988 research outputs found
Solubility enhancement of poorly water soluble drugs using liposome technology
The aim of this work is to investigate the various parameters that could control the encapsulation of lipophilic drugs and investigate the influence of the physical properties of poorly water-soluble drugs on bilayer loading. Initial work investigated on the solubilisation of ibuprofen, a model insoluble drug. Drug loading was assessed using HPLC and UV spectrophotometric analysis. Preliminary studies focused on the influence of bilayer composition on drug loading to obtain an optimum cholesterol concentration. This was followed up by studies investigating the effect of longer alkyl chain lipids, unsaturated alkyl chain lipids and charged lipids. The studies also focused on the effects of pH of the hydration medium and addition of the single chain surfactant a-tocopherol. The work was followed up by investigation of a range of insoluble drugs including flurbiprofen, indomethacin, sulindac, mefenamic acid, lignocaine and progesterone to investigate the influence of drugs properties and functional group on liposomal loading. The results show that no defined trend could be obtained linking the drug loading to the different drug properties including molecular weight, log P and other drug specific characteristics. However, the presence of the oppositely charged lipids improved the encapsulation of all the drugs investigated with a similar effect obtained with the substitution of the longer chain lipids. The addition of the single chain surfactant a-tocopherol resulted in enhancement of drug loading and possibly is governed by the log P of the drug candidate. Environmental scanning-electron microscopy (ESEM) was used to dynamically follow the changes in liposome morphology in real time during dehydration thereby providing a alternative assay of liposome formulation and stability. The ESEM analysis clearly demonstrated ibuprofen incorporation enhanced the stability of PC:Chol liposomes
Formulation, characterization and optimization of nebivolol-loaded sustained release lipospheres
Purpose: To formulate, characterize and optimize nebivolol-loaded sustained release lipospheres (LPs) using beeswax (BW) as the drug carrier.Methods: Nebivolol-loaded LPs were formulated using solvent evaporation technique (SET) and characterized. The impact of independent variables on responses such as percentage yield (PY), entrapment efficiency (EE) and drug release after 12 h (DR12) was assessed using central composite design (CCD). Numerical and graphical optimization techniques were also used to evaluate outcomes of the measured responses.Results: Twenty micron-sized (20 - 100 μm), smooth spherical LPs with good rheological properties were produced. The yield ranged from 33 (F10) to 81 % (F6), while EE ranged from 32 (F4 and F9) to 69 % (F6). The results of rheological evaluation revealed angle of repose > 24 o, Hausner’s ratio > 1.5, and Carr’s index ranging from 13 to 19 %. Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and x-ray diffraction (XRD) revealed nebivolol and BW compatibility, and the absence of possible interactions between formulation components. Duration of nebivolol release was strongly associated with BW concentration and formulation F15 showed minimum drug release (46%). Drug release was significantly higher in formulations with similar BW concentrations and low Tween-20 (T-20) concentrations (F1 and F11) than in formulations with high T-20 concentrations (F2, p < 0.05). The zeta potential of deflocculated LPs ranged from +15 to +35 mV. Nebivolol release (46 - 85 %) at pH 6.8 was significantly affected by BW concentration and it followed zero order model.Conclusion: The results obtained in this study have shown that BW is a suitable material for producing an effective sustained release formulation. The mechanism of drug release in nebivolol- loaded LPs is diffusion accompanied by erosion.Keywords: Lipospheres, Nebivolol, Beeswax, Formulation, Central composite desig
Cr-resistant rhizo- and endophytic bacteria associated with Prosopis juliflora and their potential as phytoremediation enhancing agents in metal-degraded soils
Prosopis juliflora is characterized by distinct and profuse growth even in nutritionally poor soil and environmentally stressed conditions and is believed to harbor some novel heavy metal-resistant bacteria in the rhizosphere and endosphere. This study was performed to isolate and characterize Cr-resistant bacteria from the rhizosphere and endosphere of P. juliflora growing on the tannery effluent contaminated soil. A total of 5 and 21 bacterial strains were isolated from the rhizosphere and endosphere, respectively, could tolerate Cr up to 3000 mg l-1. These isolates also exhibited tolerance to other toxic heavy metals such as, Cd, Cu, Pb and Zn, and high concentration (174 g l-1) of NaCl. Moreover, most of the isolated bacterial strains showed one or more plant growth-promoting activities. The phylogenetic analysis of the 16S rRNA gene indicated a higher and wider range of population of Cr-resistant bacteria in the endosphere than rhizosphere and the predominant species included Bacillus, Staphylococcus and Aerococcus. As far as we know, this is the first report detecting rhizo- and endophytic bacterial population associated with P. juliflora growing on the tannery effluent contaminated soil. The inoculation of three isolates to ryegrass (Lolium multiflorum L.) improved plant growth and heavy metal removal from the tannery effluent contaminated soil suggesting that these bacteria could enhance the establishment of the plant in contaminated soil and also improve the efficiency of phytoremediation of heavy metal-degraded soils
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A Framework for Dynamic Selection of Backoff Stages during Initial Ranging Process in Wireless Networks
yesThe only available solution in the IEEE 802.22 standard for avoiding collision amongst various contending customer premises equipment (CPEs) attempting to associate with a base station (BS) is binary exponential random backoff process in which the contending CPEs retransmit their association requests. The number of attempts the CPEs send their requests to the BS are fixed in an IEEE 802.22 network. This paper presents a mathematical framework that helps the BS in determining at which attempt the majority of the CPEs become part of the wireless regional area network from a particular number of contending CPEs. Based on a particular attempt, the ranging request collision probability for any number of contending CPEs with respect to contention window size is approximated. The numerical results validate the effectiveness of the approximation. Moreover, the average ranging success delay experienced by the majority of the CPEs is also determined.The full text will be available at the end of the publisher's embargo: 7th Aug 201
alpha-alpha Scattering in Halo Effective Field Theory
We study the two-alpha-particle (alpha-alpha) system in an Effective Field
Theory (EFT) for halo-like systems. We propose a power counting that
incorporates the subtle interplay of strong and electromagnetic forces leading
to a narrow resonance at an energy of about 0.1 MeV. We investigate the EFT
expansion in detail, and compare its results with existing low-energy
alpha-alpha phase shifts and previously determined effective-range parameters.
Good description of the data is obtained with a surprising amount of
fine-tuning. This scenario can be viewed as an expansion around the limit
where, when electromagnetic interactions are turned off, the Be-8 ground state
is at threshold and exhibits conformal invariance. We also discuss possible
extensions to systems with more than two alpha particles.Comment: 19 pages, 2 figures, published versio
The South Asian genome
Genetics of disease
Microarrays
Variant genotypes
Population genetics
Sequence alignment
AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)
The {\eta}'-carbon potential at low meson momenta
The production of mesons in coincidence with forward-going
protons has been studied in photon-induced reactions on C and on a
liquid hydrogen (LH) target for incoming photon energies of 1.3-2.6 GeV at
the electron accelerator ELSA. The mesons have been identified
via the decay
registered with the CBELSA/TAPS detector system. Coincident protons have been
identified in the MiniTAPS BaF array at polar angles of . Under these kinematic constraints the
mesons are produced with relatively low kinetic energy (
150 MeV) since the coincident protons take over most of the momentum of the
incident-photon beam. For the C-target this allows the determination of the
real part of the -carbon potential at low meson momenta by
comparing with collision model calculations of the kinetic energy
distribution and excitation function. Fitting the latter data for
mesons going backwards in the center-of-mass system yields a potential depth of
V = (44 16(stat)15(syst)) MeV, consistent with earlier
determinations of the potential depth in inclusive measurements for average
momenta of 1.1 GeV/. Within the experimental
uncertainties, there is no indication of a momentum dependence of the
-carbon potential. The LH data, taken as a reference to check
the data analysis and the model calculations, provide differential and integral
cross sections in good agreement with previous results for
photoproduction off the free proton.Comment: 9 pages, 13 figures. arXiv admin note: text overlap with
arXiv:1608.0607
Agents increasing cyclic GMP amplify 5-HT4-elicited positive inotropic response in failing rat cardiac ventricle
Activation of 5-HT4 receptors in failing ventricles elicits a cAMP-dependent positive inotropic response which is mainly limited by the cGMP-inhibitable phosphodiesterase (PDE) 3. However, PDE4 plays an additional role which is demasked by PDE3 inhibition. The objective of this study was to evaluate the effect of cGMP generated by particulate and soluble guanylyl cyclase (GC) on the 5-HT4-mediated inotropic response. Extensive myocardial infarctions were induced by coronary artery ligation in Wistar rats, exhibiting heart failure 6 weeks after surgery. Contractility was measured in left ventricular preparations. Cyclic GMP was measured by EIA. In ventricular preparations, ANP or BNP displayed no impact on 5-HT4-mediated inotropic response. However, CNP increased the 5-HT4-mediated inotropic response as well as the β1-adrenoceptor (β1-AR)-mediated response to a similar extent as PDE3 inhibition by cilostamide. Pretreatment with cilostamide eliminated the effect of CNP. Inhibition of nitric oxide (NO) synthase and soluble GC by l-NAME and ODQ, respectively, attenuated the 5-HT4-mediated inotropic response, whereas the NO donor Sin-1 increased this response. The effects were absent during PDE3 inhibition, suggesting cGMP-dependent inhibition of PDE3. However, in contrast to the effects on the 5-HT4 response, Sin-1 inhibited whereas l-NAME and ODQ enhanced the β1-AR-mediated inotropic response. cGMP generated both by particulate (NPR-B) and soluble GC increases the 5-HT4-mediated inotropic response in failing hearts, probably through inhibition of PDE3. β1-AR and 5-HT4 receptor signalling are subject to opposite regulatory control by cGMP generated by soluble GC in failing hearts. Thus, cGMP from different sources is functionally compartmented, giving differential regulation of different Gs-coupled receptors
Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.
OBJECTIVE
To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach.
MATERIALS AND METHODS
In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6-12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease.
RESULTS
267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019).
CONCLUSION
Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours
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