Disease relevance of DIGUANIDE

• Chlorhexidine or polyhexamethylene biguanide for acanthamoeba keratitis [1].
• Because guanidino compounds can block dicarbonyl groups, we have investigated the effects of the diamino biguanide compound metformin and of hyperglycemia on MG and its detoxification products in type 2 diabetes [2].
• The effect of the hypoglycemic biguanide, phenformin, on the binding of insulin to MCF-7 cells, an in vitro line derived from a human breast cancer, has been investigated [3].
• Biguanide-associated lactic acidosis. Case report and review of the literature [4].
• CONCLUSIONS--Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency [4].

High impact information on DIGUANIDE

• Biguanide treatment increases the number of insulin-receptor sites on human erythrocytes [5].
• The effect of metformin, a dimethyl-substituted biguanide, known to lower plasma insulin and PAI-1 levels in vivo was concomitantly evaluated [6].
• BACKGROUND & AIMS: The biguanide drug metformin has recently been found to improve steatosis and liver damage in animal models and in humans with nonalcoholic steatohepatitis [7].
• The biguanide drug metformin stimulates AMP-activated protein kinase, a master regulator of cellular energy metabolism, and has antihyperglycemic activity due to attenuation of gluconeogenesis in hepatocytes and 2-fold stimulation of glucose transport by skeletal muscle [8].
• Metformin, an insulin-sensitizing biguanide, enhances peripheral insulin action and lowers blood pressure in hyperinsulinemic animals, but its direct impact on cardiac function is not fully understood [9].

Chemical compound and disease context of DIGUANIDE

• Outcome of acanthamoeba keratitis treated with polyhexamethyl biguanide and propamidine [10].
• We report here on an immunocompetent child with S. prolificans-associated osteomyelitis successfully treated with debridement, local irrigation with polyhexamethylene biguanide, and the systemic administration of voriconazole and caspofungin despite poor in vitro activity of voriconazole alone against the isolate [11].
• The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide [12].
• The combination of a thiazolidinedione and a biguanide reduces hyperglycemia, hyperinsulinemia, and insulin resistance and improves factors that have been implicated in the pathogenesis of cardiovascular complications [13].
• PURPOSE: To determine the efficacy of 0.02% polyhexamethylene biguanide and 1% povidone iodine in experimental keratitis [14].

Biological context of DIGUANIDE

• To directly assess the effects of the biguanide, metformin, on hepatic gluconeogenesis, it was added at high therapeutic levels (90 microg/ml) to the medium perfusing an isolated rat liver [15].
• Plasma biguanide levels are correlated with metabolic effects in diabetic patients [16].
• Killing acanthamoebae with polyaminopropyl biguanide: quantitation and kinetics [17].
• Phagocytosis affects biguanide sensitivity of Acanthamoeba spp [18].
• The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK [19].

Anatomical context of DIGUANIDE

• In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally) [20].
• The latter effect was additive to the maximum effect of metformin, suggesting that the biguanide stimulates hexose uptake into muscle cells by an insulin-independent mechanism [21].
• In contrast, the changes in intracellular Ca2+ concentration evoked by m-chlorophenyl biguanide displayed substantially slower kinetics, similar to previous findings, but which varied among responding synaptosomes from one region to another [22].
• Very high biguanide concentrations, applied infrequently, directly to the molars, effectively reduced caries and resulted in less staining [23].
• The effect of the hypoglycemic biguanide drug Metformin was investigated after a 72 h pretreatment of human cultured fibroblasts [24].

Associations of DIGUANIDE with other chemical compounds

• Metformin, a biguanide antihyperglycemic drug, has been shown to improve ovarian function and glucose metabolism in women with polycystic ovary syndrome (PCOS), but results concerning its effects on insulin sensitivity are controversial [25].
• We 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 [26].
• The molecular electrostatic potential (MESP) surfaces of neutral, protonated, and deprotonated biguanide have been shown to be similar in their most stable arrangements [27].
• Proguanil acted as a biguanide rather than as its metabolite cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the atovaquone effect; another DHFR inhibitor, pyrimethamine, also had no enhancing effect [28].
• The lethal effects of various biocides, in particular two agents (chlorhexidine diacetate and polyhexamethylene biguanide) on cysts and trophozoites of Acanthamoeba castellanii have been measured by both plaque assay and flow cytometry (FCM) [29].

Gene context of DIGUANIDE

• Enhanced secretion of glucagon-like peptide 1 by biguanide compounds [30].
• The biguanide metformin did not alter GLUT1 expression, glucose transport, fibronectin formation, or collagen metabolism, except at high concentrations [31].
• 5. The selective 5-HT3 agonist, 1-m-chlorophenyl biguanide, had no contractile effect on rat bronchus, whether transplanted or not [32].
• In this study, we investigated the effects of the thiazolidinedione, Ciglitazone, the peroxisome proliferator-activated receptor alpha-agonist 5,8,11,14-eicosatetraynoic acid (ETYA) and the biguanide, Metformin on interleukin-8 gene expression and production in human adipose tissue in vitro [33].
• Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics [34].

Analytical, diagnostic and therapeutic context of DIGUANIDE

• Interestingly, the microinjection of this biguanide, at a final concentration of 20 nmol/l, allowed a similar biochemical response [35].
• Discontinuation of biguanide treatment, or administration of antibiotics, normalized or improved the increased deconjugation of bile acids and the Schilling test [36].
• An expedient and facile one-step synthesis of a biguanide library by microwave irradiation coupled with simple product filtration. Inhibitors of dihydrofolate reductase [37].
• 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 [38].
• Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin [39].

References