Effect of end-groups on sulfobetaine homopolymers with the tunable upper critical solution temperature (UCST)

One-step syntheses of well-defined Poly(3-((2-(Methacryloyloxy) ethyl) (dimethyl) ammonio)-1-propanesulfonate) (PDMAPS) with a carboxylic acid end-functional reversible addition-fragmentation chain transfer (RAFT) agent and further end-group modification were described. The upper critical solution temperature (UCST) of homo-zwitterions can be precisely adjusted by the surrounding pH due to the presence of a carboxyl end-group. Meanwhile, after esterification of the carboxylic acid group by methyl, ethyl, hexyl, phenethyl alcohol, UCST of all resulted PDMAPS with ester terminated groups showed more significant increases. Dynamic light scattering (DLS), Zeta-potential and small-angle X-ray scattering (SAXS) results demonstrated that the ionization/protonation from the carboxylic end-group and hydrophobicity of ester groups contribute significantly to the tunability. This end-group modification technique provides an easy and economical way of synthesizing temperature-responsive homo-polyzwitterions with precise and controllable temperature range owing to the designability of RAFT polymerization, where the products are suitable for biomedical and environmental engineering applications

Barium Promotes Anchorage-Independent Growth and Invasion of Human HaCaT Keratinocytes via Activation of c-SRC Kinase

Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl2) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5–50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5–5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

Impact of delay in early swallow screening on pneumonia, length of stay in hospital, disability and mortality in acute stroke patients

Background/Objectives: Early swallow screening, within 4 h of admission, is required for all acute stroke patients to commence nutritional support, as recommended. We evaluated the impact of delay in early swallow screening on outcomes in patients admitted with acute stroke. Subjects/Methods: Prospective cohort study of 1656 men (mean ± SD age = 73.1y ± 13.2) and 1653 women (79.3y ± 13.0) admitted with stroke to hyperacute stroke units (HASUs) in Surrey. Logistic regression was used to assess the risk (adjusted for age, stroke severity and co-morbidities) of delay in swallow screening on pneumonia, length of stay (LOS) > 3 weeks in HASU or hospital, moderately severe to severe disability on discharge (modified Rankin scale score = 4–5) and mortality during admission. Results: Compared with those who received swallow screening within 4 h of admission, a delay between 4 and 72 h was associated with greater risks of pneumonia: OR = 1.4 (95%CI:1.1–1.9, P = 0.022), moderately severe to severe disability on discharge: OR = 1.4 (1.1–1.7, P = 0.007) and a delay beyond 72 h was associated with even greater risks of pneumonia: OR = 2.3 (1.4–3.6, P < 0.001), prolonged LOS in HASU: OR = 1.7 (1.0–3.0, P = 0.047, median LOS = 6.2 vs. 14.7 days) and hospital: OR = 2.1-fold (1.3–3.4, P = 0.007, median LOS = 6.8 vs. 14.9 days), moderately severe to severe disability on discharge: OR = 2.5 (1.7–3.7, P < 0.001) and mortality: OR = 3.8 (2.5–5.6, P < 0.001). These risks persisted after excluding 103 patients who died within 72 h. Conclusions: Delay in early screening for swallow capacity in acute stroke patients is detrimental to outcomes, possibly due to delaying nutritional provision or through inappropriate feeding leading to aspiration. Routine early screening needs greater attention in HASUs

Synthesis of star-shaped polyzwitterions with adjustable UCST and fast responsiveness by a facile RAFT polymerization

Dual thermo- and pH-responsive star polymers with tunable upper critical solution temperatures (UCST) were synthesized by an “arm-first” RAFT polymerization approach. Crosslinking took place in a single step involving polymerization of 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) mediated by a macroRAFT agent containing carboxylic end-group and in the presence of crosslinker N,N-methylenebis(acrylamide) (MBA). Varied-temperature turbidity analysis, dynamic light scattering (DLS) and rheology analysis revealed that the star-shaped PDMAPS had a smaller hydrodynamic volume while retaining fast response properties, compared with linearly-shaped PDMAPS. Meanwhile, zeta-potential was used to determine that the range of UCST regulated by pH was greatly expanded and proportional to the number of end-groups that could be generally manipulated through RAFT polymerization. By changing the pH values from 3 to 10, the adjustable UCST range of the star polymer solution can reach over 36 °C. These results demonstrate that the topological structure and end-group effect are able to manipulate the phase transition behavior of polyzwitterions. These materials offer great potential as additives or drug delivery vehicles in biomedical applications

The crosslinking mechanism in gamma irradiation of polyarylsulfone: Evidence for Y-links

Measurements of molecular weights, soluble fractions and examination of NMR spectra of bisphenol-A polysulfone, after gamma irradiation in vacuum at 150 degrees C were used to elucidate the mechanism of crosslinking. Excellent agreement was obtained between G(S) and G(X) determined from measurements above and below the gel dose when a Y-linking mechanism was assumed, whereas poor agreement was obtained when an H-link mechanism was assumed, which is the mechanism normally believed to be responsible for crosslinking. New resonances were observed in the C-13 NMX spectra of the irradiated polymer which were consistent with the formation of Y-links involving phenylene units in the backbone chain. (C) 1998 John Wiley & Sons, Ltd