Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

An efficient approach for conversion of 5-substituted 2-thiouridines built in RNA oligomers into corresponding desulfured 4-pyrimidinone products.

An efficient approach for the desulfuration of C5-substituted 2-thiouridines (R5S2U) bound in the RNA chain exclusively to 4-pyrimidinone nucleoside (R5H2U)-containing RNA products is proposed. This post-synthetic transformation avoids the preparation of a suitably protected H2U phosphoramidite, which otherwise would be necessary for solid-phase synthesis of the modified RNA. Optimization of the desulfuration, which included reaction stoichiometry, time and temperature, allowed to transform a set of ten R5S2U-RNAs into their R5H2U-RNA congeners in ca. 90% yield.

2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes.

2-Thiouracil-containing nucleosides are essential modified units of natural and synthetic nucleic acids. In particular, the 5-substituted-2-thiouridines (S2Us) present in tRNA play an important role in tuning the translation process through codon-anticodon interactions. The enhanced thermodynamic stability of S2U-containing RNA duplexes and the preferred S2U-A versus S2U-G base pairing are appreciated characteristics of S2U-modified molecular probes. Recently, we have demonstrated that 2-thiouridine (alone or within an RNA chain) is predominantly transformed under oxidative stress conditions to 4-pyrimidinone riboside (H2U) and not to uridine. Due to the important biological functions and various biotechnological applications for sulfur-containing nucleic acids, we compared the thermodynamic stabilities of duplexes containing desulfured products with those of 2-thiouracil-modified RNA and DNA duplexes. Differential scanning calorimetry experiments and theoretical calculations demonstrate that upon 2-thiouracil desulfuration to 4-pyrimidinone, the preferred base pairing of S2U with adenosine is lost, with preferred base pairing with guanosine observed instead. Therefore, biological processes and in vitro assays in which oxidative desulfuration of 2-thiouracil-containing components occurs may be altered. Moreover, we propose that the H2U-G base pair is a suitable model for investigation of the preferred recognition of 3'-G-ending versus A-ending codons by tRNA wobble nucleosides, which may adopt a 4-pyrimidinone-type structural motif.

In situ spectroscopic characterization of rectifying molecular monolayers self-assembled on gold.

We report visible, Raman, and infrared spectra of self-assembled monolayers (SAMs) formed by the donor-(pi-bridge)-acceptor chromophore, Z-beta-[N-(omega-acetylthioalkyl)-4-quinolinium]-alpha-cyano-4-styryldicyanomethanide (CH3CO-S-CnH2n-Q3CNQ where n=8, 10), on gold-coated substrates. The data are compared with the spectra collected for the same compound in solution and in the solid state, and with those obtained for a Langmuir-Blodgett (LB) monolayer of C16H33-Q3CNQ deposited on gold. Spectral analysis confirms that in solution, in the solid state and in the LB film the chromophore has a zwitterionic (D+-pi-A-) ground state. At variance with this well-known result, our data show that in SAMs deposited on gold the chromophore has a more neutral, quinoid ground state. We relate this difference to the different packing of the molecules in the two different films: in SAMs in fact the chromophores stand almost vertical with respect to the substrate, whereas in LB films they make an angle of about 45 degrees. The Q3CNQ molecule is a well-known molecular rectifier, and for SAMs we were able to check the direction of electron flow at forward bias on the same samples that have been characterized spectroscopically, shedding light on the rectification mechanism.

Molecular diodes and ultra-thin organic rectifying junctions: Au-S-CnH2n-Q3CNQ and TCNQ derivatives.

Attempts to obtain derivatives of the molecular diode, 2-{4-[1-cyano-2-(1-(omega-acetylsulfanylalkyl)-1H-quinolin-4-ylidene)-ethylidene]-cyclohexa-2,5-dienylidene}-malonitrile [1, CH(3)CO-S-C(n)H(2n)-Q3CNQ], from either 2,3,5,6-tetrafluoro-7,7,8,8-tetracyano-p-quinodimethane (TCNQF(4)) or 2,3,5,6-tetramethyl-7,7,8,8-tetracyano-p-quinodimethane (TMTCNQ) result in ring closure via the cyano group of the pi-bridge and yield di-substituted analogues: 2-{2,3,5,6-tetrafluoro-4-[6-(10-acetylsulfanyldecyl)-3-(1-(10-acetylsulfanyldecyl)-1H-quinolin-4-ylidenemethyl)-6H-benzo[f][1,7]naphthyridin-2-ylidene]-cyclohexa-2,5-dienylidene}-malonitrile (2a) and the 2,3,5,6-tetramethyl derivative (2b). Self-assembled monolayers (SAMs) of these donor-(pi-bridge)-acceptor molecular diodes exhibit asymmetric current-voltage characteristics with electron flow at forward bias from the top contact to surface C(CN)(2) groups. Comparison is made with I-V curves from ultra-thin films of an organic rectifying junction in which TCNQ(-) is electron-donating and a donor-(sigma-bridge)-acceptor diode in which TCNQ degrees is electron-accepting.

Controlled alignment of molecular diodes via ionic assembly of cationic donor-(pi-bridge)-acceptor molecules on anionic surfaces.

Alignment of cationic donor-(pi-bridge)-acceptor molecules via metathesis with a self-assembled monolayer formed from sodium 3-mercapto-1-propanesulfonate results in ultra-thin rectifying Au-S-(CH2)3SO3-/A+-pi-D structures which exhibit optimum current ratios of 450 at +/-1 V for N-methyl-5-(4-dibutylaminobenzylidene)-5,6,7,8-tetrahydroisoquinolinium.