Linagliptin (Trajenta): a selective DPP-4 inhibitor with limited renal elimination

peer reviewedLinagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and GIP ("Glucose-dependent Insulinotropic Polypeptide"). As other molecules belonging to this pharmacological class, linagliptin improves blood glucose control of type 2 diabetic patients, without increasing hypoglycaemic risk, without promoting weight gain and with a good clinical and biological tolerance profile. Both efficacy and safety have been demonstrated in randomized controlled trials as monotherapy or in combination with other glucose-lowering agents, independent of demographic or clinical patient's characteristics. The pharmacokinetics specificity of linagliptin comprises its biliary excretion, with low hepatic metabolism (no drug-drug interactions) and, in contrast to other gliptins, its negligible renal elimination. Because of these favourable properties, linagliptin may be used without dose adjustment (5 mg once a day) in patients with renal impairment, as well as in elderly people

Sugar: results of a Belgian observational study on the use of sitagliptin in patients with type 2 diabetes

peer reviewedSitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4, has been assessed in a large Belgian prospective observational study. The aim of the SUGAR study was to evaluate the efficacy of sitagliptin, at a dose of 100 mg once daily, when it was added in patients with uncontrolled type 2 diabetes followed in real life conditions. In the intent-to-treat population (n = 605), mean glycated haemoglobin level decreased from 8.41 +/- 1.18% to 7.29 +/- 0.86% after a follow up averaging 110 days (p < 0.0001). Similarly, mean fasting plasma glucose level decreased from 180 +/- 50 mg/dl to 141 +/- 37 mg/ dl (p < 0.0001). The improvement of these two parameters was observed independently of basal demographic characteristics, but was directly influenced by baseline initial corresponding values. The vast majority of patients included in SUGAR were initially treated by metformin as monotherapy (current criterion for sitagliptin reimbursement in Belgium); metformin daily dose slightly decreased when sitagliptin was added (from 1975 +/- 681 mg to 1919 +/- 667 mg; p = 0.033). Patients receiving other glucose-lowering agents, as single or combined therapies, had also a significant alleviation of their treatment when sitagliptin was added. After 3-6 months of follow up, more than 95% of patients still received sitagliptin, arguing for both the efficacy and the good tolerance of this new oral antidiabetic agent in clinical practice

Kinetics of photocatalytic removal of 2-amino-5-chloropyridine from water

Titanium dioxide sensitized photocatalytic degradation of a pyridine pesticide analogue, 2-amino-5-chloropyridine, was investigated by monitoring the pyridine moiety degradation, as well as by monitoring the chloride generated in the process. Effect of the initial substrate concentration on the rate of its degradation is reported. Here we show that the kinetics of both reactions are of the zero-order in the entire investigated concentration range. The Langmuir-Hinshelwood kinetic model successfully described the influence of the initial substrate concentration on the rate of the pyridine moiety degradation. It was found that dechlorination of the substrate takes place by direct photolysis. The differences in the kinetics of pyridine moiety degradation and dechlorination were explained on the basis of the electrostatic potential for the investigated compound

Act quickly, decide later: long latency visual processing underlies perceptual decisions but not reflexive behavior

Jolij J, Scholte H, Van Gaal S, Hodgson TL, Lamme VAF (2011) Act quickly, decide later: Long latency visual processing underlies perceptual decisions but not reflexive behavior. Journal of Cognitive Neuroscience 23(12), p 3734-3745

Refractive changes following surgery for correction of esotropia

Purpose: To evaluate changes in refraction and corneal curvature following surgery for correction of acquired esotropia. Methods: 42 eyes of 21 patients with acquired moderate angle esotropia without any other form of strabismus were prospectively enrolled and submitted to a complete ophthalmological examination followed by recess/resect procedure in a single eye. Data from the fellow eye were selected as control. Ophthalmological assessment was carried out preoperatively, 1 month after surgery and 6 months after surgery, where astigmatism was compared using vector analysis and the polar value concept. Results: The eyes submitted to surgery revealed a significant (p<0.05) decrease in spherical equivalent, from 3.28 ± 1.98 diopters to 3.05 ± 1.95 diopters. Refraction data disclosed a significant increase in the 90° component of net astigmatism, from 0.458 ± 0.594 diopters to 1.002 ± 0.718 diopters, which was also observed in keratometric readings:1.083 ± 0.560 diopters to 1.690 ± 0.591 diopters. Surgically induced astigmatism, assessed using refraction data was 0.63 ± 0.27 diopters at an average axis of 92.30 ± 14.91 degrees, and 0.71 ± 0.27 diopters at an average axis of 94.45 ± 15.69 degrees as obtained by keratometric readings. This is visually demonstrated by the corneal topography difference map. Conclusions: There is a statistically significant and clinically relevant increase in with-the-rule astigmatism in esotropic patients submitted to monocular recess/resect surgery. This change is stable at a 6 month follow-up and is associated with a decrease in mean spherical equivalent.Objetivo: Estudar o comportamento da refração e da curvatura corneana em pacientes com esotropia essencial submetidos à cirurgia monocular para correção do estrabismo. Métodos: Estudo prospectivo em que 42 olhos de 21 pacientes com esotropia essencial de ângulo moderado, sem quaisquer outros estrabismos associados, foram selecionados e submetidos ao exame oftalmológico completo e à cirurgia monocular. O olho contralateral serviu como grupo controle. Foram feitas avaliações de pré-operatório, pós-operatório de 1 mês e pós-operatório de 6 meses. O astigmatismo pré-operatório foi confrontado com os astigmatismos pós-operatórios por análise vetorial e cálculo do valor polar. Resultados: Obtivemos, nos olhos operados, redução significante (p<0,05) na médio do equivalente esférico, de 3,28 ±1,98 dioptrias para 3,05 ± 1,95 dioptrias. Na refração houve um aumento significante da média do componente a 90° do astigmatismo, de 0,458 ± 0,594 dioptrias para 1,002 ± 0,718 dioptrias, também observado na ceratometria: 1,083 ± 0,560 dioptrias para 1,690 ± 0,591 dioptrias. A média do astigmatismo induzido pela cirurgia, na refração, foi de 0,63 ± 0,27 dioptrias a um eixo médio de 92,30 ± 14,91 graus e de 0,71 ± 0,27 dioptrias a um eixo médio de 94,45 ± 15,69 graus na ceratometria, evidenciáveis graficamente pelo mapa diferencial da topografia corneana. Conclusões: Observa-se aumento estatisticamente significante e clinicamente relevante do astigmatismo a-favor-da-regra em pacientes esotrópicos submetidos ao retrocesso/ressecção monocular. Essa mudança é estável ao longo do tempo e é acompanhada de diminuição significante do equivalente esférico.Faculdade de Medicina da Universidade de São Paulo Hospital das Clínicas Departamento de OftalmologiaSanta Casa de São Paulo Departamento de OftalmologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de OftalmologiaUNIFESP, EPM, Depto. de OftalmologiaSciEL

Medication of the month...Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents

peer reviewedExenatide (Byetta) is a synthetic derivative of exendin-4 and an agonist of receptors of glucagon-like peptide-1 (GLP-1). It is resistant to the rapid inactivation by dipeptidylpeptidase-4 and acts as an incretin mimetic. It stimulates insulin secretion by the B cell in a glucose-dependent manner whereas it inhibits glucagon secretion. Exenatide improves mainly postprandial glucose concentrations and lowers glycated haemoglobin (HbA(1c)) levels, without being directly responsible for hypoglycaemia or requiring mandatory home blood glucose monitoring. Furthermore, it slows down gastric emptying and promotes sustained body weight reduction, even in absence of frequently reported nausea following treatment initiation. Exenatide is recommended and reimbursed in Belgium for the treatment of type 2 diabetes, in combination with metformin and a sulfonylurea, in patients not adequately controlled with maximal tolerated doses of these oral glucose-lowering agents. Exenatide is presented as pre-filled pens for subcutaneous injection. The recommended initial dose is 5 microg before morning and evening meals, to be up titrated to 10 microg twice daily. Exenatide may represent a valuable alternative to insulin therapy, especially in overweight or obese patients with type 2 diabetes and not ready to perform home blood glucose monitoring

Manipulating word awareness dissociates feed-forward from feedback models of language-perception interactions

Previous studies suggest that linguistic material can modulate visual perception, but it is unclear at which level of processing these interactions occur. Here we aim to dissociate between two competing models of language–perception interactions: a feed-forward and a feedback model. We capitalized on the fact that the models make different predictions on the role of feedback. We presented unmasked (aware) or masked (unaware) words implying motion (e.g. “rise,” “fall”), directly preceding an upward or downward visual motion stimulus. Crucially, masking leaves intact feed-forward information processing from low- to high-level regions, whereas it abolishes subsequent feedback. Under this condition, participants remained faster and more accurate when the direction implied by the motion word was congruent with the direction of the visual motion stimulus. This suggests that language–perception interactions are driven by the feed-forward convergence of linguistic and perceptual information at higher-level conceptual and decision stages