A novel polymeric flocculant based on polyacrylamide grafted carboxymethylstarch

Novel functionalized polymeric flocculants based on polyacrylamide grafted carboxymethylstarch (CMS-g-PAM) have been successfully synthesized via conventional method (using ceric ammonium nitrate as free radical initiator, in an inert atmosphere) as well as by using microwave irradiation (‘microwave initiated’ synthesis). Under optimal grafting conditions, 50% grafting has been observed in case of the microwave irradiation based method and 47% grafting has been observed in case of the conventional process. The synthesized graft copolymers have been characterized by elemental analysis, FTIR spectroscopy, intrinsic viscosity measurement, molecular weight determination, ¹³C NMR spectroscopy and scanning electron micrograph (SEM); taking carboxymethylstarch (CMS) as reference. The effects of reaction parameters onto the percentage of grafting have been studied. Further, the applicability of these grafted polymers as flocculants for the treatment of municipal sewage wastewater has also been investigated.     

Defining Efficacy in the Treatment of Overactive Bladder Syndrome

Patients seek treatment for overactive bladder syndrome (OAB) due to poor quality of life, and perceived improvement in quality of life (QOL) from medical therapy is multifactorial. Many feel that efficacy/success of medical therapy for OAB should not be linked to improvements in 1 or 2 endpoints, but instead should be linked to patient expectation and QOL improvement. Ideally, once patient-centered goals are defined, outcomes should be correlated with relief of symptom(s), patient satisfaction, and goal attainment expectations as a result of treatment.Key words: Overactive bladder syndrome, Patient-centered treatment, Medical therapy for OABOveractive bladder syndrome (OAB) as defined by the International Continence Society (ICS) consists of the presence of urinary urgency, with or without urge incontinence, usually with frequency and nocturia.¹ The prevalence rates in both men and women in the United States is estimated at approximately 17%.¹ The total cost of OAB for the year 2000 has been estimated at $12.6 billion.² This cost is made up of diagnostic, treatment, routine care, consequence, and indirect costs from loss of productivity. Due to prevalence and cost of this condition, there are significant resources being utilized to develop treatments that improve patient quality of life (QOL) and reduce the financial burden to society.OAB is a medical problem largely due to its negative impact on daily QOL. The subjective impact of urinary frequency and urgency (with/without urge incontinence) on psychosocial and physical well-being is an important aspect of caring for this group of patients. The severity and degree of bother associated with the symptoms of OAB can directly influence a person’s mobility, degree of social isolation, impairment in work-related activities, disruption of sleep, impairment of domestic and sexual life, and result in depression.³ Patients may also develop extreme coping strategies including self-imposed fluid restrictions, avoidance of social events and travel, and dependence on protective undergarments. OAB not only affects the lives of patients, but also the lives of their caretakers and their QOL. Thus, many patients and their caretakers seek out treatments that will help provide improvement in these aspects of their lives. Unfortunately, relatively few data are available on the effect of current treatments on patient QOL.Most clinical trials evaluating the efficacy of medications and other treatments related to OAB define success as efficacy based on improvements in primary and secondary clinical endpoints. Generally, these clinical endpoints include reduction in incontinence episodes, micturition frequency, urgency measures, and nocturia. The potential problem with this is that clinically significant changes in these parameters compared with placebo may not result in meaningful change in QOL for the patient or the caretaker and may result in discontinuation of medication. Failure to achieve meaningful changes in quality may be related to the fact that a particular symptom is not adequately changed or an adverse event impacts negatively on QOL. A strong argument for this is the poor rate of medication persistence seen in managed care patients with OAB that are significantly lower than reported discontinuation rates from clinical trials.^4–7 Persistence rates for OAB drugs range from 8% to 29% in studies with at least 1 year of follow-up.^4,5,7–9 When comparing extended-release (ER) formulations with immediate-release (IR) formulations, no significant difference was seen in persistence rates after multivariate analysis.⁶ In a study evaluating patient reasoning for OAB medication discontinuation, only one-third of patients cited a single reason for discontinuation, with most citing multiple reasons with a mean of 2.3 reasons.¹⁰ The more common reasons included: 46.2%, “didn’t work as expected”; 21.1%, “side effects”; 17.2%, cost; and 11.2%, “another medication/medical condition required me to stop.” Patient adherence with prescribed therapy is affected by perceived benefit, pill burden, complexity of dosing schedule, memory lapses, and adverse events.¹¹With patients seeking treatment for OAB due to poor QOL and perceived improvement in QOL from medical therapy being multifactorial, it is clear why many believe that efficacy/success of OAB medication probably should not be linked to improvements in 1 or 2 endpoints, but instead should be linked to patient expectation and QOL improvement. Ideally, once patient-centered goals such as the ability to perform certain tasks are defined, outcomes should be correlated with relief of symptom(s), patient satisfaction, and goal attainment expectations as a result of treatment. We need to establish more clear-cut evidence of how a myriad of factors affect treatment response.     

Complexation of phosphatidylcholine lipids with cholesterol

It is postulated that the specific interactions between cholesterol and lipids in biological membranes are crucial in the formation of complexes leading subsequently to membrane domains (so-called rafts). These interactions are studied in molecular dynamics simulations performed on a dipalmitoylphosphatidylcholine (DPPC)-cholesterol bilayer mixture and a dilauroylphosphatidylcholine (DLPC)-cholesterol bilayer mixture, both having a cholesterol concentration of 40 mol %. Complexation of the simulated phospholipids with cholesterol is observed and visualized, exhibiting 2:1 and 1:1 stoichiometries. The most popular complex is found to be 1:1 in the case of DLPC, whereas the DPPC system carries a larger population of 2:1 complexes. This difference in the observed populations of complexes is shown to be a result of differences in packing geometry and phospholipid conformation due to the differing tail length of the two phosphatidylcholine lipids. Furthermore, aggregation of these complexes appears to form hydrogen-bonded networks in the system containing a mixture of cholesterol and DPPC. The CH...O hydrogen bond plays a crucial role in the formation of these complexes as well as the hydrogen bonded aggregates. The aggregation and extension of such a network implies a possible means by which phospholipid:cholesterol domains form.     

The Dietary Supplement Chondroitin-4-Sulfate Exhibits Oncogene-Specific Pro-tumor Effects on BRAF V600E Melanoma Cells

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Oxidative stress increased respiration and generation of reactive oxygen species, resulting in ATP depletion, opening of mitochondrial permeability transition, and programmed cell death

Mitochondria constitute a major source of reactive oxygen species and have been proposed to integrate the cellular responses to stress. In animals, it was shown that mitochondria can trigger apoptosis from diverse stimuli through the opening of MTP, which allows the release of the apoptosis-inducing factor and translocation of cytochrome c into the cytosol. Here, we analyzed the role of the mitochondria in the generation of oxidative burst and induction of programmed cell death in response to brief or continuous oxidative stress in Arabidopsis cells. Oxidative stress increased mitochondrial electron transport, resulting in amplification of H(2)O(2) production, depletion of ATP, and cell death. The increased generation of H(2)O(2) also caused the opening of the MTP and the release of cytochrome c from mitochondria. The release of cytochrome c and cell death were prevented by a serine/cysteine protease inhibitor, Pefablock. However, addition of inhibitor only partially inhibited the H(2)O(2) amplification and the MTP opening, suggesting that protease activation is a necessary step in the cell death pathway after mitochondrial damage.     

Computational structure prediction provides a plausible mechanism for electron transfer by the outer membrane protein Cyc2 from Acidithiobacillus ferrooxidans

Cyc2 is the key protein in the outer membrane of Acidithiobacillus ferrooxidans that mediates electron transfer between extracellular inorganic iron and the intracellular central metabolism. This cytochrome c is specific for iron and interacts with periplasmic proteins to complete a reversible electron transport chain. A structure of Cyc2 has not yet been characterized experimentally. Here we describe a structural model of Cyc2, and associated proteins, to highlight a plausible mechanism for the ferrous iron electron transfer chain. A comparative modeling protocol specific for trans membrane beta barrel (TMBB) proteins in acidophilic conditions (pH ~ 2) was applied to the primary sequence of Cyc2. The proposed structure has three main regimes: Extracellular loops exposed to low‐pH conditions, a TMBB, and an N‐terminal cytochrome‐like region within the periplasmic space. The Cyc2 model was further refined by identifying likely iron and heme docking sites. This represents the first computational model of Cyc2 that accounts for the membrane microenvironment and the acidity in the extracellular matrix. This approach can be used to model other TMBBs which can be critical for chemolithotrophic microbial growth.     

Experimental in vitro mechanical characterization of porcine Glisson's capsule and hepatic veins

Understanding the mechanical properties of human liver is the most critical aspect of numerical modeling for medical applications and impact biomechanics. Many researchers work on identifying mechanical properties of the liver both in vivo and in vitro considering the high liver injury percentage in abdominal trauma and for easy detection of fatal liver diseases such as viral hepatitis, cirrhosis, etc. This study is performed to characterize mechanical properties of individual parts of the liver, namely Glisson's capsule and hepatic veins, as these parts are rarely characterized separately. The long term objective of this study is to develop a realistic liver model by characterizing individual parts and later integrating them. In vitro uniaxial quasi-static tensile tests are done on fresh unfrozen porcine hepatic parts for large deformations at the rate of 0.1mm/s with a Bose Electroforce 3200 biomaterials test instrument. Results show that mean values of small strain and large strain elastic moduli are 8.22 ± 3.42 and 48.15 ± 4.5 MPa for Glisson's capsule (30 samples) and 0.62 ± 0.41 and 2.81 ± 2.23 MPa for veins (20 samples), respectively, and are found to be in good agreement with data in the literature. Finally, a non-linear hyper-elastic constitutive law is proposed for the two separate liver constituents under study.