Experimental Morphological Study of the Effects of Subchondral Tunnelization and Bone Marrow Stimulation on Articular Cartilage Regeneration

The articular cartilage was studied under conditions of experimental osteoarthrosis with tunnelization of the subchondral zone and injection of autologous bone marrow into the channels. Histomorphological studies showed that tunnelization of the subchondral zone with injection of autologous bone marrow into the channels stimulated reparative regeneration of the chondral tissue by inhibiting destruction of the joints.     

Slow isomerization step in the interaction between mouse dopamine transporter and dopamine re-uptake inhibitor N-(3-iodoprop-2E-enyl)-2beta-carbo-[3H]methoxy-3beta-(4'-methylphenyl)nortropane

The kinetics of the association and dissociation of the tritium-labeled selective and potent dopamine transporter inhibitor N-(3-iodoprop-2E-enyl)-2β-carbo-[³H]methoxy-3β-(4′-methylphenyl)nortropane ([³H]PE2I) with the transporter of mouse striatal membranes was studied. The analysis revealed that the specific binding of [³H]PE2I occurs within a homogeneous population of binding sites in these membranes. The relatively slow binding process was characterized by the pseudo-first-order rate constant k_obs. The plot of these rate constants versus free radioligand concentration was hyperbolic, demonstrating that at least two kinetically distinguishable steps can be identified in the interaction of dopamine transporter with this inhibitor. The fast and reversible binding step, characterized by dissociation constant K_A = 51 ± 23 nM, is followed by a slow but also reversible isomerization step of the complex, characterized by the isomerization rate constant k_i = (7 ± 2)10⁻² s⁻¹ and by the rate constant k_−i = (3.9 ± 0.5)10⁻³ s⁻¹ for the reverse process. This isomerization step increases the apparent affinity of the ligand and probably consists of a conformational transition of the transporter protein, induced by the inhibitor molecule.     

The diagnostic significance of laser 13C-urea breath test in various Helicobacter pylori-associated diseases

The authors present the results of laser-based 13C-urea breath test (13C-UBT) application in diagnostics of Helicobacter pylori-associated diseases (chronic gastritis, duodenitis, and peptic ulcer). 13C-UBT data distribution before and after eradication therapy, as well as age distribution, were obtained. Correlations between the nosological forms and the rate of contamination were established.     

Markers of structural and functional impairments of the central nervous system in an experimental model of thiopental coma

The markers of impairments of the nervous system were evaluated in rats at various time points after a sodium thiopental injection at the LD₅₀ using biochemical and immunohistochemical methods. The thiopental coma state was associated with a decrease in the levels of superoxide dismutase 6 h after the injection, glucose-6-phosphate dehydrogenase 24 and 72 h after the injection, and pigment epithelium-derived factor 6?2 h after the injection, as well an increase in the levels of glutathione peroxidase 72 h after the injection and caspase-3 6 h after the injection in the blood plasma of rats. Immunohistochemical study of caspase-3 in the brain tissue revealed increased expression of the enzyme in the sensorimotor cortex and hippocampus 3 days after the thiopental injection.     

Using Cholinesterases and Immobilized Luminescent Photobacteria for the Express-Analysis of Mycotoxins and Estimating the Efficiency of Their Enzymatic Hydrolysis

Novel sensitive analytical agents that can be used for simple, affordable, and rapid analysis of mycotoxins are urgently needed in scientific practice, especially for the screening of perspective bio-destructors of the toxic contaminants. We compared the characteristics of a rapid quantitative analysis of different mycotoxins (deoxynivalenol, ochratoxin A, patulin, sterigmatocystin, and zearalenone) using acetyl-, butyrylcholinesterases and photobacterial strains of luminescent cells in the current study. The best bioindicators in terms of sensitivity and working range (μg/mL) were determined as follows: Photobacterium sp. 17 cells for analysis of deoxynivalenol (0.8–89) and patulin (0.2–32); Photobacterium sp. 9.2 cells for analysis of ochratoxin A (0.4–72) and zearalenone (0.2–32); acetylcholinesterase for analysis of sterigmatocystin (0.12–219). The cells were found to be more sensitive than enzymes. The assayed strains of photobacterial cells ensured 44%–83% lower limit of detection for deoxynivalenol and sterigmatocystin as compared to the previously known data for immobilized luminescent cells, and the range of working concentrations was extended by a factor of 1.5–3.5. Calibration curves for the quantitative determination of patulin using immobilized photobacteria were presented in this work for the first time. This calibration was applied to estimate the enzyme efficiency for hydrolyzing mycotoxins using zearalenone and His₆-tagged organophosphorus hydrolase as examples.     

Dual tracer tau PET imaging reveals different molecular targets for <Superscript>11</Superscript>C-THK5351 and <Superscript>11</Superscript>C-PBB3 in the Alzheimer brain

Purpose

Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (¹¹C-THK5351 and ¹¹C-PBB3) in a head-to-head, in vivo, multimodal design.

Methods

Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers ¹¹C-THK5351 and ¹¹C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer ¹¹C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.

Results

The load and regional distribution of binding differed between ¹¹C-THK5351 and ¹¹C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of ¹¹C-PBB3, but not that of ¹¹C-THK5351, in the temporal lobe resembled that of ¹¹C-AZD2184, with strong correlations detected between ¹¹C-PBB3 and ¹¹C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with ¹¹C-THK5351 than with ¹¹C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with ¹¹C-THK5351 than with ¹¹C-PBB3 binding.

Conclusion

This research suggests different molecular targets for these tracers; while ¹¹C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of ¹¹C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.