Evaluation of subclinical left ventricular systolic dysfunction using two-dimensional speckle-tracking echocardiography in patients with Child-Pugh A and B cirrhosis: A case-control study.

BACKGROUND: Although studies have proven that liver cirrhosis affects cardiac hemodynamics by means of circulatory overload, they present with definite cardiac functional alteration mostly with end-stage disease. There is limited data on relationship between progression of cirrhosis, cardiac mechanics and sub-clinical dysfunction. This study was done to assess ventricular myocardial mechanics using speckle tracking and deformation imaging among Child-Turcotte-Pugh (CTP) classification A and B cirrhosis. METHOD: Seventy patients with cirrhosis of Child-Pugh A/B class and sixty-two healthy subjects were prospectively evaluated by standard conventional echocardiography and deformation imaging with rotational echocardiography. Clinical stage of liver cirrhosis was assessed by model for end-stage liver disease (MELD) scores and CTP classification. RESULTS: Mean ages of patients with cirrhosis and controls were 55.64±14 years and 52.24±12 years, respectively. Though left ventricular (LV) dimensions (end diastolic dimension: 47.27±4.6 mm vs. 45.03±3.8 mm, p = 0.003; end systolic dimension: 30.33±4.9 mm vs. 28.40±2.91 mm, p = 0.006) and volumes (end diastolic volume: 82.08±22.53 mL vs. 68.18±15.75 mL, p = 0.001; end systolic volume: 28.60±8.42 mL vs. 22.18±7.48 mL, p = 0.001) were significantly higher in patients with cirrhosis, mean ejection fraction (EF) by Simpsons method was higher among controls (65.83±5.79% vs. 68.35±5.79%, p = 0.009). Left atrial volume was higher in cirrhosis group indicating presence of diastolic dysfunction (41.24±14.10 mL vs. 26.08±6.4 mL, p = 0.001). Global longitudinal strain as assessed by speckle tracking echocardiography did not show statistical significant difference between two groups (-22.35±4.08% vs. -21.80±2.54%, p = 0.348). Median value of torsion parameters in patients with cirrhosis did not differ compared to controls (torsion in degrees: 2.46 vs. 2.79, p = 0.268). CONCLUSION: Patients with Child-Pugh A and B stages of cirrhosis present with preserved longitudinal strain, normal torsion but with subtle diastolic dysfunction. Higher MELD score may correlate with increased longitudinal strain possibly due to hyperdynamic state.

Transfacetal Screw Fixation for Subaxial Cervical Spine.

Background and Introduction: In the modern era of spine surgery for subaxial cervical spine, transfacetal screw fixation has evolved enormously. Transfacetal screw fixation for subaxial cervical spine is a biomechanically effective technique. In this fixation, four cortical surfaces of the facets are purchased by the transfacetal screws. Objectives: In this video, we demonstrated the surgical technique of posterior transfacetal screw fixation. Surgical Technique: Transfacetal screw fixation of subaxial cervical spine was done along with posterior decompression. The entry point of transfacetal screw was defined as 1 mm caudal to mid-point of lateral mass, and screws were directed perpendicular to facet joint in the sagittal plane and straight in the coronal plane. Bone chips were placed over decorticated lateral mass after decompression. Result: Patient had uneventful recovery and maintained good status at follow up. Conclusion: In subaxial cervical spine, transfacetal screw fixation is a biomechanically effective, rigid, and an inexpensive technique to obtain immediate rigid fixation.

Iontophoretic permeation of lisinopril at different current densities and drug concentrations.

PURPOSE: The purpose of the present work was to assess iontophoretic permeation of Lisinopril at different current densities and concentrations for development of patient-controlled active transdermal system. METHODS: In vitro iontophoretic transdermal delivery of Lisinopril across the pigskin was investigated at three different drug concentrations and three different current densities (0.25- 0.75 mA/cm2) in the donor cell of the diffusion apparatus, using cathodal iontophoresis along with the passive controls. RESULTS: For passive permeation, the steady state flux significantly increased with the increasing of donor drug concentration. At all concentration levels, iontophoresis considerably increased the permeation rate compared to passive controls. Iontophoretic transport of Lisinopril was to be found increase with current densities. Flux enhancement was highest at the lowest drug load and lowest at the highest drug load. CONCLUSION: The obtained results indicate that permeation rate of Lisinopril across the pigskin can be considerably enhanced, controlled or optimized by the use of Iontophoresis technique.

Rate enhancement of an interfacial biochemical reaction through localization of substrate and enzyme by an adaptor domain.

This paper describes a model system to characterize the rate enhancement that stems from localization of an enzyme with its substrate. The approach is based on a self-assembled monolayer that presents a substrate for the serine esterase cutinase along with a peptide ligand for an SH2 adaptor domain. The monolayer is treated with a fusion protein of cutinase and the SH2 domain, and the rate for the interfacial reaction is monitored using cyclic voltammetry. The rate is approximately 30-fold greater for monolayers that present the ligand for the SH2 domain than for those that omit the ligand. The rate enhancement is due to the interaction of the adaptor domain with the immobilized ligand. Further, the rate enhancement increases with the densities of both the ligand and the substrate. This example provides a well-defined model system for quantitatively assessing the magnitude of rate enhancement that is possible with colocalization of an enzyme with its substrate and may be particularly significant for understanding the signaling events that rely on enzyme localization at the cell membrane.

Determination of kinetic parameters for interfacial enzymatic reactions on self-assembled monolayers.

This paper reports a method to characterize the kinetic constants for the action of enzymes on immobilized substrates. This example uses cutinase, a serine esterase that hydrolyzes 4-hydroxyphenyl valerate moieties that are immobilized on a self-assembled monolayer of alkanethiolates on gold. The product of the enzyme reaction is a hydroquinone, which is redox active and therefore permits the use of cyclic voltammetry to monitor the extent of reaction in situ. A kinetic model based on the Michaelis-Menten formalism is used to analyze the dependence of initial rates of reaction on both the substrate density and the enzyme concentration. The resulting value of k(cat)/K(M) for the interfacial reaction is comparable to that for a homogeneous phase reaction with a substrate of similar structure. This strategy of using monolayers presenting substrates for the enzyme and cyclic voltammetry to measure reaction rates provides quantitative and real-time information on reaction rates and permits a level of analysis of interfacial enzyme reactions that to date has been difficult to realize.

Soft nanotechnology with soft nanoparticles.

The last decade of research in the physical sciences has seen a dramatic increase in the study of nanoscale materials. Today, "nanoscience" has emerged as a multidisciplinary effort, wherein obtaining a fundamental understanding of the optical, electrical, magnetic, and mechanical properties of nanostructures promises to deliver the next generation of functional materials for a wide range of applications. While this range of efforts is extremely broad, much of the work has focused on "hard" materials, such as Buckyballs, carbon nanotubes, metals, semiconductors, and organic or inorganic dielectrics. Meanwhile, the soft materials of current interest typically include conducting or emissive polymers for "plastic electronics" applications. Despite the continued interest in these established areas of nanoscience, new classes of soft nanomaterials are being developed from more traditional polymeric constructs. Specifically, nanostructured hydrogels are emerging as a promising group of materials for multiple biotechnology applications as the need for advanced materials in the post-genomic era grows. This review will present some of the recent advances in the marriage between water-swellable networks and nanoscience.

Bioresponsive hydrogel microlenses.

We report investigations of bioresponsive hydrogel microlenses as a new protein detection technology. Stimuli-responsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) microgels have been synthesized via free-radical precipitation polymerization. These hydrogel microparticles were then functionalized with biotin via EDC coupling. Hydrogel microlenses were prepared from the particles via Coulombic assembly onto a silane-modified glass substrate. Arrays containing both pNIPAm-co-AAc microgels (as an internal control) and biotinylated pNIPAm-co-AAc microgels were then used to detect multivalent binding of both avidin and polyclonal anti-biotin. Protein binding was determined by monitoring the optical properties of the microlenses using a brightfield optical microscopy technique. The microlens method is shown to be very specific for the target protein, with no detectable interference from nonspecific protein binding. Finally, the reversibility of the hydrogel microlens assay has been studied in the case of anti-biotin to determine the potential application of the microlens assay technology in a displacement-type assay. These results suggest that the microlens method may be an appropriate one for label-free detection of proteins or small molecules via displacement of tethered protein--ligand pairs.

Hollow thermoresponsive microgels.

Thermoresponsive poly(N-isopropyl acrylamide) (pNIPAm) microgels possessing a hollow structure have been synthesized from core-shell nanoparticles upon oxidation of the particle core, followed by removal of the produced polymer segments by centrifugation. N,N'-(1,2-dihydroxyethylene)bisacrylamide (DHEA) is used as a cross-linker for preparing the degradable core, whereas N,N'-methylenebis(acrylamide) (BIS) is used as a cross-linker to add a nondegradable pNIPAm shell. Addition of NaIO(4) to a suspension of these particles in water leads to controlled degradation of the particle core by cleavage of the 1,2-glycol bond in DHEA. Fluorescence spectroscopy, UV/Vis spectroscopy, and photon correlation spectroscopy are used to characterize the hollow particles produced.

Folate-mediated cell targeting and cytotoxicity using thermoresponsive microgels.

We describe the design of fluorescent, thermoresponsive microgels surface-functionalized with folic acid. Incubation of these particles with KB cells grown in folate-free medium results in efficient endocytosis of the particles via a receptor-mediated pathway. Laser scanning confocal microscopy and flow cytometry show efficient uptake of folate-modified particles over cationic control particles. Staining of the cells with Lysotracker red, followed by confocal imaging, shows anticorrelation between the particle and endosome fluorescence, which is taken as evidence of particle escape from the endosomes to the cytosol. Finally, the strong dependence of particle swelling on temperature was used to induce particle collapse and aggregation following uptake, which causes significant cytotoxicity. Thus, we have developed polymeric nanoparticles that may display antitumor activity, as they effectively target cancer cells and undergo endosomal escape to the cytosol, and they can then be triggered to cause cell death.

Antimicrobial activity of the roots of cocculus hirsutus.

Cocculus hirsutus Linn was studied for antimicrobial activity against Staphylococcus aureus, Echerchia coli, Pseudomonas aeruginosa and Salmonella typhi using agar disc-diffusion method. Petroleum ether extract, Ethanolic extract and Crude alkaloidal fraction were screened for the activity in various concentrations and zone of inhibitions were recorded. Results suggest that the Ethanolic extract and Crude alkaloidal fraction have significant antimicrobial activity against test microorganisms and the activity is found to be concentration dependent. Present findings justify the claimed uses of Cocculus hirsutus in the indigenous systems of medicine to treat various infectious diseases.