Heart failure and diabetes mellitus: insight into comorbidity

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities with a bidirectional relationship. Patients with HF have increased risk of developing DM, and those with DM are at greater risk of developing HF. HF does not fit clearly into the microangiopathy and macroangiopathy groups. It is known that coronary artery disease and arterial hypertension are the major causes of HF; however, it has been shown that DM can trigger functional and structural abnormalities in the myocardium via diabetic cardiomyopathy, a condition with either restrictive or dilated phenotype. While HF treatment is equally effective and safe in patients with and without DM, this statement is not applicable for antidiabetic treatment. Several antidiabetic drugs, such as rosiglitazone, pioglitazone and saxagliptin increase the risk of hospitalisation for HF, therefore these antidiabetic drugs are contraindicated in patients with DM and HF or patients at risk of developing HF. Despite a large number of clinical evidence, uncertainty about the safety of antidiabetic drugs in patients with HF always exists. In this review, the issues of DM treatment in patients with HF are addressed in detail

Perceptions of Foreign Language Teachers for M-Learning

Educational technology is a set of systems consisting of tech savvy equipment, processes and methods for the effective and positive implementation of educational theories. Nowadays, when the internet is becoming widespread, and mobile device technologies such as smartphones and tablets have been developing rapidly, it is possible to access educational content without being connected to a place. Today, almost everyone has smartphones. Many social networks, sites, applications are available. Many studies have shown that technology is effective in the field of education. For teachers with foreign language and their perceptions of learning through the help of technology are important. In this study, it is important to determine teachers' perception levels of mobile applications that contribute to foreign language learning. The "mobile learning perception scale" developed to access the research data. Items that are mentioned in the scale are basically positive question, "absolutely disagree", "disagree", "undecided", "agree", "strongly agree". After analysing the reliability of the survey, the overall result was found as Cronbach ? = 0,963. A total of 180 teachers attended from North Cyprus and Russian universities. According to the result of the research, the teachers' perception of mobile learning is high. But this rate is proportional to age. There is a difference in the findings regarding the use of mobile technology when looking at the professional seniority and age ranges. This is due to the fact that recently, technology-supported trainings have been increased and the addition of "material design courses" and "technology-supported trainings" at universities play an important role in increasing perceptions. The use of mobile technology can be increased by providing in-service trainings to teachers with high professional experience and ages

Structure of Cyclic Nucleoside Phosphonate Ester Prodrugs: An Inquiry

The configuration at phosphorus in cyclic (<i>S</i>)-HPMPC (<b>1</b>, cidofovir) and (<i>S</i>)-HPMPA (<b>2</b>) phenyl ester (<b>5</b> and <b>6</b>, respectively) diastereomers (<b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b>, <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>) was determined by X-ray crystallography and correlated to their ¹H and ³¹P NMR spectra in solution. <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b> and <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> is (<i>a</i>, <i>a</i>) in the crystal and exists largely as an equilibrium of (<i>a</i>, <i>a</i>)/(<i>e</i>, <i>e</i>) conformers in chloroform or acetonitrile

Structure of Cyclic Nucleoside Phosphonate Ester Prodrugs: An Inquiry

The configuration at phosphorus in cyclic (<i>S</i>)-HPMPC (<b>1</b>, cidofovir) and (<i>S</i>)-HPMPA (<b>2</b>) phenyl ester (<b>5</b> and <b>6</b>, respectively) diastereomers (<b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b>, <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>) was determined by X-ray crystallography and correlated to their ¹H and ³¹P NMR spectra in solution. <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b> and <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> is (<i>a</i>, <i>a</i>) in the crystal and exists largely as an equilibrium of (<i>a</i>, <i>a</i>)/(<i>e</i>, <i>e</i>) conformers in chloroform or acetonitrile

Structure of Cyclic Nucleoside Phosphonate Ester Prodrugs: An Inquiry

The configuration at phosphorus in cyclic (<i>S</i>)-HPMPC (<b>1</b>, cidofovir) and (<i>S</i>)-HPMPA (<b>2</b>) phenyl ester (<b>5</b> and <b>6</b>, respectively) diastereomers (<b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b>, <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b>) was determined by X-ray crystallography and correlated to their ¹H and ³¹P NMR spectra in solution. <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>5</b> and <b>(</b><i><b>R</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, <b>(</b><i><b>S</b></i>_<b>p</b><b>)</b><i><b>-</b></i><b>6</b> is (<i>a</i>, <i>a</i>) in the crystal and exists largely as an equilibrium of (<i>a</i>, <i>a</i>)/(<i>e</i>, <i>e</i>) conformers in chloroform or acetonitrile

β,γ-CHF- and β,γ-CHCl-dGTP Diastereomers: Synthesis, Discrete ³¹P NMR Signatures, and Absolute Configurations of New Stereochemical Probes for DNA Polymerases

Deoxynucleoside 5′-triphosphate analogues in which the β,γ-bridging oxygen has been replaced with a CXY group are useful chemical probes to investigate DNA polymerase catalytic and base-selection mechanisms. A limitation of such probes has been that conventional synthetic methods generate a mixture of diastereomers when the bridging carbon substitution is nonequivalent (X ≠ Y). We report here a general solution to this long-standing problem with four examples of β,γ-CXY dNTP diastereomers: (<i>S</i>)- and (<i>R</i>)-β,γ-CHCl-dGTP (<b>12a-1</b>/<b>12a-2</b>) and (<i>S</i>)- and (<i>R</i>)-β,γ-CHF-dGTP (<b>12b-1</b>/<b>12b-2</b>). Central to their preparation was conversion of the prochiral parent bisphosphonic acids to the P,C-dimorpholinamide derivatives <b>7</b> of their (<i>R</i>)-mandelic acid monoesters, which provided access to the individual diastereomers <b>7a-1</b>, <b>7a-2</b>, <b>7b-1</b>, and <b>7b-2</b> by preparative HPLC. Selective acidic hydrolysis of the P–N bond then afforded “portal” diastereomers, which were readily coupled to morpholine-activated dGMP. Removal of the chiral auxiliary by H₂ (Pd/C) gave the four individual diastereomeric nucleotides <b>12</b>, which were characterized by ³¹P, ¹H, and ¹⁹F NMR spectroscopy and by mass spectrometry. After treatment with Chelex-100 to remove traces of paramagnetic ions, at pH ∼10 the diastereomer pairs <b>12a</b>,<b>b</b> exhibit discrete P_α and P_β ³¹P resonances. The more upfield P_α and more downfield P_β resonances (and also the more upfield ¹⁹F NMR resonance in <b>12b</b>) are assigned to the <i>R</i> configuration at the P_β-CHX-P_γ carbons on the basis of the absolute configurations of the individual diastereomers as determined from the X-ray crystallographic structures of their ternary complexes with DNA and polymerase β

Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia

The protective effects of recombinant human lactoferrin rhLF (branded &ldquo;CAPRABEL&trade;&rdquo;) on the cognitive functions of rat offspring subjected to prenatal hypoxia (7% O2, 3 h, 14th day of gestation) have been analyzed. About 90% of rhLF in CAPRABEL was iron-free (apo-LF). Rat dams received several injections of 10 mg of CAPRABEL during either gestation (before and after the hypoxic attack) or lactation. Western blotting revealed the appearance of erythropoietin (EPO) alongside the hypoxia-inducible factors (HIFs) in organ homogenates of apo-rhLF-treated pregnant females, their embryos (but not placentas), and in suckling pups from the dams treated with apo-rhLF during lactation. Apo-rhLF injected to rat dams either during pregnancy or nurturing the pups was able to rescue cognitive deficits caused by prenatal hypoxia and improve various types of memory both in young and adult offspring when tested in the radial maze and by the Novel Object Recognition (NOR) test. The data obtained suggested that the apo-form of human LF injected to female rats during gestation or lactation protects the cognitive functions of their offspring impaired by prenatal hypoxia

Effect of β,γ-CHF- and β,γ-CHCl-dGTP Halogen Atom Stereochemistry on the Transition State of DNA Polymerase β

Recently, we synthesized the first individual β,γ-CHX-dGTP diastereomers [(<i>R</i>)- or (<i>S</i>)-CHX, where X is F or Cl] and determined their structures in ternary complexes with DNA polymerase β (pol β). We now report stereospecificity by pol β on the mixed β,γ-CHX diastereomer pairs using nuclear magnetic resonance and on the separate diastereomers using transient kinetics. For both the F and Cl diastereomers, the <i>R</i> isomer is favored over the <i>S</i> isomer for G·C correct incorporation, with stereospecificities [(<i>k</i>_pol/<i>K</i>_d)_<i>R</i>/(<i>k</i>_pol/<i>K</i>_d)_<i>S</i>] of 3.8 and 6.3, respectively, and also for G·T misincorporation, with stereospecificities of 11 and 7.8, respectively. Stereopreference for the (<i>R</i>)-CHF-dGTP diastereomer was abolished for <i>k</i>_pol but not <i>K</i>_d with mutant pol β (R183A). These compounds constitute a new class of stereochemical probes for active site interactions involving halogen atoms. As Arg183 is unique in family X pols, the design of CXY deoxyribonucleotide analogues to enhance interaction is a possible strategy for inhibiting BER selectively in cancer cells