetes Complication Prevention Study),with (51 ± 9) yrs,body mass index (BMI) (24.9 ± 3.0) kg/m2.Besides the same instruction of lifestyle intervention,the patients were further divided as four groups:without intervention (group A),single oral hypoglycemic agent (group B),combined oral hypoglycemic agents (group C) and treatment including insulin(group D).The X2 test and analysis of covariance was used for count data and measurement data between groups.The paired t test was used comparison before and after the intervention.Pearson correlation analysis was used for factors affecting the efficacy of glucose analysis.Results (1) The level of HbA1 c at baseline was (7.3-± 1.9)%,and the fasting blood-glucose(FBG) was (7.5 ± 2.4)mmol/L among the four intervention group betore the treatment adjusted.After 20 months of follow-up,the mean FBG and HbAlc reached to (6.7-± 1.6) mmol/L and (6.1 ± 1.4) %,respectively.(2) For patients with HbAle > 7%,sulfonylurea and (or) biguanide monotherapy or combination therapy in this study was the most frequently chosen treatment.Compliance rates of HbAlc were 79.2%,81.9%,respectively.The difference was not statistically significant.(3) HbA1 c levels at the end of the follow-up and the patient's age (r =0.087,P <0.01),initial HbAlc levels (r =0.228,P < 0.001) showed a significant positive correlation.But HbA1 clevels showed no correlation with body weight,BMI and hypertension(r =0.053,0.011,0.019,-0.034,all P > 0.05).Conclusion According to the levels of glucose and HbA1 c,the early individualized therapy strategy mainly based on sulphanylureas and/or biguanides is proved to be

  9. This Issue at A Glance

    Directory of Open Access Journals (Sweden)

    Hormoz Chams

    2014-05-01

    Full Text Available In the retrospective investigation titled “Risk factors evaluation of threshold retinopathy of prematurity” at a tertiary ophthalmic center in Tehran, Iran, the authors have studied 859 premature neonates during one year (2008-2009. 791 eyes have had retinopathy of prematurity (ROP and 7.4% of them presented threshold retinopathy (TROP. The investigators aim has been to present and compare the risk factors of ROP and TROP and also to emphasize that the proposed criteria1 for investigation of ROP and TROP are not very precise and valuable for the developing countries. For example they remark that 33% of their TROP had birth weight of more than 1,500 grams. In this investigation the most important risk factors for TROP have been delay in initial examination, low weight, low gestation age, and duration of oxygen therapy. In another presentation, the authors have investigated “The prevalence of viral conjunctivitis in patients who referred to eye specialist hospitals in Tehran, Iran”. They received 150 swap samples and after DNA extraction, and multiplex real-time PCR they found 14.6% of samples were positive for adenovirus and 3.3% positive for herpes simplex 1 (HSV-1. The results for herpes simplex 2 (HSV-2 and varicella-Zoster (VZV were negative. In other investigations2,3 of viral conjunctivitis adenoviruses, HSV-1, HSV-2 and VZV have been reported to be the most important causes of viral conjunctivitis. The authors propose a more extensive investigation on number of patients and the emerging viruses particularly in this part of the world. Rahimi et al in their presentation “Clinical outcomes in acanthamoeba keratitis treated with polyhexamethylene biguanide as monotherapy” have studied 27 eyes of 25 patients presenting Acanthamoeba keratitis (AK. They emphasize the importance of confocal biomicroscopy to find the cysts or trophozoites of the amoeba, indicating 96.3% of positive results compared to 81.5% of positivity in the culture

  10. Effect of Simvastatin and Metformin on Aortic Configurational Changes and CD40/CD40L Expression in Atherosclerosis Rats%辛伐他汀和二甲双胍对动脉粥样硬化大鼠动脉构型及CD40/CD40L表达的影响

    Institute of Scientific and Technical Information of China (English)

    黄皓章; 黄露霜; 尹明景; 朱继金

    2013-01-01

    intervention mechanism. Methods A total of 50 healthy SD male rats, aged 8 weeks, weight about 200 g,were randomly divided into 5 groups( n = 10 ):Group N ( normal control group ),Group SF( high salt + high fat group ), Group ST( high fat plus high salt + simvastatin group ), Group MT( high fat plus high salt + metformin group ),Group ST +MT( high fat plus high salt + simvastatin + metformin group ). After 16-week feeding,the rats in each group were detected for blood lipid, aortic pathology and configuration, serum sCD40L level and the expression of CD40L in arterial tissue. Results ① Blood lipid:In Group SF,total cholesterol( TC ), triglyceride( TG ) were significantly higher than those in Group N( P 0. 05 );TC,TG in Group MT and Group ST + MT were significantly lower than those in Group N( P MT > ST > ST + MT ). The ratio of lumen area/total vascular area( LA/TV A ) in Group SF was smaller than those in Group N,Group ST,Group MT,Group ST + MT( P 0. 05 ). ④ Serum sCD40L level:In Group SF.the serum concentration of sCEMOL was higher than those in Group N,Group ST,Group MT and Group ST + MT( P 0.05 ). ⑤ Expression of CD40L in arterial tissues:The expression of CD40L in Group SF was higher than those in Group N, Group ST, Group MT and Group ST + MT( P 0. 05 ). Conclusion The level of serum sCD40L and expression of CD40L in arterial tissues increase in AS rats. Both simvastatin and metformin have an anti-atherosclerosis effect by reducing blood lipid, inhibiting the expression of CD40L and relieving inflammatory response. Biguanides drugs have a more significant effect for decreasing blood lipid while statins drugs are better in protecting vessel and improving AS. The combination of the two drugs above is superior to either of them in effect.

  11. A Research Report on the Prescription Rights of Chinese Nurses

    Institute of Scientific and Technical Information of China (English)

    Shi-Fan Han; Rui-Fang Zhu; Hui-Hui Han

    2015-01-01

    prescription related courses.Results:The physician is not considered to be the best decision-making main body of clinical nursing work and graded nursing,nurses can participate in the work of decision-making.The qualification of hierarchical decision-making nurse and nurse prescribing applicants have been determined.The hierarchical nursing decision-making nurses’ position description and training outline have been compiled.Experts suggest that clinical nurses with certain qualifications should be given the rights of some prescription form(independent prescription,prescription,prescription protocol extension) to prescribe specific drugs in high fever,hypoglycemia,hypertension,anaphylactic shock and other 11 specific circumstances.The nurses of the diabetes should be given the right of prescribing sulfonylureas,biguanides,glucosidase inhibitor,and protamine zinc insulin,and the right to write the prescription and consultation for part of medical equipment,health education,and four routine tests,which contains blood sugar monitoring,urine glucose monitoring,glycosylated hemoglobin assay,and oral glucose tolerance test.Tumor specialist nurses should be given the right to write the prescription of 7 specific circumstances including blood routine tests,electrocardiogram,blood biochemistry and other 9 laboratory tests,constipation,phlebitis,and cancer pain,and the right of 5 tumor emergency prescription including chemotherapy drug allergy,hemorrhagic shock,acute upper gastrointestinal bleeding.Nurses in emergency department with certain qualification should be given the right to prescribe specific drugs in 15 circumstances which include cardiac arrest,ventricular fibrillation,and acute cardiogenic chest pain.Community nurses with certain qualification should be given the right to write the prescriptions on 14 contents including disinfection and cleaning,sterile infusion type,and wound care products.Experts suggest that nursing undergraduate education in China should be added with

  12. Glycemic control in 374 outpatients with type 2 diabetes mellitus%门诊2型糖尿病患者374例代谢控制现状

    Institute of Scientific and Technical Information of China (English)

    杨露; 陆建灿; 丁长花; 胡艳艳; 黄勤

    2013-01-01

    %). Participants with body mass index ( BMI) less than 24 kg/mz achieved better glycemic control compared with those with BMI more than 24 kg/m2(P<0. 05). Sulphonylureas and biguanides were the most commonly used options, accounting for 51. 35% in the two drug group and 71. 09% in the three or more drug group. The proportion of participants with poorly controlled glycemic status (HbA1c≥8. 0%) in the three or more drug group (34. 12%) was significantly higher than that of participants in the other two groups (20. 86% , P = 0. 005). Logistic regression analysis indicated that the long course of disease (OR= 1. 64), high BMI (OR=1. 60) and the more comorbidities and complications (OR=l. 60) were the risk factors of poor glycemic control (all P<0. 01), and age was a protective factor for glycemic control (OR = 0. 695, P<0. 01). Conclusion The status of blood glucose control in the outpatients of our hospital is not satisfactory, which is due to factors such as "therapeutic inertia". When multidrug therapy fails to achieve the recommended glycemic targets, the treatment strategy should be adjusted promptly.

  13. Analysis on the adverse drug reaction signal and its impact factors induced by oral hypoglycemic agents%口服抗糖尿病药物不良反应信号及其相关因素分析

    Institute of Scientific and Technical Information of China (English)

    柯俊; 汤文璐; 薛浩; 庞露微

    2012-01-01

    ,but new ADR reports marked as moderate and severe which were not recorded in drug instructions and references increased significantly during the period of 2009 to 2010,and the most frequently involved agents were biguanides and sulfonylureas (SU).The logistic regression analysis of ADR and its influence factors showed female,the high frequency of taking drug and single medication were risk factors of gastrointestinal damage,weight was the risk factor of skin damage,and combined medication and patients' age were the risk factors of hypoglycemia caused by SU.The results of measures of disproportionality found some ADR signals induced by OHAs.CONCLUSION The ADR of oral hypoglycemic agents could involve multiple systems and organs.Risk factors such as gender,age,weight,frequency of taking drug and drug combination had effects on the occurrence of ADR in different degree,so in order to take OHAs safely and reasonably,we should strengthen the ADR monitoring and put emphasis on controlling the risk factors of ADR in clinical practice.

  14. A Research Report on the Prescription Rights of Chinese Nurses☆

    Institute of Scientific and Technical Information of China (English)

    Shi-Fan Han; Rui-Fang Zhu; Hui-Hui Han

    2015-01-01

    undergraduate added with nurse authority of prescription related courses. Results: The physician is not considered to be the best decision-making main body of clinical nursing work and graded nurs-ing, nurses can participate in the work of decision-making. The qualification of hierarchical decision-making nurse and nurse prescribing applicants have been determined. The hierarchical nursing decision-making nurses’ position description and training outline have been compiled. Experts suggest that clinical nurses with certain qualifications should be given the rights of some prescription form ( independent prescription, prescription, prescription protocol extension) to prescribe specific drugs in high fe-ver, hypoglycemia, hypertension, anaphylactic shock and other 11 specific circumstances. The nurses of the diabetes should be given the right of prescribing sulfonylureas, biguanides, glucosidase inhibitor, and protamine zinc insulin, and the right to write the prescription and consultation for part of medical equipment, health education, and four routine tests, which contains blood sugar monitoring, urine glucose monitoring, glycosylated hemoglobin assay, and oral glucose tolerance test. Tumor specialist nurses should be given the right to write the prescription of 7 specific circumstances including blood routine tests, electrocardio-gram, blood biochemistry and other 9 laboratory tests, constipation, phlebitis, and cancer pain, and the right of 5 tumor emer-gency prescription including chemotherapy drug allergy, hemorrhagic shock, acute upper gastrointestinal bleeding. Nurses in e-mergency department with certain qualification should be given the right to prescribe specific drugs in 15 circumstances which include cardiac arrest, ventricular fibrillation, and acute cardiogenic chest pain. Community nurses with certain qualification should be given the right to write the prescriptions on 14 contents including disinfection and cleaning, sterile infusion type, and wound care

  15. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Science.gov (United States)

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after

  16. Effects of low-fat diet on body mass, blood lipids and sugar control in obese patients with type 2 diabetes mellitus%低脂肪饮食对肥胖2型糖尿病患者体质量、血脂及血糖的影响

    Institute of Scientific and Technical Information of China (English)

    曹爱华; 尚艳菲; 辛波

    2012-01-01

    Objective To study the effects of low-fat diet on body mass,blood lipids and sugar in obese patients with type 2 diabetes mellitus(T2DM). Methods 120 obese patients with T2DM were randomized to the two groups, research groups60 obese patients with T2MD got routine treatment of low-fat associated with biguanides diet,control group:60 obese patients with T2MD were advised on the treatment of the routine diabetic diet. Outcome measures of body mass, HbA1 c, blood pressure and blood lipids were obtained before and after treatment. Results After one year of treatment,body mass and HbA, c in research group reduced by (6. 6± 1. 4) kg and (2.8±0. 3) % ,and those in control group reduced by (3. 4±1. 2) kg,(l. 0±0. 2)%( P <0. 05). Before treatment.TC and LDL-C in research group were (4.44±0. 82) mmol/L and (2. 56±0. 61) mmol/L,and those in control group were (4. 38±0. 84) mmoI/L and (2. 54± 0. 70) mmol/L. After treatment.TC and LDL-C in research group were (3.90±0. 73) mmol/L,(2. 04±0.62) mmol/L,and those in control group were (4. 26 ± 0. 72) mmol/L, (2. 48 ± 0. 65) mmol/L, and two groups showed statistical significance after treatment P <0. 05). Conclusion Low-fat diet can improve body mass, HbA,c,TC and LDL-C of T2DM patients and curative effect is better than the conventional control group, and it is an effective way in the treatment of obese patients with T2DM.%目的 观察低脂肪饮食对肥胖2型糖尿病患者体质量、血脂和血糖的影响.方法 120例肥胖2型糖尿病患者随机分配至低脂肪饮食+双胍类药物治疗组(实验组)和常规糖尿病饮食+双胍类药物治疗组(对照组),各60倒.在治疗前及治疗1年后检测两组患者的体质量(BM)、糖化血红蛋白(HbA1c)、血压和血脂.结果 治疗1年后,实验组与对照组BM分别下降(6.6±1.4)kg和(3.4±1.2)kg,HbA1c分别下降(2.8±0.3)%和(1.0±0.2)%(P<0.05);实验组治疗前总胆固醇(TC)为(4.44±0.82) mmol/L、低密度

  17. 亚洲来得时治疗达标研究(ATLAS)在中国2型糖尿病管理中的潜在价值:研究原理及设计%Potential value of the Asian Treat to Target Lantus Study (ATLAS) for the type 2 diabetes management in China: the rationale and design of ATLAS

    Institute of Scientific and Technical Information of China (English)

    潘长玉代表ATLAS中国研究组

    2011-01-01

    Asia and Russia patients with type 2 diabetes mellitus.Total 554 subjects are planned for this study and 160 subjects will be recruited in China.As one of the most important participating countries,China has some special characteristics in diabetes management,such as less self monitoring of blood glucose (SMBG),fewer self-titration and preferred premixed insulin in stead of basal insulin,et al.This report is aimed to introduce the study rationale and design of ATLAS with the situation in China.Methods Subjects (40-75 years old,body mass index ≥20 kg/m2 and ≤40 kg/m2 ) with type 2 diabetes mellitus for> 2 years,suboptimally controlled ( HbA1c ≥ 7.0% and ≤ 11.0% ) with stable doses of 2 oral anti-diabetic drugs (OADs) (sulphonylureas,biguanides,alpha-glucosidase inhibitors,DPP-IV inhibitors,and metiglinides)for>3 months,and not using insulin.The subjects will be randomized either to the patient-led or the physician-led titration arm for6 months treatment of glargine plus OADs regimen,where the insulin dose will be adjusted to achieve a target fasting plasma glucose value of 110 mg/dl (6.1 mmol/L).Study endpoints:The primary endpoint will be change in mean HbA1c at 6 months from baseline.For the primary endpoint,if non-inferiority is achieved using a HbA1c 0.3% boundary,superiority test will be undertaken.Secondary endpoints will include:proportion of patients reaching the target of HbA1c <7% with or without hypoglycemia; the number of patients whose HbA1c decreases at least 10% and/or 5% ; the change of fasting plasma glucose,postprandial plasma glucose,weight,dose of insulin glargine,patient treatment satisfaction,and quality of life in the two groups.Conclusions The ATLAS trial will provide information on the relative safety and efficacy of a patient-led versus physician led titration strategy for insulin glargine-based basal insulin initiation in patients who are not controlled with two OADs.The results of the study may provide new ideas and