Preparation and characterization of chitosan films,crosslinked with symmetric aromatic dianhydrides to achieve enhanced thermal properties

This study has developed a new generation of crosslinked chitosan‐based films using symmetric aromatic dianhydrides as crosslinking agents. The formation of the dianhydride‐crosslinked chitosan hydrogel films was confirmed using Fourier transform infrared and solid‐state ¹³C NMR spectral analyses. The films obtained from these derivatives were characterized by their thermal, swelling and hydrophilic properties. The results showed that introducing a cyclic imide moiety into the chitosan matrices played a significant role in enhancing the thermal properties of these chitosan films. It was found that even at high levels of substitution, thermal stability of the studied chitosan derivatives was improved, in spite of a reduction in crystallinity. Heterocyclic imide linkages produced networks that were insoluble in both acidic and alkaline media but allowed swelling in aqueous media. An increase in the hydrophobicity of the chitosan film surfaces was observed after introduction of the cyclic imide moiety. These engineered films produced noteworthy results concerning their thermal and swelling properties. There is a need to further investigate these films for drug delivery and biomaterials applications. © 2014 Society of Chemical Industry     

Using sequence logos and information analysis of Lrp DNA binding sites to investigate discrepanciesbetween natural selection and SELEX

In vitro experiments that characterize DNA-protein interactions by artificial selection, such as SELEX,are often performed with the assumption that the experimental conditions are equivalent to natural ones. To test whether SELEX gives natural results, we compared sequence logos composed from naturally occurring leucine-responsive regulatory protein (Lrp) binding sites with those composed from SELEX-generated binding sites. The sequence logos were significantly different, indicating that the binding conditions are disparate. A likely explanation is that the SELEX experiment selected for a dimeric or trimeric Lrp complex bound to DNA. In contrast, natural sites appear to be bound by a monomer. This discrepancy suggests that in vitro selections do not necessarily give binding site sets comparable with the natural binding sites.     

Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies

Creatine (Cr) and cyclocreatine (cyCr) have been shown to inhibit the growth of a variety of human and murine tumours. The purpose of this study was to evaluate the anti-tumour effect of these molecules in relation to drug accumulation, energy metabolism, tumour water accumulation and toxicity. Nude mice carrying a human colon adenocarcinoma (LS174T) with a creatine kinase (CK) activity of 2.12 units mg(-1) protein were fed Cr (2.5% or 5%) or cyCr (0.025%, 0.1% or 0.5%) for 2 weeks and compared with controls fed standard diet. Cr concentrations of 2.5% and 5% significantly inhibited tumour growth, as did 0.1% and 0.5% cyCr. In vivo 31P magnetic resonance spectroscopy (MRS) after 2 weeks of treatment showed an increase in [phosphocreatine (PCr)+phosphocyclocreatine (PcyCr)]/nucleoside triphosphate (NTP) with increasing concentrations of dietary Cr and cyCr, without changes in absolute NTP contents. The antiproliferative effect of the substrates of CK was not related to energy deficiency but was associated with acidosis. Intratumoral substrate concentrations (measured by 1H-MRS) of 4.8 micromol g(-1) wet weight Cr (mice fed 2.5% Cr) and 6.2 micromol g(-1) cyCr (mice fed 0.1% cyCr) induced a similar decrease in growth rate, indicating that both substrates were equally potent in tumour growth inhibition. The best correlant of growth inhibition was the total Cr or (cyCr+Cr) concentrations in the tissue. In vivo, these agents did not induce excessive water accumulation and had no systemic effects on the mice (weight loss, hypoglycaemia) that may have caused growth inhibition.     

Synthesis, biochemical evaluation, and classical and three-dimensional quantitative structure-activity relationship studies of 7-substituted-1,2,3,4-tetrahydroisoquinolines and their relative affinities toward phenylethanolamine N-methyltransferase and the alpha2-adrenoceptor

7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.     

Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors

PURPOSE: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. METHODS: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. RESULTS: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. CONCLUSION: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.     

Using fluorescence-based human androgen receptor gene assay to analyze the clonality of microdissected dendritic cell tumors

The AGT1 permease is a alpha-glucoside-H+ symporter responsible for the active transport of maltose, trehalose, maltotriose, alpha-methylglucoside, melezitose and sucrose. In wild-type as well as in MAL constitutive strains, alpha-methylglucoside seemed to be the best inducer of transport activity, while trehalose had no inducing effect. Based on the initial rates of transport it seems that the sugar preferentially transported by this permease is trehalose, followed by sucrose.