Steroidal spirooxetanes. I. Synthesis and antiandrogenic properties of some 17-spirooxetanoandrostanes

Pharmaceutical Chemistry Journal -     

Arylsulfatase A in urine of patients with urothelial tumors

A significant increase in urine arylsulfatase A activity (p less than 0.01) was found in patients with urothelial tumors. Arylsulfatase A activity was 1.36 +/- 1.10 U/24-h urine in control specimens, 1.90 +/- 1.66 U/24-h urine in various genitourinary tract disorders, and 3.90 +/- 1.98 U/24-h urine in transitional cell carcinoma specimens. Surgical treatment of the neoplastic patients lowered the arylsulfatase A activity found in urine to within reference values. The arylsulfatase A excreted by patients with these tumors was highly sensitive to thermal inactivation while the enzyme activity in the control urines was less affected by the heat treatment. The time course of the arylsulfatase A reaction with 4-nitrocatechol sulfate was not linear in normal individuals, while it was linear in 90% of patients with urothelial tumors. This difference in the kinetic pattern of the enzyme could be used to increase the diagnostic specificity of the determination.     

Macular thickness measurements using Copernicus Spectral Domain Optical Coherence Tomography

Purpose

To provide normal macular thickness measurements using Spectral Domain Optical Coherence Tomography (SDOCT, Copernicus, Optopol Technologies, Zawierci, Poland).

Methods

Fifty-eight eyes of 58 healthy subjects were included in this prospective study. All subjects had comprehensive ophthalmic examination including best-corrected visual acuity (BCVA). All the subjects underwent Copernicus SDOCT. Central foveal thickness (CFT) and photoreceptor layer (PRL) thickness were measured and expressed as mean and standard deviation. Mean retinal thickness for each of the 9 regions defined in the Early Treatment Diabetic Retinopathy Study was reported. The data were compared with published literature in Indians using Stratus and Spectralis OCTs to assess variation in instrument measurements.

Results

The mean CFT in the study sample was 173.8 ± 18.16 microns (131–215 microns) and the mean PRL thickness was 65.48 ± 4.23 microns (56–74 microns). No significant difference (p = 0.148) was found between CFT measured automated (179.28 ± 22 microns) and manually (173.83 ± 18.1 microns). CFT was significantly lower in women (167.62 ± 16.36 microns) compared to men (180.03 ± 18 microns) (p = 0.008). Mean retinal thickness reported in this study was significantly different from published literature using Stratus OCT and Spectralis OCT.

Conclusion

We report the normal mean retinal thickness in central 1 mm area to be between 138 and 242 microns in Indian population using Copernicus SDOCT. We suggest that different OCT instruments cannot be used interchangeably for the measurement of macular thickness as they vary in segmentation algorithms.     

A meta-analysis of amputation versus limb salvage in mangled lower limb injuries—The patient perspective

This meta-analysis evaluates the quality of life in post-traumatic amputees in comparison with limb salvage. Studies included in this meta-analysis had a minimum of 24 months of follow-up and used a validated quality-of-life outcome assessment scale (Short Form-36 or Sickness Impact Profile) for physical and psychological outcomes. Two reviewers performed the search and data extraction independent of each other.A total of 214 studies were identified; 11 fulfilled the inclusion criteria; thus, 1138 patients were available for meta-analysis (769 amputees and 369 cases of reconstruction).The meta-analysis demonstrated that lower limb reconstruction is more acceptable psychologically to patients with severe lower limb trauma compared with amputation, even though the physical outcome for both management pathways was more or less the same.     

Optimization of adenosine deaminase assay by response surface methodology

The effect of four variables (adenosine, glutamate dehydrogenase, phosphate buffer, and pH) on the measured catalytic concentration of adenosine deaminase (EC 3.5.4.4) was studied by Response Surface Methodology (RSM). This multivariate methodology offers an empirical approach to the study of enzyme assays and allows to detect the interaction between different variables of the system. Response–surface data showed maximum adenosine deaminase catalytic concentration at pH 7.2, adenosine 20 mmol/l, phosphate buffer 200 mmol/l and glutamate dehydrogenase 850 μkat/l when pleural fluids were used as samples. Optimum conditions for a material containing purified adenosine deaminase from human erythrocytes differed only slightly from that obtained for the pleural fluid.     

Colorimetry of diaphorase in commercial preparations and clinical chemical reagents by use of tetrazolium salts

We describe a procedure for assay of diaphorase activity in commercial purified preparations and in clinical chemical reagents by use of iodonitrotetrazolium chloride or other tetrazolium salts. The method is based on measurement of the formazan produced by enzymic reduction of tetrazolium salts in the presence of NADH. The assay procedure has been optimized for linear kinetics, simplicity of operation, nondetectable blank rates, and extended activity/enzyme concentration proportionality. The proposed method has several advantages over the older assay by use of dichlorophenolindophenol.     

Purification of human adenosine deaminase for the preparation of a reference material

The goal was to optimise a purification procedure of adenosine deaminase from human erythrocytes for the preparation of a European Reference Material. Adenosine deaminase was purified from human erythrocytes with a specific activity of 4.46 microkat/mg of protein and a catalytic concentration of 133 microkat/l. The isolation and purification procedure involved ion-exchange chromatography (STREAMLINE DEAE), and two purine riboside affinity chromatographies. The purified enzyme exhibits a single band in SDS-PAGE with a molecular weight of 41600 g/mol, and three bands in PAGE, isoelectric focusing and two-dimensional electrophoresis with pI 4.7, 4.85 and 5.0.     

Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus

It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD), but a mechanistic connection between both pathologies has not been provided so far. Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in the chronic complications of DM and have been reported to play an important role in the pathogenesis of AD. The earliest histopathological manifestation of AD is the apparition of extracellular aggregates of the amyloid β peptide (Aβ). To investigate possible correlations between AGEs and Aβ aggregates with both pathologies, we have performed an immuhistochemical study in human post-mortem samples of AD, AD with diabetes (ADD), diabetic and nondemented controls. ADD brains showed increased number of Aβ dense plaques and receptor for AGEs (RAGE)-positive and Tau-positive cells, higher AGEs levels and major microglial activation, compared to AD brain. Our results indicate that ADD patients present a significant increase of cell damage through a RAGE-dependent mechanism, suggesting that AGEs may promote the generation of an oxidative stress vicious cycle, which can explain the severe progression of patients with both pathologies.     

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase.

This paper is the fifth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 3.