Electronic properties of neuroleptics: ionization energies of benzodiazepines

Vertical ionization energies (VIEs) of medazepam, nordazepam and their molecular subunits have been calculated using the electron propagator method in the P3/CEP-31G* approximation. Vertical electron affinities (VEAs) have been obtained with a ∆SCF procedure at the DFT-B3LYP/6-31+G* level of theory. Excellent correlations have been achieved between IE_calc and IE_exp, allowing reliable assignment of the ionization processes. Our proposed assignment differs in many instances from that previously reported in the literature. The electronic structure of the frontier Dyson orbitals shows that the IE and EA values of the benzodiazepines can be modulated by substitution at the benzene rings. Hardness values, evaluated as (IE − EA)/2, follow the trend of the experimental singlet transition energies. Medazepam is a less hard (i.e., less stable) compound than nordazepam.     

Comparison Study of Bone Defect Healing Effect of Raw and Processed Pyritum in Rats

To evaluate and compare the effect of raw and processed pyritum on tibial defect healing, 32 male Sprague Dawley rats were randomly divided into four groups. After tibial defect, animals were produced and grouped: sham and control group were orally administrated with distilled water (1 mL/100 g), while treatment groups were given aqueous extracts of raw and processed pyritum (1.5 g/kg) for successive 42 days. Radiographic examination showed that bone defect healing effect of the treatment groups was obviously superior compared to that of the control group. Bone mineral density of whole tibia was increased significantly after treating with pyritum. Inductively coupled plasma-optical emission spectrometry showed that the contents of Ca, P, and Mg in callus significantly increased in the treatment groups comparing with the control. Moreover, serological analysis showed that the concentration of serum phosphorus of the treatment groups significantly increased compared with that of the control group. By in vitro study, we have evaluated the effects of drug-containing serum of raw and processed pyritum on osteoblasts. It was manifested that both the drug-containing sera of raw and processed pyritum significantly increased the mRNA levels of alkaline phosphatase and collagen type I. Protein levels of phosphorylated Smad2/3 also increased. The mRNA levels of osteocalcin and transforming growth factor β (TGF-β) type I and II receptors, as well as the protein levels of TGF-β1 in the processed groups, were higher than those in the control. In summary, both raw and processed pyritum-containing sera exhibited positive effects on osteoblasts, which maybe via the TGF-β1/Smad signaling pathway. Notably, the tibia defect healing effect of pyritum was significantly enhanced after processing.     

Biomedical implications from a morphoelastic continuum model for the simulation of contracture formation in skin grafts that cover excised burns

A continuum hypothesis-based model is developed for the simulation of the (long term) contraction of skin grafts that cover excised burns in order to obtain suggestions regarding the ideal length of splinting therapy and when to start with this therapy such that the therapy is effective optimally. Tissue is modeled as an isotropic, heterogeneous, morphoelastic solid. With respect to the constituents of the tissue, we selected the following constituents as primary model components: fibroblasts, myofibroblasts, collagen molecules, and a generic signaling molecule. Good agreement is demonstrated with respect to the evolution over time of the surface area of unmeshed skin grafts that cover excised burns between outcomes of computer simulations obtained in this study and scar assessment data gathered previously in a clinical study. Based on the simulation results, we suggest that the optimal point in time to start with splinting therapy is directly after placement of the skin graft on its recipient bed. Furthermore, we suggest that it is desirable to continue with splinting therapy until the concentration of the signaling molecules in the grafted area has become negligible such that the formation of contractures can be prevented. We conclude this study with a presentation of some alternative ideas on how to diminish the degree of contracture formation that are not based on a mechanical intervention, and a discussion about how the presented model can be adjusted.     

Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts.

Xeroderma pigmentosum (XP) variant patients are genetically predisposed to sunlight-induced skin cancer. Fibroblasts derived from these patients are extremely sensitive to the mutagenic effect of UV radiation and are abnormally slow in replicating DNA containing UV-induced photoproducts. However, unlike cells from the majority of XP patients, XP variant cells have a normal or nearly normal rate of nucleotide excision repair of such damage. To determine whether their UV hypermutability reflected a slower rate of excision of photoproducts specifically during early S phase when the target gene for mutations, i.e., the hypoxanthine (guanine) phosphoribosyltransferase gene (HPRT), is replicated, we synchronized diploid populations of normal and XP variant fibroblasts, irradiated them in early S phase, and compared the rate of loss of cyclobutane pyrimidine dimers and 6-4 pyrimidine-pyrimidones from DNA during S phase. There was no difference. Both removed 94% of the 6-4 pyrimidine-pyrimidones within 8 h and 40% of the dimers within 11 h. There was also no difference between the two cell lines in the rate of repair during G1 phase. To determine whether the hypermutability resulted from abnormal error-prone replication of DNA containing photoproducts, we determined the spectra of mutations induced in the coding region of the HPRT gene of XP variant cells irradiated in early S and G1 phases and compared with those found in normal cells. The majority of the mutations in both types of cells were base substitutions, but the two types of cells differed significantly from each other in the kinds of substitutions, but the two types differed significantly from each other in the kinds of substitutions observed either in mutants from S phase (P < 0.01) or from G1 phase (P = 0.03). In the variant cells, the substitutions were mainly transversions (58% in S, 73% in G1). In the normal cells irradiated in S, the majority of the substitutions were G.C --> A.T, and most involved CC photoproducts in the transcribed strand. In the variant cells irradiated in S, substitutions involving cytosine in the transcribed strand were G.C --> T.A transversions exclusively. G.C --> A.T transitions made up a much smaller fraction of the substitutions than in normal cells (P < 0.02), and all of them involved photoproducts located in the nontranscribed strand. The data strongly suggest that XP variant cells are much less likely than normal cells to incorporate either dAMP or dGMP opposite the pyrimidines involved in photoproducts. This would account for their significantly higher frequency of mutants and might explain their abnormal delay in replicating a UV-damaged template.     

Alleviation of Liver Dysfunction,Oxidative Stress,and Inflammation Underlines the Protective Effects of Polysaccharides from Cordyceps cicadae on High Sugar/High Fat Diet-Induced Metabolic Syndrome in Rats

This study investigated the protective effects of two polysaccharides (CPA-1 and CPB-2) from Cordyceps cicadae against high fructose/high fat diet (HF/HFD) induced obesity and metabolic disorders in rats. Rats were either fed with normal diet or HF/HFD and treated with CPA-1 and CPB-2 (100 and 300 mg/kg) for 11 weeks. Administration of CPA-1 and CPB-2 significantly and dose dependently reduced body and liver weight, insulin and glucose tolerance, serum insulin and glucose levels. Furthermore, serum and hepatic lipid profiles, liver function enzymes and proinflammatory cytokines (TNF-α, IL-1β and IL-6) were markedly reduced. Additionally, CPA-1 and CPB-2 treatment alleviated hepatic oxidative stress by reducing lipid peroxidation level (MDA) and upregulating glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities as well as ameliorated histological alterations through the reduction of hepatic lipid accumulation. These results suggested that the polysaccharides from C. cicadae showed protective effects against HF/HFD induced metabolic disturbances and may be considered as a dietary supplement for treating obesity.     

Fractionation of the Biopolyols from Lignocellulosic Biomass for the Production of Rigid Foams

The objective of this investigation was to find a simple method for the production of phenolic-rich products and sugar derivatives via separation of liquefied lignocellulosic materials. After liquefaction, the liquefied products were separated by addition of a sufficient amount of water. It was found that those hydrophobic phenolics could be largely separated from aqueous solutions. Preparation of polyurethane foams using biopolyol and isocyanate was studied. Water was used as an environmentally friendly blowing agent. The factors influencing the cell structure of foams such as catalyst, dosage of blowing agent, and mass ratio of biopolyol to PEG were studied. The microstructure of synthesized foams was characterized by SEM.