A nudge over the relaxation plateau: effect of pH, particle concentration, and medium viscosity on the AC induction heating efficiency of biocompatible chitosan-coated Fe3O4nanoparticles.

The effects of pH, MNP concentration, and medium viscosity on the magnetic fluid hyperthermia (MFH) properties of chitosan-coated superparamagnetic Fe3O4nanoparticles (MNPs) are probed here. Due to the protonation of the amide groups, the MNPs are colloidally stable at lower pH (∼2), but form aggregates at higher pH (∼8). The increased aggregate size at higher pH causes the Brownian relaxation time (τB) to increase, leading to a decrease in specific absorption rate (SAR). For colloidal conditions ensuring Brownian-dominated relaxation dynamics, an increase in MNP concentrations or medium viscosity is found to increase theτB. SAR decreases with increasing MNP concentration, whereas it exhibits a non-monotonic variation with increasing medium viscosity. Dynamic hysteresis loop-based calculations are found to be in agreement with the experimental results. The findings provide a greater understanding of the variation of SAR with the colloidal properties and show the importance of relaxation dynamics on MFH efficiency, where variations in the frequency-relaxation time product across the relaxation plateau cause significant variations in SAR. Further, thein vitrocytotoxicity studies show good bio-compatibility of the chitosan-coated Fe3O4MNPs. Higher SAR at acidic pH for bio-medically acceptable field parameters makes the bio-compatible chitosan-coated Fe3O4MNPs suitable for MFH applications.

Inter-droplet force between magnetically polarizable Pickering oil-in-water nanoemulsions stabilized with γ-Al2O3 nanoparticles: Role of electrostatic and electric dipolar interactions.

HYPOTHESIS: The presence of nanoparticles at oil-water interface influences the interaction forces between Pickering emulsions. When charged nanoparticles are at the oil-water interface of an electrostatically stabilized emulsion, in addition to the screened Coulombic interaction, electric dipolar force also influences the total inter-droplet force profiles. An in-depth understanding of the effects of such electric dipolar forces is essential for designing colloidally stable Pickering nanoemulsions for various applications. EXPERIMENTS: Inter-droplet forces between γ-Al2O3 nanoparticle stabilized oil-in-water nanoemulsion, containing superparamagnetic nanoparticles (magnetically polarizable) in the oil phase, are measured using the magnetic-chaining technique at different pH and salt concentrations. The role of mono-, di- and tri-valent salts on the inter-droplet force profiles are assessed. FINDINGS: Force measurement studies reveal a lowering of inter-droplet spacing, within the linear chains, for higher salt concentrations due to an increased screening. Strong interfacial attachment of the charged nanoparticles results in the formation of an asymmetric charge cloud leading to an electric dipolar interaction. Incorporating the contributions of electric dipolar and screened Coulombic interactions, the theoretically estimated total repulsive force magnitudes are in good agreement with the experimental data. The obtained results offer better insights into the nature of colloidal force between charged particle stabilized nanoemulsions.

Infrared thermal imaging based study of localized cold stress induced thermoregulation in lower limbs: The role of age on the inversion time.

Thermoregulatory control of human body temperature is of paramount importance for normal bodily functions. Exposure of the upper and lower limbs to localized cold stress can cause cold-induced injuries and often lower limbs are more susceptible to damages from cold-induced injuries. In this study, we use infrared thermal imaging to probe localized cold stress induced cutaneous vasoconstriction of lower limbs in 33 healthy subjects. The cold stress is actuated by applying ice to the plantar surfaces of the lower limbs for 180 s and after removal of the cold stress, infrared thermography is utilized to non-invasively monitor the time-dependent variations in vein pixel temperatures on the dorsal surfaces of the stimulated and non-stimulated feet. It is observed that the vein pixel temperature of the stimulated foot showed a non-monotonic variation with time, consisting of an initial decrease and the presence of an inversion time, beyond which temperature is regained. The initial decrease in vein pixel temperature of the stimulated foot is attributed to the reduced blood flow caused by the cold stress induced severe vasoconstriction. Beyond the inversion time, the vein pixel temperature is found to increase due to rewarming of the surrounding skin. Experimental findings indicate that the inversion time linearly increased with the age of the subject, indicating a reduced thermoregulatory efficiency for the aged subjects. This study provides a thermal imaging-based insight into the skin temperature re-distribution during the early stages of blood perfusion in lower limbs, after an exposure to a localized acute cold stress. Statistical analyses reveal that subject height, weight, body-mass index and gender do not influence the inversion time significantly. The experimental findings are important towards rapid evaluation of personnel fitness for deployment in extreme cold environment, treatment of cold-induced injuries and probing of thermoregulatory impairments.

Enhanced magnetic heating efficiency at acidic pH for magnetic nanoemulsions stabilized with a weak polyelectrolyte.

HYPOTHESIS: Magnetic fluid hyperthermia has attracted considerable attention for cancer therapeutics. Magnetic nanoemulsions are potential candidates for multi-modal hyperthermia due to the possibility of volumetric loading with suitable chemo/photo-therapy agents. Often, the nanocarriers are stabilized using organic molecules that behave differently under varying pH and hence, an understanding of their interfacial behaviour is important for practical applications. EXPERIMENTS: We probe the magnetic heating efficiency of poly acrylic acid (PAA) stabilized oil-in-water magnetic nanoemulsions, as a function of pH, where the conformational changes of the PAA molecules are studied using dynamic light scattering and inter-droplet force measurements. FINDINGS: A ~50% enhanced heating efficiency is observed when solution pH is reduced from ~9 to 3, which is attributed to the coil-to-globule conformational changes of the PAA molecules. The increased ionization of the carboxylic acid groups, at higher pH, leads to reduced hydrophobicity that results in an increase in the interfacial thermal resistance causing a lower magneto-thermal heating efficiency at higher pH. The proposed interfacial heat transfer hypothesis is experimentally verified using thermal imaging, where a lower rate of heat transfer is obtained at higher pH. The observed enhanced hyperthermia efficiency at low pH is beneficial for designing efficient pH-responsive nano-carriers for multi-modal hyperthermia.

Asymmetric split H-shape nanoantennas for molecular sensing.

In this paper we report on a very sensitive biosensor based on gold asymmetric nanoantennas that are capable of enhancing the molecular resonances of C-H bonds. The nanoantennas are arranged as arrays of asymmetric-split H-shape (ASH) structures, tuned to produce plasmonic resonances with reflectance double peaks within the mid-infrared vibrational resonances of C-H bonds for the assay of deposited films of the molecule 17ß-estradiol (E2), used as an analyte. Measurements and numerical simulations of the reflectance spectra have enabled an estimated enhancement factor on the order of 105 to be obtained for a thin film of E2 on the ASH array. A high sensitivity value of 2335 nm/RIU was achieved, together with a figure of merit of approximately 8. Our experimental results were corroborated using numerical simulations for the C-H stretch vibrational resonances from the analyte, superimposed on the plasmonic resonances of the ASH nanoantennas.

Medical applications of infrared thermography: A review.

Abnormal body temperature is a natural indicator of illness. Infrared thermography (IRT) is a fast, passive, non-contact and non-invasive alternative to conventional clinical thermometers for monitoring body temperature. Besides, IRT can also map body surface temperature remotely. Last five decades witnessed a steady increase in the utility of thermal imaging cameras to obtain correlations between the thermal physiology and skin temperature. IRT has been successfully used in diagnosis of breast cancer, diabetes neuropathy and peripheral vascular disorders. It has also been used to detect problems associated with gynecology, kidney transplantation, dermatology, heart, neonatal physiology, fever screening and brain imaging. With the advent of modern infrared cameras, data acquisition and processing techniques, it is now possible to have real time high resolution thermographic images, which is likely to surge further research in this field. The present efforts are focused on automatic analysis of temperature distribution of regions of interest and their statistical analysis for detection of abnormalities. This critical review focuses on advances in the area of medical IRT. The basics of IRT, essential theoretical background, the procedures adopted for various measurements and applications of IRT in various medical fields are discussed in this review. Besides background information is provided for beginners for better understanding of the subject.

The influence of obesity on pulmonary rehabilitation outcomes in patients with COPD.

Although obesity is increasing in prevalence, relatively little attention has been given to its impact on outcomes in patients with chronic obstructive pulmonary disease (COPD) completing pulmonary rehabilitation. We conducted a retrospective chart review of 114 patients with COPD who completed outpatient pulmonary rehabilitation at our center. Body habitus categories were determined based on body mass index (BMI). Underweight patients (BMIA 30A kg/m(2)) were compared with non-obese patients in the following areas: forced expiratory volume in 1A s (FEV(1)) percent predicted, the 6-min walk distance (6MWD), health status, the number of unsupported arm lifts per minute, and functional performance. Health status was determined using the Self-Reported Chronic Respiratory Questionnaire (CRQ-SR), which has dimensions of dyspnea, fatigue, emotion, and mastery. Functional performance was determined using the Pulmonary Functional Status Scale Daily Activities subscore. Compared with non-obese patients, obese patients had a higher FEV(1) percent-predicted (44A +/-A 15% vs 52A +/-A 16%; PA =A 0.01), yet had lower 6MWD (269A +/-A 11 vs 203A +/-A 13; PA =A 0.0002), lower functional status, and greater fatigue at initial evaluation. However, the two groups had similar walk-work, which adjusts for differences in weight. Despite the baseline differences, both groups improved similarly following pulmonary rehabilitation (change in 6MWD was 52A +/-A 7A m in the non-obese patients versus 47A +/-A 9 in the obese patients; PA =A 0.65). Our study suggests that obese COPD patients are referred to pulmonary rehabilitation at an earlier spirometric stage of their disease, but have a poorer exercise performance, a greater degree of functional impairment and greater fatigue levels. This is probably, largely because of the effect of an increased weight burden. However, obesity did not seem to adversely affect the pulmonary rehabilitation outcomes.

The trajectory of change over multiple outcome areas during comprehensive outpatient pulmonary rehabilitation.

Although pulmonary rehabilitation has proven effectiveness in multiple outcome areas, the optimum duration of this intervention is not clear. We evaluated in an observational study the trajectory of change in upper and lower extremity exercise performance, exertional dyspnea and health status over the course of 12 weeks (24 sessions) of pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease. Demonstrating a plateau in response in these areas might be of practical use for pulmonary rehabilitation programs. We measured outcomes at baseline and at four-session (two week) intervals over the course of our comprehensive outpatient pulmonary rehabilitation program. These included treadmill endurance time at approximately 85% of initial maximal workrate, the number of arm lifts per minute, dyspnea at isotime during treadmill walking and the Chronic Respiratory Disease Questionnaire (CRQ) total score. Thirteen patients with chronic obstructure pulmonary disease (COPD) (five male, eight female) were studied; their age was 66 +/- 8 years and their FEV1 was 34 +/- 11% of predicted. Improvement was noted in all four outcome areas very early in the course of pulmonary rehabilitation. Treadmill endurance time and arm lifts increased significantly over baseline by the fourth and eighth session, respectively, and both increased in a near-linear fashion throughout pulmonary rehabilitation. Exertional dyspnea and CRQ also improved very early, with each showing a significant change from baseline by the fourth session. Their improvement, however, appeared to plateau relatively early during the course of pulmonary rehabilitation. Although the numbers studied are small and the applicability of these results to other programs is undetermined, this study does suggest that 20 or more sessions are needed for optimal acute changes in exercise performance, but improvement in dyspnea and quality of life may occur earlier.

Structural requirements for glycosaminoglycan recognition by the Lyme disease spirochete, Borrelia burgdorferi.

Borrelia burgdorferi, the Lyme disease agent, binds glycosaminoglycans (GAGs) such as heparin, heparan sulfate, and dermatan sulfate. Heparin or heparan sulfate fractions separated by size or charge were tested for their ability to inhibit attachment of B. burgdorferi to Vero cells. GAG chains of increasing length and/or charge showed increasing inhibitory potency, and detectable heparin inhibition of bacterial binding required a minimum of 16 residues. The ability of a given heparin fraction to inhibit binding to Vero cells was strongly predictive of its ability to inhibit hemagglutination, suggesting that hemagglutination reflects the capacity of B. burgdorferi to bind to GAGs.

Depolymerization of heparin by complexed ferrous ions.

Treatment of porcine heparin with the ferrous-EDTA complex and ascorbic acid for 24 h at 37 degrees C results in the degradation of most of the glycosaminoglycan to smaller fragments. About 65% of the products comprise oligosaccharides composed of less than 30 sugar units. The extent of depolymerization is decreased significantly if ascorbate or EDTA is not included in the reaction mixture. Gel filtration of the reaction products yielded fractions with narrow chain length ranges. The sulfate content of the fractions and their electrophoretic mobilities on cellulose acetate indicate that the components have equivalent charge densities. Depolymerization products with 20 or more sugar units retain significant anticoagulant potencies as measured by their effect in accelerating the neutralization of factor Xa by antithrombin.

Effect of inhaled triamcinolone on bronchial hyperreactivity and airways obstruction in asthma.

We measured changes in methacholine bronchial hyperreactivity and airways obstruction in 37 asthmatics treated with inhaled triamcinolone for 6 weeks. All received regular bronchodilator therapy but not steroids or cromolyn. Initial studies included spirometry and the provocative concentration of methacholine required to decrease the FEV1 by 20% (PC20). Patients were randomized into two groups: those given inhaled triamcinolone, 200 micrograms four times daily (T) by metered dose inhaler, and those given a placebo inhaler (P). Daily AM and PM peak flow measurements were recorded, while PC20 and pulmonary function tests were obtained at 3 and 6 weeks. Change in canister weight was used to determine treatment compliance. The PC20 of T increased from a baseline 1.00 mg/mL to 2.90 mg/mL at 6 weeks, whereas in P it decreased from 1.15 mg/mL to 1.05 mg/mL. Percent change in PC20 (delta PC20) for each patient was defined as: [(PC20(week 6)--PC20(baseline]/PC20 (baseline)] X 100. At 6 weeks, this was 290% in T versus 65% in P (P less than .05). Likewise, at 6 weeks T was significantly greater than P with respect to: delta FEV1 (4.1% versus -3.8%, P less than .05) and delta FEF25-75% (20.3% versus -5.6%, P less than .01). Patients were further separated into higher and lower complier subgroups. In T, higher compliers showed more improvement at 6 weeks than lower compliers in: delta PC20 (533.3 versus 67.8%, P less than .05), delta FEV1 (8.7 versus -1.7%, P less than .01), and delta FEF25-75% (31.9 versus 1.1%, P less than .01). These data suggest that triamcinolone improves bronchial hyperreactivity as well as airways obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril-induced hypersensitivity lung disease. An immune-complex-mediated phenomenon.

Captopril has not yet been included in the list of drugs causing hypersensitivity lung disease. We report a patient with hypertension, congestive heart failure, and chronic renal failure who, when rechallenged with captopril, developed upper lung field infiltrates associated with productive cough and striking peripheral eosinophilia. Gallium scan, transbronchial biopsy histologic findings, and direct immunofluorescent study were consistent with an immune-complex-mediated hypersensitivity reaction. There was no other etiology discovered for the patient's eosinophilia, nor was there evidence for an infectious etiology to explain his presentation.

Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD.

A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.

Preparation and characterization of NH2-terminal fibrinogen B beta fragments from N-DSK of human fibrinogen.

In order to investigate the early release of NH2-terminal plasmic fragments from the B beta chain of fibrinogen, substantial quantities of B beta 1-42 and B beta 1-21 are required as immunogens, as radioimmunoassay standards and for infusion into human volunteers to determine the half-lives of these peptides. Towards this end methods that employ selective proteolytic cleavage of these fragments from fibrinogen have been developed. Both the N-DSK fragment, produced by CNBr cleavage of fibrinogen, and B beta 1-118 were employed as substrates for plasmin with the finding of higher yields from N-DSK. B beta 1-42 and B beta 1-21 were purified by gel filtration and ion-exchange chromatography on SP-Sephadex using volatile buffers. When the purified preparation of B beta 1-42 was chromatographed on reverse-phase high performance liquid chromatography, two peaks of identical amino acid composition were separated, presumably due either to pyroglutamate or to amide differences.

Applications of high-performance liquid chromatography to the characterization of the interactions of heparin with antithrombin III and thrombin.

A rapid method for differentiating active heparin from inactive components by high-performance liquid chromatography is described. Additionally, the procedure allows for the distinction of heparin fractions with different molecular weights. The methodologies were extended to investigations on the effects of heparin in the interaction between thrombin and antithrombin III. The product formed in the presence of heparin has a characteristic retention time that is ascribed to the binding of heparin to the protein-protein complex.