Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.

A Sensitive Reversed-Phase High-Performance Liquid Chromatography Method for the Quantitative Determination of Milk Xanthine Oxidase Activity

A new reversed-phase high performance liquid chromatography method was developed to quantitate the activity of xanthine oxidase involved in milk fat globule membrane with xanthine as the substrate and the separation of product (uric acid). The increment of uric acid in the reaction system was used to calculate the total activity of XO. The optimized assay conditions, linearity of detection, recovery of uric acid and chromatogram were developed in text, indicating this method is simple, rapid and efficient. It is an alternative potential method for the determination of the activity of XO in milk.

Simultaneous Determination of Amlodipine with H₁-Receptor Antagonists by Reversed Phase High Performance Liquid Chromatography and Application to Interaction Studies

A rapid, fast and precise method has been developed and validated for the simultaneous determination of amlodipine with H1-receptor antagonists (cetirizine, fexofenadine, and buclizine) from dosage forms. The chromatography was performed on a Purospher? Star, C18 (5 mm, 250 × 4.6 mm) column using acetonitrile: buffer (0.01 mM) (40:60, v/v, pH adjusted to 3.0), as a mobile phase. The mobile phase was pumped at a flow rate of 1.0 mL·min-1 and UV detection was performed at 240 nm. The method was validated for linearity, accuracy, precision and specificity. The method was applied to study the interaction between amlodipine and H1-receptor antagonists. These interactions were carried out in simulated gastric juice (pH 1), simulated full stomach (pH 4), blood pH (pH 7.4) and simulating GI (pH 9). The interacting drugs were heated at 37℃ with intermit-tent shaking and the samples were withdrawn every thirty minutes for three hours and drug contents were analyzed by RP-HPLC techniques. In most cases the in vitro availability of amlodipine was decreased. It was observed that the change in in vitro availability was pH dependent.

Creation of reversed phase high-performance liquid chromatographic technique to assay platelet-activating factor

Objective: To establish a new assay for platelet-activating factor (PAF), to compare it with bio-assay; and to discuss its significance in some elderly people diseases such as cerebral infarction and coronary heart disease. Methods: To measure PAF levels in 100 controls, 23 elderly patients with cerebral infarction and 65 cases with coronary heart disease by reversed phase high-performance liquid chromatographic technique (rHPLC). Results:rHPLC is more convenient, sensitive,specific, and less confusing, compared with bio-assay. The level of plasma PAF in patients with cerebral infarction was higher than that in the controls (P<0.01), and in patients with coronary heart disease. Conclusion: Detection of PAF with rHPLC is more reliable and more accurate. The new assay has important significance in PAF research.

Quantitative analysis by reversed-phase high-performance liquid chromatography and retinal neuroprotection after topical administration of moxonidine

AIM:To determine moxonidine in aqueous humor and iris-ciliary body by reversed-phase high performance liquid chromatography(RP-HPLC),and to evaluate the retinal neuroprotective effect after topical administration with moxonidine in a high intraocular pressure(IOP)model.METHODS:The eyes of albino rabbits were administered topically and ipsilaterally with 0.2%moxonidine.A RPHPLC method was employed for the identification and quantification of moxonidine between 2 and 480 min,which presented in the aqueous humor and iris-ciliary body.Flash electroretinography(F-ERG)amplitude and superoxide dismutase(SOD)level were measured between day 1 and day 15 after topical administration with moxonidine in a rabbit model of high IOP.Histological and ultrastructural observation underwent to analyze the changes of retinal morphology,the inner retinal layers(IRL)thickness,and retinal ganglion cell(RGC)counting.RESULTS:Moxonidine was detectable between 2 and 480 min after administration,and the peak concentration developed both in the two tissues at 30 min,0.51μg/m Lin aqueous humor and 1.03μg/g in iris-ciliary body.In comparison to control,F-ERG b-wave amplitude in moxonidine eyes were significantly differences between day 3 and day 15(P<0.01)in the high IOP model;SOD levels were significantly higher at all time-points(P<0.01)with a maximum level of 20.29 U/mgprot at day 15;and RGCs were significantly higher(P<0.05).CONCLUSION:Moxonidine is a viable neuroprotective agent with application to high IOP model.All layers of retina,including RGC layer,retinal nerve fiber layer and INL,are more preserved after moxonidine administration.SOD plays a neuroprotective role in ocular hypertension-mediated RGC death.

Actional Mechanism of Trifluoroacetic Acid for the Separation of Biopolymers by Reversed-phase Liquid Chromatography

The present paper covers the actional mechanism of trifluoroacetic acid for the separation of biopolymers investigated by using the parameters of stoichiometric displacement model for retention(SDM-R) in reversed-phase liquid chromatography. It was found that the trifluoroacetic acid(TFA) may participate in, or stimulate the association among displacing agent molecules in mobile phase, and decrease the affinity of both the associate molecules of the displacing agent and the TFA-protein ion-pairing. The former dominates over the separation selectivity of biopolymers as the concentration of TFA is lower than a given value, and the two contrary functions partly offset to each other and the latter dominates as its concentration is greater than the given value.

Reversed-Phase HPLC Analysis of Steviol Glycosides Isolated from Stevia rebaudiana Bertoni

High Performance Liquid Chromatography (HPLC) experiments have been performed on nine steviol glycosides namely rebaudioside A, steviolbioside, stevioside, rubusoside, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside F, and dulcoside A isolated from the leaves of Stevia rebaudiana using Reversed-Phase (RP) column. Using RP-HPLC method, the individual retention times for nine naturally occurring ent-kaurane diterpene glycosides of S. rebaudiana reported in JECFA have been determined at four different temperatures: 20℃, 40℃, 60℃, and 79℃. Also, calculated the relative retention times of the eight steviol glycosides steviolbioside, stevioside, rubusoside, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside F, and dulcoside A against the major steviol glycoside rebaudioside A. HPLC results suggested that temperatures 40℃ and 60℃ would be ideal conditions for better separation of steviol glycosides.

Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

Determination of isotretinoin in pharmaceutical formulations by reversed-phase HPLC

The development of facile and rapid quantification of biologically active biomolecules such as isotretitoin in therapeutic drugs contained in many generic formu- lations is necessary for determining their efficiency and their quality to improve the human health care. Isotretritoin finds its applications in the maintenance of epithelial tissues. Different processes to date such as normal phase HPLC, or gas chromatrography am- ong others are able to separate and quantify isote- troin. However, the extraction is quite complex and in the case of HPLC, the analysis requires long retention times. In such context, an isocratic reversed- phase high-performance liquid chromatography (HP- LC) technique coupled with an UV-vis detector is described here for easy separation and quantification of 13-cis-retinoic (isotretinoin) from soft gelatin capsule formulations. The isotretinoin was extracted from three different commercial drug samples with tetrahydrofuran (THF) solvent by a procedure that can be completed in less than 10 minutes. Subsequent separation and quantification were accomplished in less than 5 minutes under isocratic reversed-phase conditions on a Lichrospher RP18 column and a mobile phase consisting of 0.01% TFA/acetonitrile (15/85, v/v) at a flow rate of 1.0 mL/min. Isotretoin was detected for the three samples via its UV-vis absorbance at 342 nm. The method was validated and the results showed good linearity, precision and accuracy for sensitive and selective quantitative determination of isotretinoin in the different pharmaceutical formulations. We found that the average isotretinoin content in two of the three commercial pro- ducts fell outside the 90-110% United States Pha- rmacopeia specifications. Consequently, the facile extraction and the precise method for the biomole- cule quantification open up tremendous possibilities in improving the quality control of drugs which can exist as different generic brands.

Dynamic phase assembled terahertz metalens for reversible conversion between linear polarization and arbitrary circular polarization

If a metalens integrates the circular polarization(CP)conversion function,the focusing lens together with circular-polariz-ing lens(CPL)in traditional cameras may be replaced by a metalens.However,in terahertz(THz)band,the reported metalenses still do not obtain the perfect and strict single-handed CP,because they were constructed via Pancharatnam-Berry phase so that CP conversion contained both left-handed CP(LCP)and right-handed CP(RCP)components.In this paper,a silicon based THz metalens is constructed using dynamic phase to obtain single-handed CP conversion.Also,we can rotate the whole metalens at a certain angle to control the conversion of multi-polarization states,which can simply manipulate the focusing for incident linear polarization(LP)THz wave in three polarization conversion states,in-cluding LP without conversion,LCP and RCP.Moreover,the polarization conversion behavior is reversible,that is,the THz metalens can convert not only the LP into arbitrary single-handed CP,but also the LCP and RCP into two perpen-dicular LP,respectively.The metalens is expected to be used in advanced THz camera,as a great candidate for tradi-tional CPL and focusing lens group,and also shows potential application in polarization imaging with discriminating LCP and RCP.

Novel guanidinium-based ionic liquids as stationary phases for capillary gas chromatography

The present study describes guanidinium-based ionic liquids（GBILs） as stationary phases for capillary gas chromatography （CGC） and to the best of our knowledge,no related reports are available up to now.In this study,a hexaalkylguanidinium ionic liquid（DOTMG-NTf;） was synthesized and coated statically onto capillary columns.Selectivity of the stationary phase was evaluated by separating Grob test mixture,test mixture,alcohols mixture,and fatty acid methyl esters mixture,and thermal stability was investigated as well.The present study demonstrates that GBILs as CGC stationary phases exhibit satisfactory selectivity and thermal stability and have a great potential as new candidates for CGC stationary phases.

Preparation of new hybrid organic/inorganic polymeric chiral stationary phases for ligand-exchange chromatography

Three new hybrid organic/inorganic polymeric ligand-exchange chiral stationary phases were developed by radical chain transfer reaction and surface grafting on silica gel, and successfully used for the enantioseparations of DL-amino acids and DL-hydroxyl adds. The resolutions were achieved by using water containing 2.0 × 10^-4 mol/L of CuAc2 as a mobile phase, column temperature of 40 ℃, flow rate of 1.0 mL/min and detection at UV 254 nm. The elution order of D-isomer before L-isomer was observed for all DL-amino acids resolved except DL-Pro.

Retention behaviors of novel ionic liquid stationary phases and their selectivity for capillary gas chromatography

One chloride-terminated ionic liquid（CTIL） and two hydroxyl-terminated ionic liquids（HTILs） were synthesized and used as stationary phases for capillary gas chromatography（CGC）.Molecular interactions of these stationary phases were evaluated by Abraham solvation parameter model,indicating that the CTIL exhibits remarkably strong H-bond basicity and the HTILs possess both H-bond basicity and acidity.The molecular interactions were further confirmed by separation of a complex mixture consisting of ketones,aldehydes,esters,alcohols and aromatic compounds.It was found that the obtained solvation parameters correlate well with the chromatographic performances of the analytes in terms of elution order and resolution.The well correlated relationship between the solvation parameters and the selectivity of the CTIL and HTILs stationary phases is quite helpful in predicting and understanding the retention behaviors of different types of analytes on these stationary phases.

Separation of Enantiomers of Clopidogrel on Chiral Stationary Phases by Packed Column Supercritical Fluid Chromatography

A packed column supercritical fluid chromatography (SFC) method for the separation of clopidogrel enantiomers on a chiral stationary phase and CO2 with modifier as mobile phase has been developed at an analytical scale. Among 11 different 2 stationary phases the Chiral cel OD-H column showed by far the best separation properties. The influence of different modifiers, injection solvents, temperature, and pressure, and density of the fluid, respectively, on the separation behaviour has been studied. It was found that the separation behaviour strongly depends on the type of modifier and the modifier content. Temperature and pressure are of less influence.

Rapid analysis of fifteen sulfonamide residues in pork and fish samples by automated on-line solid phase extraction coupled to liquid chromatography–tandem mass spectrometry

The aim of this work was to develop an automated on-line solid phase extraction(SPE)with liquid chromatography-tandem mass spectrometry method for the detection of fifteen sulfonamides in pork and fish samples.Samples were extracted with 0.2%formic acid acetonitrile solution,purified by on-line SPE device with HLB column,then separated by XBridge C18 column,using 0.1%formic acid solution and acetonitrile as the mobile phase.Mass spectrometric data was acquired under multiple reaction monitoring(MRM)mode using positive ionization electrospray.Internal standard method was used in the quantification,good linear relationship was got in range of 0.1–100 ng/mL and correlation coefficient was higher than 0.9990.The limits of detection were in the range of 0.125–2.00g/kg and the limits of quantitation were in the range of 0.250–5.00g/kg.Recoveries of the method were in range of 78.3%–99.3%,relative standard deviation were lower than 10%.The method was simple,sensitivity,and could be used for routine supervision and analysis of fifteen sulfonamides in pork and fish.

Development of a Rapid and Efficient Liquid Chromatography Method for Determination of Gibberellin A4 in Plant Tissue, with Solid Phase Extraction for Purification and Quantification

A new, rapid and efficient reverse phase Liquid Chromatography (RP-LC) method was developed for determination of Gibberellin A4 (GA4) in samples of flower stalk of Dasylirion cedrosanum and vegetative tissue of Epithelantha micromeris. Purification of GA4 was carried out by solid phase extraction (SPE), in Epithelantha micromeris. In the chromatography method was obtaining a retention time of 2.1 min, using Hypersil GOLD C-18 column (100 × 4.6 mm dim and size particle 5 μ), mobile phase 50/50 acetonitrile/water and a flow 1.0 ml/min. Detection was carried out by a UV detector set at 205 nm, and a quantization limit of 0.4 mg/L. The obtained correlation coefficient was 0.995.

Modification of Chiral Stationary Phases with L-Proline as a Selector for Ligand-exchange Chromatography via Introducing Hydrophobic Groups

Three chiral stationary phases（CSPl, CSP2 and CSP3） for ligand-exchange chromatography were prepared by firstly using dimethylchlorosilane as an endcapping reagent for decreasing residual silanol groups on the surface of silica gel, and then modifying the surface of silica gel with allyl glycidyl ether and alkenes through the hydrosilation reaction, and lastly introducing L-proline as a chiral selector. The enantiomer resolutions of 14 amino acids and 2 hydroxyl acids were completed on the CSPs by using an aqueous solution of Cu（Ac）2 as mobile phase at a flow rate of 1.0 mL/min and column temperature of 40 ℃ with detection at UV 254 nm. In terms of enantioseleetivity a, column efficiency and resolution Rs, the chromatographic behaviors of the analytes on the CSPs were discussed via comparing them to those on the CSP4 prepared via the reference method. The results show that enantioselectivity a, column efficiency and resolution Rs of the analytes on the CSPs could be improved by using the above modifying method.

Reverse Transformation Behavior of TiNi Shape Memory Alloys Prestrained in the Parent Phase

The reverse martensitic transformation of TiNi alloy wires prestrained in the parent phase was studied. Experimental results shou, that the reverse transformation of the TiNi allogys prestrained in the parent phase is significantly different from that of the TiNi alloys prestrained in the martensite phase. Three continual peaks appear on the DSC curves of wires with a small prestrain and one high temperature peak appears on the DSC curves of wires with a large prestrain.

Uncertainty Evaluation of Determination of Microcystin MC-LR in Environmental Samples by Solid Phase Extraction-Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

To assess uncertainty of determination of MC-LR in environmental samples by solid phase extraction- ultra performance liquid chromatography- tandem mass spectrometry,the sources of the uncertainty were evaluated firstly,and the expanded uncertainty was calculated finally.The results show that when MC-LR concentration in the water samples was 0.50 μg/L,the expanded uncertainty was 0.00628 μg/L(k=2).

Synergistic Effect in Mixed Capillary Gas Chromatographic Stationap Phases Containing Heptakis(2,3,6-tri-o-pentyl)-β-cyclodextrin and Dibenzo-18-crown-6

used－silical capillary columns containing heptakis（2、3、6－tri－o－pentyl）-β-cyclodextrinand dibenzo-18-crown-6 were prepared．By studying the selectivity of mixed stationary phases forsome solute pairs.as well as comparing with the heptakis（2．3、6-tri-O-pentyl）-β-cyclodextrin and thedibenzo-18-crown-6 used as individual stationary phase、the synergistic effects were observed.These effects were affected by the column temperature．mixed ratio and linear velocity of carrier gas．