Peppering versus Single Injection Technique in Tennis Elbow - A Prospective Comparative Study.

Introduction: Lateral epicondylitis is a common condition causing severe incapacitating pain. Several methods of treatment have been approached for its management. In our study we aim to compare the results of injecting steroid and lignocaine mixture via single injection and peppered injection technique and analyse the outcome in each category. Materials and methods: A prospective randomised study comprising of 25 patients in each group (single vs peppered group) were included in the study after satisfying inclusion and exclusion criteria. Outcome of the treatment was measured in the form of Patient Related Tennis Elbow Evaluation (PRTEE) Questionnaire, Visual analogue score (VAS) and tenderness grading at two weeks, six weeks and six months after injection. Results: Results of our study showed that the mean PRTEE score was 22.36, 18.40 and 14.16 at 2 weeks, 6 weeks and 6 months following peppered injection as compared to 28.96, 21.84 and 25.32 in the single injection group (p value <0.05). VAS score at 2 weeks, 6 weeks and 6 months after the peppered injection was found to be 2.72, 1.72 and 1.36 and in the single injection group was 2.96, 1.92 and 2.72 at 2weeks, 6 weeks and 6 months, respectively (p value <0.05). On comparison of the 2 groups, there was a significant reduction of VAS scores at 6 months post-injection (p value <0.05) and PRTEE score at 6 weeks, 6 months in peppered injection group. Conclusion: The effects of peppered injection technique is seen to be advantageous over the single injection technique in the management of chronic lateral epicondylitis.

Approaches to maintenance dosing during oral immunotherapy.

Long term daily dosing for patients and families may be challenging due to food aversions, dosing protocols, and age of the patient. The few long term studies suggest that low quantity daily dosing is associated with passing higher dose challenges over the long term, whereas high dose maintenance may protect for longer avoidance intervals. We review the data for peanut and suggest several strategies for your patients.

Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1ß mediated articular cartilage matrix destruction.

OBJECTIVE: Cartilage health is maintained in response to a range of mechanical stimuli including compressive, shear and tensile strains and associated alterations in osmolality. The osmotic-sensitive ion channel Transient Receptor Potential Vanilloid 4 (TRPV4) is required for mechanotransduction. Mechanical stimuli inhibit interleukin-1ß (IL-1ß) mediated inflammatory signalling, however the mechanism is unclear. This study aims to clarify the role of TRPV4 in this response. DESIGN: TRPV4 activity was modulated glycogen synthase kinase (GSK205 antagonist or GSK1016790 A (GSK101) agonist) in articular chondrocytes and cartilage explants in the presence or absence of IL-1ß, mechanical (10% cyclic tensile strain (CTS), 0.33 Hz, 24hrs) or osmotic loading (200mOsm, 24hrs). Nitric oxide (NO), prostaglandin E2 (PGE2) and sulphated glycosaminoglycan (sGAG) release and cartilage biomechanics were analysed. Alterations in post-translational tubulin modifications and primary cilia length regulation were examined. RESULTS: In isolated chondrocytes, mechanical loading inhibited IL-1ß mediated NO and PGE2 release. This response was inhibited by GSK205. Similarly, osmotic loading was anti-inflammatory in cells and explants, this response was abrogated by TRPV4 inhibition. In explants, GSK101 inhibited IL-1ß mediated NO release and prevented cartilage degradation and loss of mechanical properties. Upon activation, TRPV4 cilia localisation was increased resulting in histone deacetylase 6 (HDAC6)-dependent modulation of soluble tubulin and altered cilia length regulation. CONCLUSION: Mechanical, osmotic or pharmaceutical activation of TRPV4 regulates HDAC6-dependent modulation of ciliary tubulin and is anti-inflammatory. This study reveals for the first time, the potential of TRPV4 manipulation as a novel therapeutic mechanism to supress pro-inflammatory signalling and cartilage degradation.

Comprehensive study of interaction between biocompatible PEG-InP/ZnS QDs and bovine serum albumin.

Polyethylene glycol (PEG) surface modified biocompatible InP/ZnS quantum dots (QDs) act as a potential alternative for conventional carcinogenic cadmium-based quantum dots for in vivo and in vitro studies. Comprehensively, we studied the interaction between a model protein bovine serum albumin (BSA) and PEGylated toxic free InP/ZnS QDs using various spectroscopic tools such as absorption, fluorescence quenching, time resolved and synchronous fluorescence spectroscopic measurements. These studies principally show that tryptophan (Trp) residues of BSA have preferable binding affinity towards PEG-InP/ZnS QDs surface and a blue shift in Trp fluorescence emission is a signature of conformational changes in its hydrophobic microenvironment. Photoluminescence (PL) intensity of Trp is quenched by ground state complex formation (static quenching) at room temperature. However, InP/ZnS@BSA conjugates become unstable with increasing temperature and PL intensity of Trp is quenched via dynamic quenching by PEG-InP/ZnS QDs. Experimentally determined thermodynamic parameters for these conjugates have shown spontaneity, entropy driven and exothermic nature of bio-conjugation. The calculated binding affinity (n ≅ 1, Hill coefficient) suggest that the affinity of InP/ZnS QDs for a BSA protein is not dependent on whether or not other BSA proteins are already bound to the QD surface. Energy transfer efficiency (E), Trp residue to InP/ZnS QDs distances and energy transfer rate (kT ) were all obtained from FÖrster resonance energy.

Interaction and energy transfer studies between bovine serum albumin and CdTe quantum dots conjugates: CdTe QDs as energy acceptor probes.

In this paper, a systematic investigation of the interaction of bovine serum albumin (BSA) with water-soluble CdTe quantum dots (QDs) of two different sizes capped with carboxylic thiols is presented based on steady-state and time-resolved fluorescence measurements. Efficient Förster resonance energy transfer (FRET) was observed to occur from BSA donor to CdTe acceptor as noted from reduction in the fluorescence of BSA and enhanced fluorescence from CdTe QDs. FRET parameters such as Förster distance, spectral overlap integral, FRET rate constant and efficiency were determined. The quenching of BSA fluorescence in aqueous solution observed in the presence of CdTe QDs infers that fluorescence resonance energy transfer is primarily responsible for the quenching phenomenon. Bimolecular quenching constant (kq ) determined at different temperatures and the time-resolved fluorescence data provide additional evidence for this. The binding stoichiometry and various thermodynamic parameters are evaluated by using the van 't Hoff equation. The analysis of the results suggests that the interaction between BSA and CdTe QDs is entropy driven and hydrophobic forces play a key role in the interaction. Binding of QDs significantly shortened the fluorescence lifetime of BSA which is one of the hallmarks of FRET. The effect of size of the QDs on the FRET parameters are discussed in the light of FRET parameters obtained.

Effect of quencher and temperature on fluorescence intensity of laser dyes: DETC and C504T.

Fluorescence quenching of 7- Diethylamino-3-thenoylcoumarin (DETC) and 2,3,6,7-tetrahydro-1,1,7,7-tetramethyl11-oxo-1H,5H,11H- [1]benzopyrano[6,7,8-ij]quinolizine-10-carboxylic acid, ethyl ester (C504T) by aniline(AN), dimethylaniline (DMA) and diethylaniline (DEA) was investigated in toluene by steady state and transient methods. The quenching parameters like frequency of encounter (kd), probability of quenching per encounter (p), quenching rate parameters (kq) and activation energy of quenching (Ea) were determined experimentally. The kq values determined by steady state and time-resolved methods for the both dyes were found to be same, indicating the dynamic nature of interaction. Magnitudes of p and Ea suggested that the quenching reaction is predominantly controlled by material diffusion. The quenching mechanism is rationalized in terms of electron transfer (ET) from donors (aromatic amines) to the acceptors (coumarin derivatives) confirmed by correlating kq with free energy changes (ΔG°). Further, an effect of temperature on fluorescence intensity was carried out in toluene and methanol solvents. Fluorescence intensity of both the dyes decreases with increase in temperature. Temperature quenching in case of C504T is due to intersystem crossing S1→T2, whereas for DETC, quenching is due to intersystem crossing S1→T2 and ICT→TICT transition.

Spectroscopic investigation of water-soluble alloyed QDs with bovine serum albumin.

We present here a systematic investigation on the interaction between a water-soluble alloyed semiconductor quantum dot and bovine serum albumin using various spectroscopic techniques i.e. fluorescence quenching, resonance light scattering and synchronous fluorescence spectroscopy. The analysis of fluorescence spectrum and fluorescence intensity indicates that the intrinsic fluorescence of bovine serum albumin (BSA) gets quenched by both static and dynamic quenching mechanism. The Stern-Volmer quenching constants, energy transfer efficiency parameters, binding parameters and corresponding thermodynamic parameters (ΔH0 , ΔS0 and ΔG0 ) have been evaluated by using van 't Hoff equation at different temperatures. A positive entropy change with a positive enthalpy change was observed suggesting that the binding process was an entropy-driven, endothermic process associated with the hydrophobic effect. The intermolecular distance (r) between donor (BSA) and acceptor (CdSeS/ZnS quantum dots) was estimated according to Förster's theory of non-radiative energy transfer. The synchronous fluorescence spectra revealed a blue shift in the emission maxima of tryptophan which is indicative of increasing hydrophobicity. Negative ΔG0 values implied that the binding process was spontaneous. It was found that hydrophobic forces played a role in the quenching process. Copyright © 2016 John Wiley & Sons, Ltd.

Spectroscopic investigation of alloyed quantum dot-based FRET to cresyl violet dye.

Quantum dots (QDs), bright luminescent semiconductor nanoparticles, have found numerous applications ranging from optoelectronics to bioimaging. Here, we present a systematic investigation of fluorescence resonance energy transfer (FRET) from hydrophilic ternary alloyed quantum dots (CdSeS/ZnS) to cresyl violet dye with a view to explore the effect of composition of QD donors on FRET efficiency. Fluorescence emission of QD is controlled by varying the composition of QD without altering the particle size. The results show that quantum yield of the QDs increases with increase in the emission wavelength. The FRET parameters such as spectral overlap J(λ), Förster distance R0, intermolecular distance (r), rate of energy transfer k(T)(r), and transfer efficiency (E) are determined by employing both steady-state and time-resolved fluorescence spectroscopy. Additionally, dynamic quenching is noticed to occur in the present FRET system. Stern-Volmer (K(D)) and bimolecular quenching constants (k(q)) are determined from the Stern-Volmer plot. It is observed that the transfer efficiency follows a linear dependence on the spectral overlap and the quantum yield of the donor as predicted by the Förster theory upon changing the composition of the QD.

Estimation of ground and excited state dipole moment of laser dyes C504T and C521T using solvatochromic shifts of absorption and fluorescence spectra.

The absorption and fluorescence spectra of laser dyes: coumarin 504T (C504T) and coumarin 521T (C521T) have been recorded at room temperature in a series of non-polar and polar solvents. The spectra of these dyes showed bathochromic shift with increasing in solvent polarity indicating the involvement of π→π⁎ transition. Kamlet-Taft and Catalan solvent parameters were used to analyze the effect of solvents on C504T and C521T molecules. The study reveals that both general solute-solvent interactions and specific interactions are operative in these two systems. The ground state dipole moment was estimated using Guggenheim's method and also by quantum mechanical calculations. The solvatochromic data were used to determine the excited state dipole moment (µ(e)). It is observed that dipole moment value of excited state (µ(e)) is higher than that of the ground state in both the laser dyes indicating that these dyes are more polar in nature in the excited state than in the ground state.

Design, Synthesis and Optoelectronic Properties of Unsymmetrical Oxadiazole Based Indene Substituted Derivatives as Deep Blue Fluoroscent Materials.

A series of novel unsymmetrically substituted indene-oxadiazole derivatives (3a-f) have been designed and synthesized by employing palladium catalysed Suzuki cross coupling reaction in high yields. The structural integrity of all the novel compounds was established by (1)H, (13)C NMR and LC/MS analysis. These compounds are amorphous in nature and are remarkably stable to long term storage under ambient conditions. The optoelectronic properties have been studied in detail using UV-Vis absorption and Fluorescence spectroscopy. All compounds emit intense blue to green-blue fluoroscence with high quantum yields. Time resolved measurments have shown life times in the range of 1.28 to 4.51 ns. The density functional theory (DFT) calculations were carried out for all the molecules to understand their structure-property relationships. Effect of concentration studies has been carried out in different concentrations for both absorption and emission properties and from this we have identified the optimized fluoroscence concentrations for all these compounds. The indene substituted anthracene-oxadiazole derivative (3f) showed significant red shift (λmax (emi) = 490 nm) and emits intense green-blue fluoroscence with largest stokes shift of 145 nm. This compound also exhibited highest fluoroscence life time (τ) of 4.51 ns, which is very close to the standard dye coumarin-540A (4.63 ns) and better than fluorescein-548 (4.10 ns). The results demonstrated that the novel unsymmetrical indene-substituted oxadiazole derivatives could play important role in organic optoelectronic applications, such as organic light-emitting diodes (OLEDs) or as models for investigating the fluorescent structure-property relationship of the indene-functionalized oxadiazole derivatives.

Solvents effect on the absorption and fluorescence spectra of 7-diethylamino-3-thenoylcoumarin: evaluation and correlation between solvatochromism and solvent polarity parameters.

Effect of solvents of varying polarities on absorption and fluorescence spectra and dipole moment of laser dye: 7-diethylamino-3-thenoylcoumarin (DETC) has been investigated. A small band shift is obtained in the absorption spectra compared to emission spectra. The spectral shifts were correlated with Catalan's parameters using linear solvation energy relationship. It reveals that non-specific interaction measured by solvent polarity has more influence on absorption and solvent dipolarity contribution is significant in case of fluorescence. A bathochromic shift observed in absorption and emission spectra with increasing solvent polarity, which implied that the transition involved is π→π(∗). The solvatochromic correlations were used to estimate the excited state dipole moment using experimentally determined ground state dipole moment. The observed single-state excited state dipole moment is found to be greater than the ground state.

Beneficial effects of nebivolol in comparison with atenolol on safety and tolerability in essential hypertension.

INTRODUCTION: Hypertension, "The silent killer" is a multifactorial disorder which is asymptomatic and if left untreated leads to lethal complications. Nebivolol is a third generation beta blocker with additional vasodilating property due to nitric oxide release. AIM: The current study aims to assess efficacy and safety of Nebivolol and compare with Atenolol. METHODS: This was prospective, double blind, comparative controlled clinical study. Total 90 patients were enrolled into study as per selection criteria. Patients were randomized to receive Atenolol and Nebivolol with 45 patients in each group for 12 weeks. RESULTS AND CONCLUSION: The mean reduction diastolic blood pressure in Nebivolol and Atenolol group was 10.77±2.60 and 10.05±2.83 respectively. The number of patients with adverse effect events was higher in the Atenolol than in the Nebivolol group (36.84% of Atenolol Vs 12.82% of Nebivolol). Thus it can be concluded that, for the same antihypertensive effect, Nebivolol was better tolerated than Atenolol.

Determination of ground and excited state dipole moments of dipolar laser dyes by solvatochromic shift method.

The absorption and fluorescence spectra of three medium sized dipolar laser dyes: coumarin 478 (C478), coumarin 519 (C519) and coumarin 523 (C523) have been recorded and studied comprehensively in various solvents at room temperature. The absorption and fluorescence spectra of C478, C519 and C523 show a bathochromic and hypsochromic shifts with increasing solvent polarity indicate that the transitions involved are π→π(∗) and n→π(∗). Onsager radii determined from ab initio calculations were used in the determination of dipole moments. The ground and excited state dipole moments were evaluated by using solvatochromic correlations. It is observed that the dipole moment values of excited states (µe) are higher than corresponding ground state values (µg) for the solvents studied. The ground and excited state dipole moments of these probes computed from ab initio calculations and those determined experimentally are compared and the results are discussed.

Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment.

This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Young's modulus of ∼5 kPa. This is notably greater than that reported for isolated chondrocytes in suspension. The increase in cell modulus occurs over a 24-h period and is associated with an increase in the organization of the cortical actin cytoskeleton, which is known to regulate cell mechanics. However, there was a reduction in chromatin condensation, suggesting that changes in the nucleus mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed that cells in the stiffer gels rapidly develop a higher Young's modulus of ∼20 kPa, sixfold greater than that observed in the softer gels. This was associated with higher levels of actin organization and chromatin condensation, but only after 24 h in culture. Further studies revealed that cells in stiffer gels synthesize less extracellular matrix over a 28-day culture period. Hence, this study demonstrates that the properties of the three-dimensional microenvironment regulate the mechanical, structural, and metabolic properties of living cells.

Sclerotium rolfsii lectin inhibits proliferation and induces apoptosis in human ovarian cancer cell line PA-1.

OBJECTIVES: Sclerotium rolfsii lectin (SRL), isolated from soil born phytopathogenic fungus Sclerotium rolfsii, exhibits exquisite binding specificity to the oncofoetal Thomsen-Friedenreich (Galß1,3GalNAcα-O-Ser/Thr, T or TF) antigen and associated glycans. In the present study, we report anti-proliferative activity of SRL and investigate underlying mechanisms of SRL-induced apoptosis, in the human ovarian cancer cell line PA-1. MATERIALS AND METHODS: SRL-induced anti-proliferative effects were determined using MTT assay and induction of apoptosis was determined by flow cytometry, confocal microscopy and western blot analysis. RESULTS: SRL inhibited population growth of PA-1 cells in a dose- and time-dependent manner with maximum inhibition (71.3 ± 1.9%) occurring at concentration of 50 µg/ml after 72 h incubation. Observed effects of SRL could be blocked by competing glycoproteins, asialomucin, mucin and fetuin. Treatment with SRL resulted in increase in hypodiploid cell population as determine by cell cycle analysis. Increase in numbers of annexin V-PI positive cells, and cleavage of PARP confirmed apoptosis-inducing activity of SRL. Involvement of caspases in SRL-mediated apoptosis was determined by cleavage of caspases-3, -8 and -9 in a time-dependent manner, thereby suggesting possible involvement of both intrinsic and extrinsic caspase-dependent pathways. CONCLUSION: The present study demonstrates anti-proliferative and apoptosis-inducing activity of SRL that can be exploited for potential application in ovarian cancer research.

Gonadotropin levels in hypothyroid women of reproductive age group.

OBJECTIVE: To study serum gonadotropin (FSH, LH) levels in cases of subclinical and overt hypothyroid women in reproductive age group. MATERIAL AND METHOD: Female patients of reproductive age group attending thyroid clinic of Acharya Vinoba Bhave Hospital were included in the study. Detail menstrual history was taken, and serum FSH and LH levels were estimated by radio immuno assay method. RESULT: Eighty patients were included in the study, out of whom 46 (57.5%) had subclinical hypothyroidism and 34 (42.5%) had overt hypothyroidism. In subclinical hypothyroidism group the menstrual dysfunction which dominated in our study was oligomenorrhea (28.2%) followed by menorrhagia (17.39%). 39.13% had normal menstruation. In overt hypothyroidism group again it was oligomenorrhoea (23.5%) which was the principal menstrual abnormality followed by menorrhagia (17.64%). The percentage of females with normal menstruation was 47.05%. The levels of serum FSH and LH were significantly low in cases of both subclinical and overt hypothyroid women. They were significantly low when done between day 2 and 5 of the cycle. CONCLUSION: Hypothyroidism decreases levels of serum FSH and serum LH. Subclinical hypothyroidism is one of the major etiological factors of infertility. Autoantibodies against thyroid should be searched for in cases of female patients with infertility.

Restructuring with the middle-management advantage.

The strategic roles enabling conditions and intermediate outcomes of middle managers during a period of organizational restructuring were examined, with focus on developing an understanding of how senior management can best enable middle managers to achieve radical change. The case method was used, and data were collected from interviews with both middle and senior managers. Results revealed considerable differences between executives and middle managers with regard to middle management's strategic roles, enabling conditions and outcomes. Findings suggest that the 2 groups have different perceptions on how best to support middle management in strategic roles, especially during a crisis. Senior managers felt that middle managers required much explanation and guidance concerning the restructuring effort, viewing middle managers as primarily implementers. Middle managers viewed themselves in a more active role as providers of information necessary in guiding the restructuring decisions. In the area of intermediate outcomes, senior managers emphasized gaining consensus from middle managers to support implementation, but middle managers valued the outcome of securing agency over their own work to act in the best interests of the organization. Thus, middle managers can add value during a time of restructuring by matching strategic roles, enabling conditions and intermediate outcomes with the requirements of the strategic change.

Glatiramer acetate: successful desensitization for treatment of multiple sclerosis.

BACKGROUND: Glatiramer acetate is an immunomodulatory drug that is widely prescribed for the treatment of multiple sclerosis. It is frequently associated with local injection site reactions and generalized urticaria. It is also associated with immediate postinjection systemic reactions in approximately 10% of patients. To our knowledge, no desensitization protocols for glatiramer acetate have been published to date. OBJECTIVES: To evaluate the safety and efficacy of glatiramer acetate desensitization in a series of patients with multiple sclerosis. METHODS: Six patients with multiple sclerosis and glatiramer acetate-associated local or systemic reactions underwent a 4-hour outpatient desensitization procedure at Cleveland Clinic between 2003 and 2008. Beginning with 20 ng, we administered subcutaneous glatiramer acetate suspension in increasing dosages every 15 minutes. Patient outcomes were monitored by return clinic visit and telephone follow-up. RESULTS: No episodes of anaphylaxis or serious adverse reactions occurred during or immediately after desensitization. One patient suspended therapy after 14 months due to persistent local injection site reactions. All other patients successfully continued glatiramer acetate therapy. CONCLUSION: Glatiramer acetate offers significant benefit to patients with multiple sclerosis. Our experience suggests that patients who suspend its use owing to local or systemic reactions can be successfully and safely desensitized and can resume medication use. To our knowledge, this is the first report of successful desensitization to glatiramer acetate in patients with multiple sclerosis.

Rotational diffusion of coumarins in aqueous DMSO.

The rotational dynamics of four structurally similar polar molecules viz., coumarin 440, coumarin 450, coumarin 466 and coumarin 151 has been studied in binary mixtures comprising of dimethyl sulphoxide and water at room temperature using the steady state fluorescence depolarization method and time correlated single photon counting technique. The binary mixtures are characterized by the fact that at a particular composition the viscosity (eta) of the solution reaches a maximum value that is higher than the viscosities of either of the two co-solvents. The dielectric properties of the solution change across the composition range and the qualitative features of the solvent relaxation dynamics in complex systems are known to differ from those in simple solutions. A hook type profile of rotational reorientation time (tau(r)) vs viscosity (eta) is obtained for all the solutes in dipolar aprotic mixture of dimethyl sulphoxide-water, with the rotational reorientation times being longer in organic solvent-rich zone, compared to the corresponding isoviscous point in water-rich zone due to strong hydrogen bonding. Fluorescence lifetimes as well as rotational reorientation times are sensitive to the composition of the binary solvent system under study than to the viscosity suggesting the importance of local structure. The results are discussed in the light of hydrodynamic and dielectric friction models.

Role of diagnostic hysteroscopy in abnormal uterine bleeding and its histopathologic correlation.

AIMS AND OBJECTIVES: To study the accuracy of hysteroscopy in evaluation of abnormal uterine bleeding and to correlate hysteroscopic findings with histopathologic findings. MATERIALS AND METHODS: A prospective study was carried out in the Department of Obstetrics and Gynecology at AVBRH and JNMC, Sawangi (M), Wardha, from May 2006 to September 2008. One hundred cases were selected for this study from patients of age group 18 and above, who were admitted with the history of abnormal uterine bleeding. Hysteroscopic examination was done in all patients post-menstrually, whenever possible, except in those cases where menstrual cycles were grossly irregular or patients came with continuous bleeding per vaginum. The patients then underwent dilatation and curettage and endometrium was sent for histopathologic examination. The correlation between findings on hysteroscopy and histopathologic examination was tabulated. RESULTS: FOLLOWING WERE THE FINDINGS ON HYSTEROSCOPY: proliferative 34%, secretary 16%, hyperplasia 18%, atrophic 8%, endometrial polyp 9%, submucous myoma 11%, carcinoma of endometrium 03%, misplaced Cu-T 1%. CONCLUSION: In patients with abnormal uterine bleeding, hyster-oscopy provides more accurate dia-gnosis than dilatation and curettage.