A single subcutaneous administration of a sustained-release ivermectin suspension eliminates Psoroptes cuniculi infection in a rabbit farm

Abstract

Background: Psoroptes cuniculi mites are the most common ear parasites infesting breeding female rabbits. The suffering rabbits show cutaneous signs of the infestation in the ears and are prone to secondary infections.

Objectives: This trial was conducted to eliminate P. cuniculi in farm rabbits with a sustained-release ivermectin-loaded solid dispersion suspension (IVM-SD) suspension, and studied the stability of the formulation.

Animals: There were 986 breeding female Hyplus rabbits naturally infected with P. cuniculi.

Methods: All rabbits infected with P. cuniculi were subcutaneously administered with a single dose of IVM-SD suspension at 2?mg/kg body weight. Twenty-seven rabbits with severe infections were observed daily and examined on days 0 and 14 to score the lesions and count mites in crusts.

Results: Fourteen days after the treatment no live mites were detected, demonstrating 100% therapeutic efficacy. The mean lesion scores decreased from 4.33 to 0.11 in the left ears and from 4.22 to 0.22 in the right ears. No reinfection occurred within 60?days of treatment.

Conclusions: A single subcutaneous administration of the IVM-SD suspension at 2?mg/kg was effective in eliminating P. cuniculi infection in the rabbit farm.     

Nonlinear quantum optical computing via measurement

Abstract

We show how the measurement induced model of quantum computation proposed by Raussendorf and Briegel (2001, Phys. Rev. Letts., 86, 5188) can be adapted to a nonlinear optical interaction. This optical implementation requires a Kerr nonlinearity, a single photon source, a single photon detector and fast feed forward. Although nondeterministic optical quantum information proposals such as that suggested by KLM (2001, Nature, 409, 46) do not require a Kerr nonlinearity they do require complex reconfigurable optical networks. The proposal in this paper has the benefit of a single static optical layout with fixed device parameters, where the algorithm is defined by the final measurement procedure.     

In vitro and in vivo effects of morin on the intestinal absorption and pharmacokinetics of olmesartan medoxomil solid dispersions

Abstract

Purpose: In-situ evaluation to corroborate morin effects on the intestinal absorption and pharmacokinetic behavior of freeze-dried OLM-loaded solid dispersions with Caco-2 and in-vivo studies

Methods: Intestinal transport and absorption studies were examined by Caco-2 permeability, in-situ single pass perfusion and closed-loop models along with in-vivo pharmacokinetic studies to evaluate and confirm the effect of P-gp-mediated activity of morin. We evaluated the intestinal membrane damage in the presence of morin by measuring the release of protein and lactate dehydrogenase (LDH) followed by using qualitative and quantitative morphometric analysis to describe the surface characteristics of intestinal epithelium.

Results: Morin showed the highest P_eff value 13.8?±?0.34?×?10^?6?cm/s in jejunum than ileum (p?<?.01) at 100?µM with absorption enhancement of 1.31-fold together with enhanced (p?<?.01) secretory transport of 6.27?±?0.27?×?10?^?6?cm/s in Caco-2 monolayer cells. Our findings noticed 2.37 (in-situ); 2.39 (in-vivo) and 1.43 (in-situ); 1.36 (in-vivo) fold increase in AUC_0–t with elevated C_max and shortened T_max for freeze-dried solid dispersion in the presence of morin as compared to pure OLM and freeze-dried solid dispersions without morin, respectively.

Conclusions: Our study demonstrated that increased solubilization through freeze-dried OLM-loaded solid dispersion together with efflux inhibition improved intestinal permeability to one system that might lead to novel solubilization and efflux pump inhibition as a novel alternative potential to increase oral absorption and bioavailability of OLM.     

Single Crystals Synthesis and Refinement of the Crystal Structure of the Polymerized Tetragonal Phase of C60

Abstract

The possibilities of single crystals synthesis in conditions of nonisotropic one‐axis contraction were studied. As a result of the work the single crystals of the tetragonal polymerized phase of C₆₀ without orientational domains were obtained. The crystal structure of this phase was resolved using single crystal x‐ray diffraction data. A structural model of this phase proposed early was confirmed and refined to final R = 0.075. The structure is slightly disordered. It consists of a random combination of the P 4 ₂/mmc layers (84%) and of the Immm layers (16%), along the c axis.     

Current Perspectives on the Physics of Trapped Ions

Abstract

This paper presents a survey of recent work in the field of the physics of trapped ions, as an introduction to this Journal of Modern Optics special issue. The contrasting properties of trapped ion clouds and the single trapped ion are highlighted, together with their application to frequency standards and fundamental measurements.     

Cryocornea – toward enhancing the capacity and throughput of ex vivo corneal model

Abstract

Objective: The objective of this study was to investigate the effects of the concentration of two intracellular (i.e. propylene glycol and glycerol) and four extracellular (i.e. dextran, hydroxypropyl methylcellulose, polyvinylpyrolidone, trehalose) cryoprotective agents as well as the effects of freeze-thawing procedures on the corneal cryoprotection.

Significance: The corneal cryopreservation may possibly become the long-term storage technique of choice for collection of animal corneas suitable for ex vivo drug testing.

Methods: The integrity of corneal barrier was evaluated by measurements of transepithelial electrical resistance.

Results: Under the investigated experimental conditions the best result was obtained for slow freezing (2?h at ?20?°C followed by 46?h at ?70?°C) and rapid thawing (0.25?h at 34?°C) procedure where 20% (w/V) trehalose in Krebs Ringer buffer solution was used as extracellular cryoprotective agent.

Conclusions: The selection of corneal freeze-thawing protocol as well as the optimal type and concentration of a cryoprotective agent allows the cryostorage of porcine corneal tissues with suitable TEER properties (cryocornea).     

Interferometric Measurements of Phase Singularities in the Output of a Visible Laser

Abstract

We report the use of a simple interferometric technique which allows direct identification of phase singularities in laser fields. Phase singularities are observed in families of optical patterns formed via cooperative frequency mode locking in a continuous single longitudinal mode Na₂ ring laser. The interferometric technique complements a previously reported astigmatic imaging method, and is superior in that it can be used to elucidate the structure of the higher order stationary patterns.     

Quantum shell game: Finding the hidden pea in a single attempt

Abstract

A quantum search of a database of four elements can be carried out in a single run with unit success probability. The classical analogy is to finding a pea hidden under one of four nut shells in a single attempt. We consider the algorithm in a system composed of two qubits, and show how the one and two-qubit search transforms are related to Pauli spin operators. The key search operation, the inversion about the mean, appears as a spatially rotated two-qubit phase shift, which provides some physical intuition for how it is implemented.     

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin

Abstract

Objective: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability.

Methods: In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin.

Results: As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague–Dawley rats, the optimized SNEDDS of curcumin–phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS.

Conclusion: The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.     

Microstructure and properties of AlTiNiMnBx high entropy alloys

Abstract

AlTiNiMnB _x (x=0˙1, 0˙2, 0˙4 and 0˙5) high entropy alloys are prepared by an arc furnace. The results show that the alloys have a single bcc crystal structure. Boron additions lead to distortion of the crystal lattice and alloy strengthening. The highest hardness (779 HV) is achieved with 0˙5 at.-%B.     

Prediction of area under the curve for a p-glycoprotein,a CYP3A4 and a CYP2C9 substrate using a single time point strategy: assessment using fexofenadine,itraconazole and losartan and metabolites

Abstract

Background: In the present age of polypharmacy, limited sampling strategy becomes important to verify if drug levels are within the prescribed threshold limits from efficacy and safety considerations. The need to establish reliable single time concentration dependent models to predict exposure becomes important from cost and time perspectives.

Methods: A simple unweighted linear regression model was developed to describe the relationship between C_max versus AUC for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole. The fold difference, defined as the quotient of the observed and predicted AUC values, were evaluated along with statistical comparison of the predicted versus observed values.

Results: The correlation between C_max versus AUC was well established for all the five drugs with a correlation coefficient (r) ranging from 0.9130 to 0.9997. Majority of the predicted values for all the five drugs (77%) were contained within a narrow boundary of 0.75- to 1.5-fold difference. The r values for observed versus predicted AUC were 0.9653 (n?=?145), 0.8342 (n?=?76), 0.9524 (n?=?88), 0.9339 (n?=?89) and 0.9452 (n?=?66) for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole, respectively.

Conclusions: C_max versus AUC relationships were established for all drugs and were amenable for limited sampling strategy for AUC prediction. However, fexofenadine, EXP3174 and hydroxyitraconazole may be most relevant for AUC prediction by a single time concentration as judged by the various criteria applied in this study.     

Addressing for letter‐oriented keys

Abstract

This paper presents a new algorithm for hashing. In this approach each key (x, y) is denoted as a pair of letters, and it is extracted from each letter‐oriented key in the key space according to a certain pre‐determined extraction algorithm. For the keys (x, y), our hashing function hashes as follows:

These functions allow single probe retrieval from minimally sized space of letter‐oriented keys. Various areas can be applied, such as searching reserved words in compilers and filtering frequently used words in natural language processing.     

Quasi-static fracture toughness testing of a single CT specimen at two test conditions

Abstract

It is proposed that a single CT specimen can be used for determining J ₀.₂ at two testing conditions, provided it can be ensured that the crack tip plastic zones for the two tests do not interfere. This is achieved by extending the crack at the end of the first fracture test by fatigue cycling at ambient temperature to obtain the starting crack for the second test. This method has been validated by testing thermally aged CT specimens of modified 9Cr - 1Mo steel at 653 K and 803 K. The J-Δa values obtained by a multispecimen method at a specific temperature were on a single curve irrespective of whether the data were generated from the first test or second test on that sample. Also, the J-Δa curves obtained using a single specimen normalisation method from data on first and second tests were within the expected specimen to specimen variation.     

Preparation and evaluation of HPMC-based pirfenidone solution in vivo

Abstract

Context: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability.

Objective: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops.

Materials and methods: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution.

Results: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20?min (p?<?.01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90?min after topical administration.

Conclusions: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.     

In the Chase of Mixed Halofullerenes: Remarkable Transformation of C60Cl n (n = 6, 8, 12, 14) to C60Br24

Abstract

Chlorofullerenes C₆₀Cl _n (n = 6, 8, 12, 14) were found to react with bromine yielding C₆₀Br₂₄ as a single product. No intermediates containing both bromine and chlorine atoms attached to the cage were detected in the course of transformation.     

Phase properties of coherent phase and generalized geometric states

Abstract

We examine some properties of a class of partial phase states of a single field mode. The quasiprobability distribution function and the phase properties of both the generalized geometric and even geometric states are investigated. The relation between the coherent phase states and the SU(1, 1) coherent states is sought.     

The Jaynes-Cummings Model with a q Analogue of a Coherent State

Abstract

In this paper we study the time evolution of the atomic inversion of the two-level atom which is coupled to the q analogue of a single mode of the bosonic field. The q field under consideration is supposed to be prepared initially in the q analogue of Glauber's coherent state. We find that q deformation of Heisenberg algebra may correspond to some effective nonlinear interaction of the cavity mode.     

Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate

Context: Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids.

Objectives: The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects.

Methods: Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis.

Results: SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study,?>?80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T_max?=?0.97?h, C_max?=?118.28?µg/mL of HSS; T_max?=?2.16?h, C_max?=?64.47?µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis.

Conclusions: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.     

Letter to the Editor

Abstract

Further correspondence on ‘Development of rapid heating and cooling (flash processing) process to produce advanced high strength steel microstructures’ by Lolla et al.     

The Interaction of Displaced Number State and Squeezed Number State Fields with Two-level Atoms

Abstract

The time-evolution of a single two-level atom in a single-mode high-Q cavity is sensitive to the quantum fluctuations of the cavity radiation field and to its photon statistics: this sensitivity is realizable experimentally in the Rydberg atom micromaser. We study the effects of the interaction of a two-level atom with two new non-classical radiation fields: the squeezed number state and the displaced number state realizable by nonlinear and linear transformations of field number states which have an initially precise occupation number. The time-varying field fluctuations caused by the atomic interaction are described using the Q-function quasi-probability.