Membrane properties and electrogenesis in the distal axons of small dorsal root ganglion neurons in vitro

Although it is generally thought that sensory transduction occurs at or close to peripheral nerve endings, with action potentials subsequently propagating along the axons of dorsal root ganglia (DRG) neurons toward the central nervous system, the small diameter of nociceptive axons and their endings have made it difficult to estimate their membrane properties and electrogenic characteristics. Even the resting potentials of nociceptive axons are unknown. In this study, we developed the capability to record directly with patch-clamp electrodes from the small-diameter distal axons of DRG neurons in vitro. We showed using current-clamp recordings that 1) these sensory axons have a resting potential of -60.2 ± 1 mV; 2) both tetrodotoxin (TTX)-sensitive (TTX-S) and TTX-resistant (TTX-R) Na(+) channels are present and available for activation at resting potential, at densities that can support action potential electrogenesis in these axons; 3) TTX-sensitive channels contribute to the amplification of small depolarizations that are subthreshold with respect to the action potential in these axons; 4) TTX-R channels can support the production of action potentials in these axons; and 5) these TTX-R channels can produce repetitive firing, even at depolarized membrane potentials where TTX-S channels are inactivated. Finally, using voltage-clamp recordings with an action potential as the command, we confirmed the presence of both TTX-S and TTX-R channels, which are activated sequentially during action potential in these axons. These results provide direct evidence for the presence of TTX-S and TTX-R Na(+) channels that are functionally available at resting potential and contribute to electrogenesis in small-diameter afferent axons.     

Effect of neuraminidase treatment on persistent epileptiform activity in the rat hippocampus

Negatively charged sialic acid residues located close to pores of voltage-gated sodium channels substantially influence their gating properties. The in vitro low Mg²⁺ seizure model is used to emulate difficult-to-treat status epilepticus. Using this model on cultured hippocampal slices, we examined the effectiveness of desialylation in reducing persistent seizure-like activity. We show that desialylation in cultured hippocampal slices effectively suppresses seizure-like activity induced by low Mg²⁺. These findings suggest that targeting negatively charged sialic acids may be an effective strategy to treat status epilepticus.     

Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates

The synthesis and antitumor activity screening of novel isatin based conjugates with thiazolidine and pyrazoline moieties were performed. Reaction of 3,5-diaryl-4,5-dihydropyrazoles with chloroacetyl chloride yielded starting 2-chloro-1-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-ethanones which were utilized in alkylation of isatin and 5-bromoisatin. Thus, corresponding 1-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-2-oxoethyl]-1H-indole-2,3-diones (1a-1d) have been obtained. The compounds 1a-1d have been used in Knoevenagel condensation with 4-thiazolidinones for obtaining a series of 5-ylidenederivatives 2a-2f and 3a-3d. The synthesized compounds were tested for their anticancer activity in NCI60 cell lines. Among the tested compounds, 5-bromo-1-{2-[5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-2-oxoethyl}-1H-indole-2,3-dione (1d) was found to be the most active candidate with selective influence on leukemia subpanel tumor cell lines with GI(50) values range of 0.69-3.35 μM.     

A facile synthesis and anticancer activity evaluation of spiro[thiazolidinone-isatin] conjugates

The synthesis and evaluation of the anticancer activity of 3'-aryl-5'-arylidene-spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-diones and spiro[3H-indole-3,2'-thi-azolidine]-2,4'(1H)-dione-3'-alkanoic acid esters were described. The structure of the compounds was determined by (1)H and (13)C NMR and their in vitro anticancer activity was tested in the National Cancer Institute. Among the tested compounds, (5'Z)-5'-(benzylidene)-3'-(4-chlorophenyl)spiro[3H-indole-3,2'-thia-zolidine]-2,4'(1H)-dione (IIa) and (5'Z)-3'-(4-chlorophenyl)-5'-[4-(1-methylethyl)-benzylidene]spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione (IIb) were superior to other related compounds.     

Systematic extended posterior right sectionectomy with simultaneous resection of the dorsal part of segment 1 and middle hepatic vein detachment

Parenchymal sparing surgery should be the strategy of choice for patients with bilobar liver metastases and lesions within the central liver sites.     

Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases

Purpose

The purpose of this study is to perform a retrospective analysis of types and frequencies of chromosomal abnormalities detected by conventional cytogenetic studies in first-trimester miscarriages after spontaneous conception and IVF.

Methods

Standard cytogenetic analysis of GTG-banded chromosomes obtained from products of conception (POCs): semi-direct and short-term cultured chorionic villi or long-term cultured fetal mesodermal cells.

Results

50.1% of first-trimester miscarriages in the studied group had chromosomal abnormalities: 59.7% of trisomies, 22% of poliploidies, 7.5% of monosomies, 7% of unbalanced structural abnormalities, and 3.8% of multiple aneuploidies. An increase in the frequency of chromosomally abnormal miscarriages was observed in the group of women above 40 when compared to groups of women under 35 (P < 0.05). No difference in frequencies and types of chromosomal abnormalities in POCs of miscarriages after ICSI and spontaneous conception was observed.

Conclusions

Approximately, 50% of first-trimester miscarriages have chromosomal abnormalities which can be detected by conventional cytogenetic analysis. The presence of chromosomal abnormality may explain the cause of miscarriage, improving the reproductive counseling and planning.

     

Role of cryopreserved multipotent mesenchymal stromal cells in modulation of some indices of cell immunity in adjuvant arthritis

InroductionThe results of experimental and clinical studies in recent years indicate that the transplantation of multipotent mesenchymal stromal cells (MMSCs) is a possible approach for the “restoration” of the immune system of patients with autoimmune diseases, in particular, rheumatoid arthritis. However, the strength and duration of the effect vary greatly, which indicates incomplete correction of the tested parameters, thereby opening up the prospect of improving this method of treatment by choosing dose-time parameters and methods of their administration. The aim of this research was to determine the indices of cellular immunity in animals with adjuvant arthritis and therapy with cryopreserved MMSCs derived from adipose and cartilage tissues.Material and methodsAdjuvant arthritis in male rats was modeled by subplantar administration of Freund’s complete adjuvant. On day 7 of modeling, experimental animals were administered with saline (control group) or cryopreserved MMSCs from adipose or cartilaginous tissue locally or generalized. On day 28 after therapy the body weight, spleen index and cellularity, and content of CD3+, CD4+, CD8+, CD4+CD25+ cells in the spleen were determined.ResultsIn the control group of animals, the inflammation was pronounced, as evidenced by a significant increase in the studied parameters throughout the observation period. The use of cryopreserved MMSCs from adipose and cartilaginous tissues led to the restoration of T regulatory cells (Treg) on day 28. Generalized administration of cells had a more pronounced therapeutic effect compared to the animals with local administration. These data can be used to justify and develop a therapeutic approach to rheumatoid arthritis in clinical practice.ConclusionsCell therapy with cryopreserved MMSCs from investigated sources provided by both local and generalized administration to animals with adjuvant arthritis has a correcting effect on the cellular immunity.     

Radiative and Magnetically Stimulated Evolution of Nanostructured Complexes in Silicon Surface Layers

The effect of a weak magnetic field (B = 0.17 T) and X-irradiation (D < 520 Gy) on the rearrangement of the defective structure of near-surface p-type silicon layers was studied. It was established that the effect of these external fields increases the positive accumulated charge in the region of spatial charge (RSC) and in the SiO₂ dielectric layer. This can be caused by both defects in the near-surface layer of the semiconductor and impurities contained in the dielectric layer, which can generate charge carriers. It was found that the near-surface layers of the barrier structures contain only one deep level in the silicon band gap, with an activation energy of Ev + 0.38 eV. This energy level corresponds to a complex of silicon interstitial atoms Si_I+Si_I. When X-irradiated with a dose of 520 Gy, a new level with the energy of Ev + 0.45 eV was observed. This level corresponds to a point boron radiation defect in the interstitial site (B_I). These two types of defect are effective in obtaining charge carriers, and cause deterioration of the rectifier properties of the silicon barrier structures. It was established that the silicon surface is quite active, and adsorbs organic atoms and molecules from the atmosphere, forming bonds. It was shown that the effect of a magnetic field causes the decay of adsorbed complexes at the Si–SiO₂ interface. The released hydrogen is captured by acceptor levels and, as a result, the concentration of more complex Si–H₃ complexes increases that of O₃–Si–H.     

Circulating C-Peptide Levels in Living Children and Young People and Pancreatic β-Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration

C-peptide declines in type 1 diabetes, although many long-duration patients retain low, but detectable levels. Histological analyses confirm that β-cells can remain following type 1 diabetes onset. We explored the trends observed in C-peptide decline in the UK Genetic Resource Investigating Diabetes (UK GRID) cohort (N = 4,079), with β-cell loss in pancreas donors from the network for Pancreatic Organ donors with Diabetes (nPOD) biobank and the Exeter Archival Diabetes Biobank (EADB) (combined N = 235), stratified by recently reported age at diagnosis endotypes (<7, 7–12, ≥13 years) across increasing diabetes durations. The proportion of individuals with detectable C-peptide declined beyond the first year after diagnosis, but this was most marked in the youngest age group (<1-year duration: age <7 years: 18 of 20 [90%], 7–12 years: 107 of 110 [97%], ≥13 years: 58 of 61 [95%] vs. 1–5 years postdiagnosis: <7 years: 172 of 522 [33%], 7–12 years: 604 of 995 [61%], ≥13 years: 225 of 289 [78%]). A similar profile was observed in β-cell loss, with those diagnosed at younger ages experiencing more rapid loss of islets containing insulin-positive (insulin+) β-cells <1 year postdiagnosis: age <7 years: 23 of 26 (88%), 7–12 years: 32 of 33 (97%), ≥13 years: 22 of 25 (88%) vs. 1–5 years postdiagnosis: <7 years: 1 of 12 (8.3%), 7–12 years: 7 of 13 (54%), ≥13 years: 7 of 8 (88%). These data should be considered in the planning and interpretation of intervention trials designed to promote β-cell retention and function.