Diffusion changes in patients with systemic lupus erythematosus

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. METHODS: Data from 34 SLE patients (age range, 18-73 years) and 29 age-matched volunteers (age range, 29-64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (D(av)) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BD(av)). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. RESULTS: Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BD(av) and D(av) values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BD(av) and D(av) values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the D(av) values of the thalamus between the SLE patients and the control subjects. The BD(av) value in the SLE patient group was robustly correlated with the D(av) values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of D(av) and FA values in the SLE patient group. CONCLUSION: Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BD(av) and D(av) values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.     

Highly sensitive spectrophotometric methods for the determination, validation and thermogravimetric analysis of antiulcer drugs, nizatidine and ranitidine in pure and pharmaceutical preparations

Two sensitive, simple and rapid UV and second order derivative spectrophotometric methods were developed for the determination of nizatidine and ranitidine hydrochloride in pure form and pharmaceutical preparations. For the first method, UV spectrophotometic method, nizatidine was determined at 325 nm and ranitidine at 325.5 nm with detection limits of 0.07 and 0.04 μg/mL, respectively. For the second method, the distances between two extremum values (peak-to-peak amplitudes), 328/356.5 nm for nizatidine and 326/357 nm for ranitidine were measured in the second order derivative-spectra. The detection limits were found to be 0.02 μg/mL for nizatidine and 0.016 μg/mL for ranitidine, respectively. The thermal analysis of the two drugs was studied by Thermogravimetric Analysis-Differential Scanning Calorimetry (TGA-DSC) techniques. Enthalpy changes were obtained 121.9 and 124.15 J/g for nizatidine and ranitidine, respectively. The proposed method was successfully applied to the analysis of pharmaceutical preparations. The results were in good agreement with those obtained using the reference method; no significant difference were found in the accuracy and precision as revealed by the accepted values of t- and F-tests.     

Spectrofluorimetric Determination and Validation of Biotin in Pure and Dosage Form via Derivatization with 4-Fluoro-7-nitrobenzofurazan

A simple and highly sensitive spectrofluorimetric method was developed for the determination of biotin in pure and dosage form. The method is based on the derivatization of biotin with 4‐fluoro‐7‐nitrobenzofurazan in borate buffer of pH 9.0 to yield a yellow, fluorescent product. The various chemical conditions that affected the reaction were studied. The method was validated for specificity, linearity, precision, accuracy, recovery and robustness. At optimized experimental conditions, a linear relationship between the fluorescence intensity of the concentration of biotin is observed in the range 45–450 ng/mL. Limit of detection and quantification were 0.038 and 0.114 ng/mL, respectively. The percentage mean recovery was 99.96. The proposed procedure was successfully applied to the determination of biotin in its dosage form with mean recovery of 101.23±1.22 for biotin tablets. The results obtained were in good agreement with those obtained by the reference method.     

Møller Energy-Momentum Distribution of Higher Dimensional Vaidya Space-Time

In this paper, we intend to clarify the energy-momentum problem of higher dimensional Vaidya space-time in the general theory of relativity. In this connection, Møller energy and momentum for the higher dimensional Vaidya space-time are evaluated in the frame of general relativity. We have obtained that the Møller energy distribution of higher dimensional Vaidya space-time is equal to zero, while the Møller momentum distribution of higher dimensional Vaidya space-time is not equal to zero.     

Determination of Ciprofloxacin in Human Plasma and Urine by Precolumn Derivatization High Performance Liquid Chromatography with Fluorescence Detection

A sensitive, simple and selective high‐performance liquid chromatographic (HPLC) method was developed for the determination of ciprofloxacin in biological fluids. The method is based on the reaction between the drug and 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in borate buffer of pH 9.0 to yield a highly fluorescent derivative that is measured at 535 nm after excitation at 464 nm. The calibration curves were linear over the concentration ranges of 25–3000 and 50–3000 ng·mL^?1 for plasma and urine, respectively. The mean recovery of ciprofloxacin from plasma and urine was 98.37% and 98.40%, respectively. The method was found to be sensitive, precise, accurate, and reproducible. All of the validation parameters were within the acceptance range.     

Chloro-Modified Magnetic Fe3O4@MCM-41 Core–Shell Nanoparticles for L-Asparaginase Immobilization with Improved Catalytic Activity,Reusability, and Storage Stability

This paper describes a new support that permits to efficient immobilization of L-asparaginase (L-ASNase). For this purpose, Fe₃O₄ magnetic nanoparticles were synthesized and coated by MCM-41. 3-chloropropyltrimethoxysilane (CPTMS) was used as a surface modifying agent for covalent immobilization of L-ASNase on the magnetic nanoparticles. The chemical structure; thermal, morphological, and magnetic properties; chemical composition; and zeta potential value of Fe₃O₄@MCM-41-Cl were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential thermal analysis (DTA), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), scanning electron microscope (SEM), energy dispersive X-ray (EDX), X-ray diffraction patterns (XRD), and zeta-potential measurement. The immobilization efficiency onto Fe₃O₄@MCM-41-Cl was detected as 63%. The reusability, storage, pH, and thermal stabilities of the immobilized L-ASNase were investigated and compared to that of soluble one. The immobilized enzyme maintained 42.2% of its original activity after 18 cycles of reuse. Furthermore, it was more stable towards pH and temperature compared with soluble enzyme. The Michaelis–Menten kinetic properties of immobilized L-ASNase showed a lower V_max and a similar K_m compared to soluble L-ASNase. Immobilized enzyme had around 47 and 32.5% residual activity upon storage a period of 28 days at 4 and 25 °C, respectively. In conclusion, the Fe₃O₄@MCM-41-Cl@L-ASNase core–shell nanoparticles could successfully be used in industrial and medical applications.

     

LC Method with Precolumn Derivatization for Analysis of Mexiletine in Pharmaceutical Preparations

A isocratic, selective and accurate LC method of analysis of mexiletine in pharmaceutical preparations has been developed and validated. The method is based on derivatization of mexiletine with 4-chloro-7-nitrobenzofurazan in pH 9.0 borate buffer to yield a yellow product. Chromatography was performed on a C₁₈ column (150 × 4.6 mm i.d.) with acetonitrile–water 80:20 (v/v) as mobile phase at a flow rate of 1.0 mL min^?1. UV–visible absorbance detection was performed at 458 nm. The retention time of the mexiletine derivative was 4.10 min, and response was a linear function of concentration in the range 0.5–4.0 μg mL^?1 (r = 0.9998). The limits of detection and quantification were 0.05 and 0.15 μg mL^?1, respectively. Method validation revealed precision, sensitivity, and robustness were acceptable. Low RSD values are indicative of high precision, and high recovery values are indicative of the accuracy of the method. Results obtained by use of the proposed method for analysis of the mexiletine content of pharmaceutical a preparation were compared with those obtained by use of the official method. The method has been used for analysis of pharmaceutical preparations.     

Rapid and sensitive spectrofluorimetric determination of enrofloxacin, levofloxacin and ofloxacin with 2,3,5,6-tetrachloro-p-benzoquinone

A highly sensitive spectrofluorimetric method was developed for the first time, for the analysis of three fluoroquinolones (FQ) antibacterials, namely enrofloxacin (ENR), levofloxacin (LEV) and ofloxacin (OFL) in pharmaceutical preparations through charge transfer (CT) complex formation with 2,3,5,6-tetrachloro-p-benzoquinone (chloranil,CLA). At the optimum reaction conditions, the FQ–CLA complexes showed excitation maxima ranging from 359 to 363 nm and emission maxima ranging from 442 to 488 nm.Rectilinear calibration graphs were obtained in the concentration range of 50–1000, 50–1000 and 25–500 ng mL⁻¹ for ENR, LEV and OFL, respectively.The detection limit was found to be 17 ng mL⁻¹ for ENR, 17 ng mL⁻¹ for LEV, 8 ng mL⁻¹ for OFL, respectively. Excipients used as additive in commercial formulations did not interfere in the analysis. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The proposed method was successfully applied to the analysis of pharmaceutical preparations. The results obtained were in good agreement with those obtained using the official method; no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively.     

Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations

Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL(-1) for ciprofloxacin, 28.5-700 ng mL(-1) for enoxacin, 29.5-800 ng mL(-1) for norfloxacin and 33.5-1000 ng mL(-1) for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL(-1) for ciprofloxacin, 8.5 ng mL(-1) for enoxacin, 9.2 ng mL(-1) for norfloxacin and 9.98 ng mL(-1) for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method.     

Determination and Validation of an LC Method for Fluvoxamine in Tablets

A new, simple, rapid and specific reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the determination of fluvoxamine in pharmaceutical dosage forms. The HPLC separation was achieved on a C₁₈ μ-Bondapack column (250 mm × 4.6 mm) using a mobile phase of acetonitrile–water (80:20, v/v) at a flow rate of 1 mL min⁻¹. Proposed method is based on the derivatization of fluvoxamine with 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) in borate buffer of pH 8.5 to yield a orange product. The HPLC method is based on measurement of the derivatized product using UV-visible absorbance detection at 450 nm. The method was validated for specificity, linearity, precision, accuracy, robustness. The degree of linearity of the calibration curves, the percent recoveries of fluvoxamine, the limit of detection and quantification, for the HPLC method were determined. The assay was linear over the concentration range of 45–145 ng mL⁻¹ (r = 0.9999). Limit of detection and quantification for fluvoxamine were 15 and 50 ng mL⁻¹, respectively. The results of the developed procedure (proposed method) for fluvoxamine content in tablets were compared with those by the official method. The method was found to be simple, specific, precise, accurate, reproducible and robust.