Novel waterborne polyurethanes containing long-chain alkanes: their synthesis and application to water repellency

In the fabric finishing field, the water repellents have received increasing interest in recent years and the development of a fluorine-free water repellent has become an attractive prospect. In this study, glyceryl monostearate-modified waterborne polyurethanes (GWPUs) with a branched structure act as water repellents, and were prepared from toluene diisocyanate, trimethylolpropane, hydroxypropyl polydimethylsiloxane, N-methyldiethanolamine, and glyceryl monostearate (GMS). The water repellency and other properties of GWPUs with different GMS content, such as water resistance, hydrophobicity, and air permeability, were studied. The results show that the GMS content for optimum water repellency was 20 wt%, which achieved the highest score (100 points) in a water repellency evaluation. As for the water repellent ability with a GMS content of 20 wt%, the water absorption of a piece of film was reduced to 7.80%, while the water contact angle of terylene coated by the water repellent rose to 148.0°.

In the fabric finishing field, the water repellents have received increasing interest in recent years and the development of a fluorine-free water repellent has become an attractive prospect.     

Silylated oligomeric poly(ether-azomethine)s from monomers containing biphenyl moieties: synthesis and characterization

In this study, four new silicon-containing poly(ether-azomethine)s with linear structures were prepared using original silicon and biphenyl moiety-containing monomers: two diamines and two dialdehydes. The oligomeric natures of the samples were established by GPC analysis, which showed chains containing 3 to 5 repetitive units. The monomers and the oligomeric samples were structurally characterized by NMR and FT-IR spectroscopy. The solubilities of the samples in common organic solvents and their thermal behavior enable improvement of their industrial and technological processability. The optical band gaps of the oligomeric samples were estimated from optical measurements (UV-vis), and their electrical behavior in films was determined using the four-point method. The surface arrangements and morphological characteristics of the films were determined via atomic force microscopy measurements. The roughness, area increase percentage and layer stiffness of the films were also measured using this technique.

In this study, four new silicon-containing poly(ether-azomethine)s with linear structures were prepared using original silicon and biphenyl moiety-containing monomers: two diamines and two dialdehydes.     

Modification of fibrous membrane for organic and pathogenic contaminants removal: from design to application

In this study, a flexible multifunctional fibrous membrane for heterogeneous Fenton-like removal of organic and pathogenic contaminants from wastewater was developed by immobilizing zerovalent iron nanoparticles (Fe-NPs) on an amine/thiol grafted polyester membrane. Full characterization of the resulting polyester membranes allowed validation of successful grafting of amine/thiol (NH₂ or SH) functional groups and immobilization of Fe-NPs (50–150 nm). The Fenton-like functionality of iron immobilized fibrous membranes (PET–Fe, PET–Si–NH₂–Fe, PET–NH₂–Fe, and PET–SH–Fe) in the presence of hydrogen peroxide (H₂O₂) was comparatively studied in the removal of crystal violet dye (50 mg L⁻¹). The effect of pH, amount of iron and H₂O₂ concentration on dye removal was systematically investigated. The highest dye removal yield reached 98.87% in 22 min at a rate constant 0.1919 min⁻¹ (R² = 95.36) for PET–SH–Fe providing 78% toxicity reduction assessed by COD analysis. These membranes could be reused for up to seven repeated cycles. Kinetics and postulated mechanism of colour removal were proposed by examining the above results. In addition, the resultant membranes showed substantial antibacterial activity against pathogenic bacteria (Staphylococcus epidermidis, Escherichia coli) strains studied through disc diffusion-zone inhibitory and optical density analysis. These findings are of great importance because they provide a prospect of textile-based flexible catalysts in heterogeneous Fenton-like systems for environmental and green chemistry applications.

Multifunctional fibrous membrane for heterogeneous Fenton-like removal of organic and pathogenic contaminants from wastewater was developed by immobilizing zerovalent iron nanoparticles (Fe-NPs) on an amine/thiol grafted polyester membrane.     

Functional activated carbon: from synthesis to groundwater fluoride removal

Developing green and functional adsorbents for the removal of inorganic pollutants from industrial wastewater is still a great challenge. Activated carbons (ACs) are promising eco-friendly materials for adsorption applications. This study reports on the preparation and functionalization of AC and its application for fluoride removal from water. Activated carbon was prepared from date stems, and the material was employed as a support for different modifications such as incorporation of Al(OH)₃, in situ dispersion of aluminum particles (Al⁰) and grafting of 3-(aminopropyl)triethoxysilane (APTES). The resulting functional adsorbents were fully characterized by Fourier transform infrared spectroscopy, scanning electronic microscopy, energy dispersive X-ray fluorescence, X-ray diffraction, differential scanning calorimetry and zeta potential analysis. The results evidenced successful surface modifications. All adsorbents had affinity for the removal of fluoride ions (F⁻). The highest F⁻ removal rate was up to 20 mg g⁻¹ for AC-Al(OH)₃. Removal of fluoride ions obeyed Langmuir isotherms and a second-order kinetic model, and reached 99% uptake. The AC-Al(OH)₃ adsorbent was successfully used to treat a groundwater solution contaminated by fluoride ions. These results open an interesting avenue for developing eco-friendly functionalized AC for adsorption applications.

Conversion and surface modification of date stems to obtain a relevant adsorbent to remove fluoride contamination.     

Activity-dependent neuroprotective protein: from gene to drug candidate

Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. The gene encoding ADNP is highly conserved and abundantly expressed in the brain. ADNP contains a homeobox profile and a peptide motif providing neuroprotection against a variety of cytotoxic insults. ADNP mRNA and protein expression responds to brain injury and oscillates as a function of the estrus cycle. The plastic nature of ADNP expression is correlated with brain protection and an association between neuroendocrine regulation and neuroprotection is put forth with ADNP as a focal point. Further understanding of neuroprotective molecules should pave the path to better diagnostics and therapies. In this respect, structure-activity studies have identified a short 8 amino acid peptide in ADNP/NAPVSIPQ (NAP) that provides potent neuroprotection. NAP is currently in clinical development for neuroprotection.     

High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy

Atherosclerosis remains the leading cause of morbidity and mortality in Western countries. Recent evidence has demonstrated that atherosclerosis is not simply a disease of lipid deposition. Inflammation plays a major role in the initiation, progression, and destabilization of atheromas. High-sensitivity C-reactive protein (hs-CRP) is a circulating acute-phase reactant that reflects active systemic inflammation. Large prospective trials have shown hs-CRP to be a strong predictor of future cardiovascular events. Increased hs-CRP concentration is in fact associated with higher cardiovascular events in individuals with and without clinical evidence of atherosclerotic disease. The relative risk associated with hs-CRP is independent of other cardiovascular disease risk factors. Assays for hs-CRP measurement are currently available but must be standardized because patients’ results will be interpreted by using population-based cutpoints. A risk-stratifying algorithm incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been proposed. Further research into the mechanisms and pharmacological treatment of vascular disease will provide novel management strategies in the very near future.     

Susceptibility of Giardia lamblia to aminoglycoside protein synthesis inhibitors: correlation with rRNA structure.

The very limited development of antiparasitic agents targeting protein synthesis stems in part from the belief that parasite and host ribosomes are sufficiently similar to preclude selective toxicity. However, recent studies have revealed that Giardia lamblia rRNA has an unusual size and sequence; consequently, this organism and its homogeneous rRNA provide a useful model for the development of protein synthesis inhibitors with antiparasitic activity. In this study, I determined the sequence and secondary structure of the 3' end of the small-subunit RNA, the target for aminoglycoside inhibitory activity. The primary structure of these 140 nucleotides includes two blocks of sequence highly conserved among other organisms; the remaining sequence, although not conserved, can be folded into a secondary structure common to all rRNAs. The presence of U-1495 within one of the conserved blocks predicts hygromycin susceptibility. Also, a specific base pair (C-1409.G-1491) implicated in paromomycin susceptibility is present; whereas all procaryotes have this base pair, it is absent in many eucaryotes (including mammals). Conversely, kanamycin and apramycin resistance can be predicted from substitution of A-1408 with G. A growth inhibition assay was used to test the susceptibility of G. lamblia to a variety of aminoglycosides. After 48 h, 8 of 11 aminoglycosides tested failed to inhibit growth at a concentration of 200 micrograms/ml. Paromomycin and hygromycin, however, inhibited growth of three strains tested by 50% at 50 to 60 micrograms/ml and by close to 90% at 120 micrograms/ml. These results correlate well with the sequence and secondary-structure analyses. Paromomycin may be clinically useful when the toxicity of standard antigiardial drugs is of concern.     

Molecular mechanisms of endothelial dysfunction: from nitric oxide synthesis to ADMA inhibition

Endothelial dysfunction symbolizes several pathological conditions, including altered anticoagulant and anti-inflammatory properties of the endothelium, impaired modulation of vascular growth, and dysregulation of vascular remodeling. Nevertheless, this term has been used commonly to refer to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide bioactivity. The clinical and scientific relevance of nitric oxide synthesis and bioavailability in endothelial dysfunction is based on the fact that it is a common factor in the pathogenesis of cardiovascular diseases. These alterations have been demonstrated in both animal models and humans, in the scope of dangerous pathological conditions such as cigarette smoking, hypertension, hypercholesterolemia, aging, diabetes, and heart failure. A decline in nitric oxide bioavailability may be caused by decreased expression of the endothelial nitric oxide synthase, a reduction of substrate or cofactors for this enzyme, alterations of cellular signaling, enzyme inhibition by asymmetric dimethyl arginine, and, finally, accelerated nitric oxide degradation by reactive oxygen species. The knowledge of the processes related to these alterations becomes of remarkable importance for understanding the generation of innovative and effective therapeutic strategies for cardiovascular diseases.     

Neuropsychiatric adverse events after switching from an antiretroviral regimen containing efavirenz without tenofovir to an efavirenz regimen containing tenofovir: a report of nine cases

The combination of tenofovir (TDF) and efavirenz (EFV) has not been associated with any pharmakokinetic interaction or with enhancement of neuropsychiatric disturbances. We report nine cases of neuropsychiatric intolerance occurring early after a switch from an antiretroviral regimen without TDF to an EFV and TDF-containing regimen. Nine HIV-1-infected patients were treated with an EFV-containing regimen for a median duration of 31 months without any EFV-related central nervous system (CNS) effects. They were switched to an EFV-TDF-containing regimen because of lipodystrophy (n=2) and/or the wish to simplify to a once-daily regimen (n=9). Moderate to severe neuropsychiatric events occurred immediately (<48 hours) after TDF initiation in five patients and 2 weeks to 24 months after the switch in the remaining four patients. Treatment modifications occurred in six patients (switch to EFV-nevirapine [n=3], TDF-zidovudine [n=2] or treatment discontinuation [n=1]), leading to a marked improvement of CNS intolerance. Treatment remained unchanged in three patients; two patients experienced chronic persistent sleeping disorders and one patient underwent a spontaneous improvement of symptoms within 2 weeks. EFV plasma concentrations, which were available in two patients before the switch and in four patients after the switch, remained in the therapeutic range. Although the exact mechanism of these symptoms remains hypothetical, neuropsychiatric disorders could be either a consequence of an unexplained interaction between EFV and TDF or an infrequent TDF-related side effect. The incidence of these side effects needs to be evaluated in large databases or pharmacokinetic studies.     

Utilization for protein synthesis of 2-ketoisocaproate relative to utilization of leucine, as estimated from exhalation of labelled CO2

1. We have previously shown that the ratio (RWBP) of incorporation of label from 2-ketoisocaproate (KIC) into the leucine of whole-body protein to the simultaneous incorporation of label from leucine itself into protein is a measure of the nutritional efficiency of KIC as a substitute for leucine. 2. In order to determine whether RWBP can be estimated indirectly from measurement of labelled CO2 excretion, rats were injected orally or intravenously with [4,5-3H]leucine and either [1-14C]leucine or [1-14C]KIC. Expired CO2 was collected for 6 h. 3. The results show that 9-14% of KIC underwent first-pass oxidation after oral administration. When isotopes were given intravenously, the mean rate of excretion of 14CO2 from KIC, after 20 min, remained 1.8 times the mean rate of excretion of 14CO2 from leucine. 4. Mean RWBP, measured in whole-body protein in rats given isotopes orally or intravenously along with small or large doses of carriers, was the same as mean RWBP estimated from mean cumulative CO2 excretion. 5. We conclude (1) that nutritional efficiency of KIC relative to leucine can be estimated from measurement of labelled CO2 excretion, and (2) that the relative inefficiency of KIC as a substitute for leucine in the rat is attributable to first-pass oxidation of 9-14% (when given orally) and 80% greater susceptibility to systemic oxidation than leucine.     

Iron catalyzed C–C dehydrogenative coupling reaction: synthesis of arylquinones from quinones/hydroquinones

An atom-economical approach for the synthesis of arylquinones was achieved successfully via direct oxidative C–C dehydrogenative coupling reaction of quinones/hydroquinones with electron-rich arenes using an inexpensive Fe–I₂–(NH₄)₂S₂O₈ system. The efficiency of this catalytic approach was established with a broad scope of substrates involving quinones and hydroquinones to give high yields (60–89%) of several arylated quinones. The present protocol is simple, practical, and shows good functional group tolerance.

The synthesis of arylquinones was achieved via direct oxidative C–H/C–H cross-coupling of quinones/hydroquinones with electron-rich arenes using Fe–I₂–(NH₄)₂S₂O₈ system involving quinones/hydroquinones to give high yields (60–89%) of arylquinones.     

Potential of macrolide antibiotics to inhibit protein synthesis of Pseudomonas aeruginosa: suppression of virulence factors and stress response

Recently we have reported that sub-minimum inhibitory concentrations (MICs) of macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin, induce loss of viability of Pseudomonas aeruginosa with longer incubation periods. In the present study we examined the effects of sub-MICs of macrolide antibiotics on protein synthesis and the expression of heat shock proteins (Gro-EL) in P. aeruginosa and the association of these factors with the viability of P. aeruginosa. In seven strains of P. aeruginosa clinical isolates, inhibition of protein synthesis was generally observed in bacteria grown on agar with sub-MIC azithromycin (8 μg/ml) at 24 h, and this was followed by loss of viability after an additional 24-h incubation. The inhibition of protein synthesis was shown in bacteria treated with sub-MICs of erythromycin and clarithromycin, but not with sub-MICs of other antibiotics examined (josamycin, tobramycin, ofloxacin, clindamycin, and ceftazidime) even at relatively high sub-MICs. In the heat shock condition (45°C), strong expression of the heat shock protein Gro-EL was induced in bacteria grown on antibiotic-free medium, whereas there was a delay of such a response in bacteria exposed to 4 μg/ml of azithromycin. Reflecting these results, an abrupt reduction of viability in azithromycin-treated bacteria was observed within 3 h in the heat shock condition. Western blot analysis, using specific antibody for Gro-EL, demonstrated that erythromycin, clarithromycin, and azithromycin, at concentrations of 0.5–2 μg/ml, inhibited the expression of lower-molecular weight Gro-EL bands in the constitutive state. These results indicated that macrolides, at concentrations far below the MICs, suppressed protein synthesis in P. aeruginosa, an effect which may be associated with the inhibition of P. aeruginosa virulence and its loss of viability with longer incubation. Moreover, it is likely that the macrolides may sensitize bacteria to stresses, as these antibiotics induced alterations in a major stress protein, Gro-EL, in constitutive and inducible states. Received: September 13, 1999 / Accepted: December 7, 1999     

Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.     

Designing specific protein kinase inhibitors: insights from computer simulations and comparative sequence/structure analysis

Protein kinases are important targets for designing therapeutic drugs. We describe here a computational approach to extend the usefulness of a single protein-inhibitor structure in aiding the design of protein kinase inhibitors. This approach is based on using sensitivity analysis to identify the most significant functional groups of a lead compound in accounting for binding affinity and on using comparative sequence/structure analysis to examine whether these functional groups would present specificity. A sensitivity analysis study is similar to genetic or chemical modification experiments in which specific features of a lead compound are modified to examine whether they affect properties such as binding affinity. In this study, the binding affinity was estimated by using an implicit-solvent model in which the electrostatic contributions were obtained by solving the Poisson equation, and the hydrophobic effects were accounted for by using surface-area-dependent terms. The comparative sequence/structure analysis involves the study of the amino acid distributions of a large number of protein kinases (384 in this study) near the ligand-binding sites. This analysis provides useful guiding principles for designing specific inhibitors targeted towards a particular kinase. Here, we illustrate the utility of these computational approaches by applying them to identify the determinants of the recognition between the protein kinase A and two of its inhibitors. One inhibitor, balanol, binds to the ATP-binding pocket. The other, protein kinase inhibitor, binds to the substrate-binding site. These analyses have helped to construct pharmacophore models for mining new drug leads from small-molecule libraries and for suggesting how a lead compound or a peptide inhibitor may be modified to generate selective inhibitors.     

Putting genome analysis to good use: lessons from C-reactive protein and cardiovascular disease

New methods of studying the human genome offer novel ways to examine the relationship between biomarkers and common, chronic human diseases. As an example, we will review a large genomics study (Elliott et al, JAMA 2009; 302:37-48) that concluded that C-reactive protein (CRP) is likely not a cause of coronary heart disease, although it is a marker for it.     

Fluorescent delivery vehicle containing cobalt oxide–umbelliferone nanoconjugate: DNA/protein interaction studies and anticancer activity on MF7 cancer cell line

Fluorescent labeling is limited to certain molecules and alters biomolecule functionality. A new class of nanomaterial with anticancer activity and fluorescence properties has been designed and prepared. This nanotherapeutic conjugate of natural molecules has a selective binding site in cancer cell lines. Natural drug umbelliferone was taken with cobalt metal ions in a one pot assembly in the presence of tannic acid which yields new fluorescent nanoparticles of umbelliferone cobalt oxide nanoconjugate. Umbelliferone has high fluorescent properties and also has coordination ability to bind with central metal ions. The nanoconjugate was synthesized and characterized by using TEM, EDX analysis, SEM, XRD, and FTIR spectroscopy. TEM shows that the average size of the particles formed with umbelliferone is ∼20 nm. The solubility of the drug nanoparticles in water showed compatibility with cancer cells and provided a favorable environment to investigate the mechanism of action on the MCF-7 cell line. The nanoconjugate is microcrystalline in nature and gives a clear suspension in water. The nanocobalt conjugate was loaded on TiO₂ nanoparticles by ultrasonication, and the solution was digested overnight. The conjugate of the drug with a TiO₂ drug carrier was stable in solution and maintained the nanostructure ∼34.6 nm. A comparative study with nano-vehicle TiO₂ and the nanoconjugate was performed. TiO₂ was used to compare the anti-cancer activity of the nanoconjugate at low dose in vitro. It was observed that the nanoconjugate with TiO₂ is capable of reaching the specific target like the TiO₂ nanoparticle and enhance the chemotherapeutic impact. Hence, the nanoconjugate can also be used like nano-TiO₂, as the drug and carrier. The ct-DNA and HSA protein binding studies were done and validated by docking studies.

Model of drug-nanoconjugate with DNA and HSA.