Functionalized carboxyl nanoparticles enhance mucus dispersion and hydration

Luminal accumulation of viscous, poorly hydrated, and less transportable mucus has been associated with altered mucus rheology and reduced mucociliary clearance. These symptoms are some of the cardinal clinical manifestations found throughout major respiratory diseases as well as gastrointestinal and digestive disorders. Applications of current mucolytics may yield short-term improvements but are continuously challenged by undesirable side-effects. While nanoparticles (NPs) can interact with mucin polymers, whether functionalized NPs can rectify mucus rheology is unknown. Herein, we report that carboxyl-functionalized NPs (24 nm and 120 nm) dramatically reduced mucin gel size and accelerated mucin matrix hydration rate (diffusivity). Our results suggest that carboxyl-functionalized NPs disperse mucin gels possibly by enhancing network hydration. This report highlights the prospective usages of carboxyl-functionalized NPs as a novel mucus dispersant or mucolytic agent in adjusting mucus rheological properties and improving mucociliary transport to relieve clinical symptoms of patients suffering from relevant diseases

Family structure and posttraumatic stress reactions: a longitudinal study using multilevel analyses

<p>Abstract</p> <p>Background</p> <p>There is limited research on the relevance of family structures to the development and maintenance of posttraumatic stress following disasters. We longitudinally studied the effects of marital and parental statuses on posttraumatic stress reactions after the 2004 Southeast Asian tsunami and whether persons in the same households had more shared stress reactions than others.</p> <p>Method</p> <p>The study included a tourist population of 641 Norwegian adult citizens, many of them from families with children. We measured posttraumatic stress symptoms with the Impact of Event Scale-Revised at 6 months and 2 years post-disaster. Analyses included multilevel methods with mixed effects models.</p> <p>Results</p> <p>Results showed that neither marital nor parental status was significantly related to posttraumatic stress. At both assessments, adults living in the same household reported levels of posttraumatic stress that were more similar to one another than adults who were not living together. Between households, disaster experiences were closely related to the variance in posttraumatic stress symptom levels at both assessments. Within households, however, disaster experiences were less related to the variance in symptom level at 2 years than at 6 months.</p> <p>Conclusions</p> <p>These results indicate that adult household members may influence one another's posttraumatic stress reactions as well as their interpretations of the disaster experiences over time. Our findings suggest that multilevel methods may provide important information about family processes after disasters.</p

Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications

A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier

BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases

In-vitro studies of enteric coated diclofenac sodium-carboxymethylcellulose microspheres

10th International Symposium on Microencapsulation -- SEP, 1995 -- AUSTIN, TXWOS: A1996VR22200006PubMed: 8933354Microspheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminium chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit(R)S-100, with aqueous solution concentrations of 10 and 20% (w/v). Encapsulation efficiency, % yield value, particle sizes and in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit(R)S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit(R)S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.Int Microencapsulat So

Design and fabrication of cable bolt for excavation in a fractured rock

Most often in fractured rock masses, large excavations have an unsupported stand-up times less than the minimum time required to support the roof after the excavation. During past few years a wide variety of dowels and bolt types have been developed but most of them failed within a short period of time and the cost were high. Main objective of this research work was to design rock bolts using discarded cables at a low cost. The bolt consists of nearly 1.6m long cable and 16 cm of anchored part. Field data illustrated the amount of load that the bolt can carry as 5 KN. Suggestions were made to improve the design, which will enhance bolt performance. Field tests carried out at Bogala Graphite Lanka Ltd proved that cable bolts are effective in Sri Lankan conditions

Design and fabrication of cable bolt for excavation in a fractured rock

In fractured rock masses, large excavations have an unsupported stand-up times Jess than the minimum time required to support the roof after the excavation. Therefore, the principal objective in the design of a support system is to help the rock mass to support itself. The use of rock bolts is a very flexible supporting method that can be combined with wire mesh, shotcrete and concrete lining. During past years a wide variety of dowels and bolt types were developed but most of them failed within a short period and the cost were high. Advantages of cable strand supports have been well documented and include flexibility, strength, and ease of installation. Main objective of this project is to design rock bolts using discarded wire ropes 01' cables at a low cost. A detailed designing methodology was carried out to fabricate this bolt. The bolt consists of nearly 1.6m long cable and 16 em of anchored part and cable tightening part. Outer diameter of bolt is 33 mm and inner diameter is 12 mm and used cable diameter is Smm. Field data illustrated the amount of load measurements that the bolt can carry is 5 kN, Suggestions were made to improve the design, which will enhance bolt performance. Field tests carried out at Bogala Lanka Graphite Ltd proved that cable bolts are effective in Sri Lankan conditions

New Approaches in Mathematical Biology: Information Theory and Molecular Machines

My research uses classical information theory to study genetic systems. Information theory, founded by Claude Shannon in the 1940&apos;s, has had an enormous impact on communications engineering and computer sciences. Shannon found a way to measure information. We use this measure to precisely characterize the sequence conservation at nucleic-acid binding sites. The resulting methods completely replace the use of &quot;consensus sequences&quot;, and therefore provide better models for molecular biologists. An excess of sequence conservation at bacteriophage T7 promoters and at F plasmid IncD repeats led us to predict the existence of proteins that bind the DNA. In another application of information theory, the wonderful fidelity of telephone communications and compact disk (CD) music can be traced directly to Shannon&apos;s channel capacity theorem. When rederived for molecular biology, this theorem explains the surprising precision of many molecular events. Through connections with the Second Law of T..