Hydroxyurea-Lactose Interaction Study: In Silico and In Vitro Evaluation.

The Maillard reaction between hydroxyurea (a primary amine-containing drug) and lactose (used as an excipient) was explored. The adduct of these compounds was synthesized by heating hydroxyurea with lactose monohydrate at 60 °C in borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV-visible spectroscopy and Fourier transform infrared, differential scanning calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry studies. An in silico investigation of how the adduct formation affected the interactions of hydroxyurea with its biological target oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal hemoglobin synthesis, was carried out. The in silico evaluations were complemented by an in vitro assay of the anti-sickling activity. Co-incubation of hydroxyurea with deoxygenated blood samples reduced the percentage of sickled cells from 38% to 12 ± 1.6%, whereas the percentage of sickled cells in samples treated with the adduct was 17 ± 1.2%. This indicated loss of anti-sickling activity in the case of the adduct. This study confirmed that hydroxyurea can participate in a Maillard reaction if lactose is used as a diluent. Although an extended study at environmentally feasible temperatures was not carried out in the present investigation, the partial loss of the anti-sickling activity of hydroxyurea was investigated along with the in silico drug-target interactions. The results indicated that the use of lactose in hydroxyurea formulations needs urgent reconsideration and that lactose must be replaced by other diluents that do not form Maillard adducts.

A new highly sensitive low-Z LiF-based OSL phosphor for radiation dosimetry.

A new low-Z lithium fluoride-based optical stimulated luminescent (OSL) phosphor is developed. The phosphor shows good OSL properties, and its sensitivity is comparable with that of the commercial Al2O3:C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 3 s, blue stimulated luminescence (BSL) and green stimulated luminescence (GSL) sensitivities were found to be 0.27 and 4 times, respectively, than that of Al2O3:C (Landauer, Inc.). The BSL decay is fast, and the whole signal decays within 3 s; the GSL decay is relatively slow, and the signal decays in 25 s. The fast decay, good sensitivity, good linearity and its near tissue equivalence (Zeff ∼8.14) will make this phosphor suitable for radiation dosimetry particularly in personnel as well as in medical dosimetry.

Na2SiF6:Cu,P: a new OSL phosphor for the radiation dosimetric applications.

A new Cu,P-doped, sodium fluorosilicate-based optically stimulated luminescence (OSL) phosphor is developed. This phosphor shows good OSL properties, and the sensitivity is comparable with that of the commercial Al(2)O(3):C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 1 s, blue-stimulated luminescence and green-stimulated luminescence sensitivities were found to be 0.76 and 3.8 times, respectively, of Al(2)O(3):C (Landauer, Inc.) with 28 % of post-irradiation fading in 3 days and nil thereafter. The simple preparation procedure, fast decay, very good sensitivity and moderate fading will make this phosphor suitable for radiation dosimetry, using OSL.

Hypolipidemic and antioxidant activity of ethanolic extract of Symplocos racemosa Roxb. in hyperlipidemic rats: an evidence of participation of oxidative stress in hyperlipidemia.

Hypolipidemic and antioxidant activity profiles of ethanolic extracts of Symplocos racemosa (EESR) were studied by triton-WR1339 (acute) and high fat diet induced (chronic) hyperlipidemic rat models. In both the models, a significant increase in total cholesterol (TC), triglycerides (TG), very low density lipoproteins (VLDL), low density lipoproteins (LDL) and decrease in high density lipoproteins (HDL) in serum were observed. EESR (200 and 400 mg/kg) and simvastatin (10 mg/kg) administered orally reduced the elevated serum lipids (TC, TG, VLDL, LDL), restored the decreased HDL and improved the atherogenic index. In high fat diet induced hyperlipidemic model, EESR treatment prevented the increased formation of malondialdehyde (MDA) in liver, restored the depleted liver antioxidants, glutathione, superoxide dismutase, catalase significantly. The increased liver cholesterol, HMG-CoA reductase activity and body weight of hyperlipidemic rats were significantly reduced by EESR treatment. The EESR inhibited HMG-CoA reductase, a rate limiting enzyme in cholesterol biosynthesis, thereby causing hypolipidemic effects. EESR treatment also improved histoarchitecture of hepatocytes in hyperlipidemic rats. Experimental findings demonstrated anti-hyperlipidemic and antioxidant activity of EESR, which may be directly or indirectly related to its antioxidant activity. The hypolipidemic activity of EESR may be due to the presence of flavonoids phenolic compounds, phenolic glycosides and steroids.