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Abstract Objective: To evaluate the effect of different pressures of an oral irrigation device (OID) and the irrigation solution type on the surface roughness of the giomer restorative material. Material and Methods: In this in vitro study, disk-shaped giomer samples were fabricated and assigned to 5 groups (n=23): Group 1, storage in distilled water (control); Group 2, OID #7 pressure/ water; Group 3, OID #10 pressure/ water; Group 4, OID #7 pressure/ 0.05% CHX; Group 5, OID #10 pressure/ 0.05% CHX. The samples' treatment simulated a one-year application of OID. Surface roughness (Ra) and topography of the giomer were evaluated using profilometry and scanning electron microscopy. The data were analyzed with Paired t-test, Tukey, and ANOVA tests (α=0.05). Results: The Ra of the samples increased significantly after treatment with OID (p<0.001). The roughness increase in groups with a pressure of 10 was higher than those with a pressure of 7 (p<0.001). The effect of pressure on surface changes was significant (p<0.001). However, the solution type and the cumulative effect of these two factors were insignificant (p=0.08 and p=0.43, respectively). Conclusion: Oral irrigation device with both solutions significantly increased the surface roughness and topographic changes of the giomer. The severity of these changes was related to the device's pressure.

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Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin's anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.

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The development of clinically viable metformin analogs is a challenge largely to be overcome. Despite being an extremely efficient drug for the treatment of type 2 diabetes mellitus, multiple studies were conducted seeking to improve its hypoglycemic activity or to ameliorate aspects such as low oral absorption and the incidence of gastrointestinal side effects. Furthermore, efforts have been made to attribute new activities, or even to expand the pre-existing ones, that could enhance its effects on diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this paper, we describe the analogs of metformin developed in the last three decades, highlighting the lack of computationally based rational approaches to guide their development. We also discuss this is probably a consequence of how unclear the mechanism of action of the parent drug is and highlight the recent advances towards the establishment of the main molecular target(s) for metformin. We also explored the binding of metformin, buformin and phenformin to the mitochondrial respiratory chain complex I through molecular docking analyses and reviewed the prospects of applying computational tools to improve the success in the development of such analogs. Therefore, it becomes evident that the wide range of molecular targets and the multiple activities displayed by metformin make this drug a promising prototype for developing novel entities, particularly for treating type 2 diabetes mellitus.

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The present study tested the hypothesis that acute metformin would increase peak power measured during a Wingate test. Fourteen men (24 ± 6 years; 75.8 ± 10.2 kg; 177 ± 7 cm) participated in four test sessions, conducted in a crossover, counterbalanced, double-blind model. The first and second sessions consisted of anthropometric measurements and one Wingate test per day to assess test-retest reliability. In the last two sessions, the Wingate tests were performed on metformin (500 mg capsule, 1 hour before) or placebo (cellulose capsule, 1 hour before) condition. No differences were found between the placebo and metformin for peak power (1056.8 ± 215.8 W vs. 1095.2 ± 199.3 W, respectively; p = 0.24). Mean power (630.9 ± 87.8 W vs. 613.1 ± 94.8 W, respectively; p=0.01) and total work (18928 ± 2633 kJ vs. 18393 ± 2845 kJ, respectively; p = 0.01) in the metformin condition were higher than the placebo. The power were greater in metformin when compared to the placebo in moments 3 (p = 0.01), 4 (p = 0.01), 5 (p = 0.04), 6 (p = 0.04), 7 (p = 0.02), 8 (p = 0.03) and 9 (p = 0.01) seconds. There were no differences between conditions for the peak lactate (p = 0.08) and the rating of perceived exertion (p = 0.84). Acute metformin administration increased the early power phase and the mean power of a Wingate test.

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The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients' response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments.

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OBJECTIVE: The aim of this double-blind randomized clinical trial was to assess whether the presence of alcohol in chlorhexidine gluconate mouthwashes influences their antimicrobial potential against salivary bacteria in young adults. Additionally, the taste perception was assessed. MATERIALS AND METHODS: In a randomized crossover design, 20 participants (17 women and three men; aged 18-38 years old) rinsed with the 0.12% chlorhexidine gluconate with (CHX+) or without alcohol (CHX-) for 1 min. Sterile flavoured-mint physiological saline was used as control solution. All participants rinsed with the assigned products only once with a period of at least 7 days of washout in between. For antimicrobial potential assay, stimulated saliva samples were collected from participants and had their total viable bacteria determined before and after each rinse. For taste perception assay, a visual analogue scale (VAS) was used to evaluate the taste perception after each rinse. Friedman followed by Wilcoxon tests and Bonferroni correction were performed. A P-value <0.017 was considered as statistically significant. RESULTS: The median per cent reduction in groups CHX+ and CHX- was 16.07 and 12.87, respectively. No statistically significant difference was found between these groups (P = 0.09). Regarding the gustatory perception, the VAS median values in groups CHX+ and CHX- were 3.50 and 5.50. No statistically significant difference was found in this outcome (P = 0.052). CONCLUSIONS: The presence of the alcohol on the formulation of gluconate chlorhexidine mouthwashes does not seem to interfere with their antimicrobial potential and with their taste perception.

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Acanthamoeba keratitis is a sight-threatening infectious disease. Resistance of the cystic form of the protozoan to biocides and the potential toxicity of chemical compounds to corneal cells are the main concerns related to long-term treatment with the clinically available ophthalmic drugs. Currently, a limited number of recognized antimicrobial agents are available to treat ocular amoebic infections. Topical application of biguanide and diamidine antiseptic solutions is the first-line therapy. We consider the current challenges when treating Acanthamoeba keratitis and review the chemical properties, toxicities, and mechanisms of action of the available biocides. Antimicrobial therapy using anti-inflammatory drugs is controversial, and aspects related to this topic are discussed. Finally, we offer our perspective on potential improvement of the effectiveness and safety of therapeutic profiles, with the focus on the quality of life and the advancement of individualized medicine.

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BACKGROUND: We do not know whether differences exist between the residual effect of 2% chlorhexidine in 70% isopropyl alcohol when compared with 1% triclosan in 70% isopropyl alcohol. METHODS: Using an analytic, longitudinal, controlled, and comparative experimental trial, with blinded measurements, we recruited healthy, adult volunteers from the University of Guanajuato who completed a stabilization phase of skin microbiota and had no history of skin allergies. Four 25-cm2 areas of the inner surface of the forearms were designated for study: unscrubbed control for establishing baseline bacterial counts, scrubbed control with tridistilled water, scrubbed with chlorhexidine, and scrubbed with triclosan. Quantitative cultures were taken of all the areas at 0, 3, and 24 hours, using agar plates with neutralizing agents. RESULTS: A total of 135 healthy volunteers were tested. At 24 hours, the unscrubbed control counts were 288 CFU/cm2, whereas the scrubbed control counts were 96 CFU/cm2; 24 CFU/cm2 for chlorhexidine and 96 CFU/cm2 for triclosan (Kruskal-Wallis χ2H = 64.27; P <.001). CONCLUSIONS: Chlorhexidine is the best antiseptic option when a prolonged antiseptic effect is needed; for instance, when implanting medical devices or performing surgical procedures.

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The aim of this study was to determine the ergogenic effects of metformin in high-intensity exercise, as well as its effects on anaerobic capacity, in healthy and physically active men. Ten subjects (mean (± standard deviation) maximal oxygen uptake (V˙O2max ) 38.6 ± 4.5 mL/kg per min) performed the following tests in a cycle ergometer: (i) an incremental test; (ii) six submaximal constant workload tests at 40%-90% (V˙O2max ); and (iii) two supramaximal tests (110% (V˙O2max ). Metformin (500 mg) or placebo was ingested 60 min before the supramaximal test. There were no significant differences between the placebo and metformin groups in terms of maximum accumulated oxygen deficit (2.8 ± 0.6 vs 3.0 ± 0.8 L, respectively; P = 0.08), lactate concentrations (7.8 ± 2.6 vs 7.5 ± 3.0 mmol/L, respectively; P = 0.75) or O2 consumed in either the last 30 s of exercise (40.4 ± 4.4 vs 39.9 ± 4.0 mL/kg per min, respectively; P = 0.35) or the first 110 s of exercise (29.0 ± 2.5 vs 29.5 ± 3.0 mL/kg per min, respectively; P = 0.42). Time to exhaustion was significantly higher after metformin than placebo ingestion (191 ± 33 vs 167 ± 32 s, respectively; P = 0.001). The fast component of V˙O2 recovery was higher in the metformin than placebo group (12.71 vs 12.18 mL/kg per min, respectively; P = 0.025). Metformin improved performance and anaerobic alactic contribution during high-intensity exercise, but had no effect on overall anaerobic capacity in healthy subjects.

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With the objective of characterizating lhe ocurrence of "red leg" in Minas Gerais, Brazill, young and adult frogs which presented in theirpads and limbs hemorragie in the skin of the ventral region, incordination, high death rate in adults and hepatic abscess at necropsy, have been evaluated. In fragment culture ofdamage skin and abscess, Aeromonas. hydrophila hás been isolated and identified. The bactericidal effect of VANTOCIL IB® was higher than that of potassium permanganate, as determinated by the minimal inhibitory concentration for isolated colonies.

Com o objetivo da caracterização da ocorrência de "red leg" em Minas Gerais, avaliaram-se rãs jovens e adultas que apresentavam úlceras nas patas e dedos, derrame hemorrágico na pele da região ventral, incoordenação motora, altas taxas de mortalidade em adultos e abscessos hepáticos à necropsia. No cultivo de fragmentos de pele lesada e abscessos, foi isolado e identificado Aeromonas hydrophila. O efeito bactericida do VANTOCIL IB® foi superior ao permanganato de potássio, determinado pela concentração inibitória mínima para colónias isoladas.

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With the objective of characterizating lhe ocurrence of "red leg" in Minas Gerais, Brazill, young and adult frogs which presented in theirpads and limbs hemorragie in the skin of the ventral region, incordination, high death rate in adults and hepatic abscess at necropsy, have been evaluated. In fragment culture ofdamage skin and abscess, Aeromonas. hydrophila hás been isolated and identified. The bactericidal effect of VANTOCIL IB® was higher than that of potassium permanganate, as determinated by the minimal inhibitory concentration for isolated colonies.

Com o objetivo da caracterização da ocorrência de "red leg" em Minas Gerais, avaliaram-se rãs jovens e adultas que apresentavam úlceras nas patas e dedos, derrame hemorrágico na pele da região ventral, incoordenação motora, altas taxas de mortalidade em adultos e abscessos hepáticos à necropsia. No cultivo de fragmentos de pele lesada e abscessos, foi isolado e identificado Aeromonas hydrophila. O efeito bactericida do VANTOCIL IB® foi superior ao permanganato de potássio, determinado pela concentração inibitória mínima para colónias isoladas.