Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4+ Valpha24 natural killer T cells expressing CD40L

Human Valpha24 natural killer T (Valpha24NKT) cells are activated by alpha-glycosylceramide-pulsed dendritic cells (DCs) in a CD1d-dependent and T-cell receptor-mediated manner. There are two major subpopulations of Valpha24NKT cells, CD4- CD8- Valpha24NKT and CD4+ Valpha24NKT cells. We have recently shown that activated CD4- CD8- Valpha24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of Valpha24NKT cells is currently limited. We aimed to investigate whether CD4+ Valpha24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4+ Valpha24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4+ Valpha24NKT cells, but not with resting CD4+ Valpha24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb. Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40-CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Valpha24NKT cells. The apoptosis of DCs from normal donors, triggered by the CD40-CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4+ Valpha24NKT cells by virtue of apoptosis of DCs.     

Study of neurotrophic effects of yashaltin mud in experimental model of denervation-reinnervation syndrome of shank muscles in mice

On the experimental model of denervation-reinnervation syndrome of mouse shank muscles neurotrophic effects of jashaltinsky medicinal mud were studied. In experimental mice therapeutic mud has been applied on the small back, tail and rib areas of the body 10 days after nerve crushing. On day 11 after nerve crushing a stable reproduction of a compound nerve action potential with constant amplitude was revealed in repetitive (50 Hz) nerve stimulation.     

Corrosion Resistance of Al–CNT Metal Matrix Composites

The design of aluminium–graphite metal matrix composites (MMCs) with advanced mechanical properties and high corrosion resistance is in demand for aerospace, transportation, and industrial applications. Breakthroughs in this field are limited due to the tendency of aluminium–graphite MMCs to corrode. In the present research, aluminium-based MMCs were produced by a relatively novel combined two-staged method. Multiwall carbon nanotubes (MWCNTs) were added into molten Al1070 and processed by high-pressure die casting followed by cyclic extrusion. For the composites produced by this method, it was previously demonstrated that mechanical properties are improved in comparison with pure aluminium alloys. In the current study, the manufactured Al–MWCNT composites were investigated by electrochemical tests (such as open circuit potential), potentiodynamic tests, linear polarization tests, and electrochemical impedance spectra to understand the corrosion resistance of the obtained composite material. The experimental testing of the corrosion resistance of Al–MWCNT MMCs showed that due to the advantages of the fabrication method, the addition of CNTs to aluminium does not cause a radical decrease of corrosion resistance.     

Characterization of novel Mycobacterium tuberculosis pncA gene mutations in clinical isolates from the Ukraine

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis cases in the Ukraine are increasing. Pyrazinamide (PZA) is critically important for first- and second-line tuberculosis (TB) treatment regimes. However, PZA drug susceptibility testing is time consuming and technically challenging. The present study utilized Next-generation sequencing (NGS) to identify mutations in the pncA gene from clinical isolates and to assess the prevalence of pncA gene mutations in MDR/XDR-TB patients. Clinical isolates were inactivated in molecular transport media and shipped from Kharkiv, Ukraine, to San Antonio, TX. Whole-genome and targeted pncA gene sequencing was carried out using Illumina MiSeq instrumentation. Mutations were noted in 67 of 91 (74%) clinical isolates comprising substitutions, insertions, and deletions in the pncA coding and upstream promoter region. Of 45 mutation types, there were 11 novel, i.e., to date unknown, pncA mutations identified of which 3 were confirmed PZA resistant. Seven isolates contained mixed base mutations, whereas 4 harbored doubled mutations. Data reported here further support use of NGS for pncA gene characterization and may contribute in significant fashion to PZA therapy, especially in MDR- and XDR-TB patients.     

Drug-induced sweat gland necrosis in a non-comatose patient: a case presentation

BACKGROUND: Coma-induced bullae and sweat gland necrosis is a rare clinicopathological entity often associated with drug-induced coma. SUBJECT: We report a case with clinical and histopathologic findings characteristic of blisters and sweat gland necrosis occurring in a non-comatose patient. CONCLUSIONS: Skin blisters with underlying sweat gland necrosis is an entity previously reported to occur in comatose patients, our findings open new questions about the role of the drugs in the pathogenesis of those conditions.     

Digoxin facilitates neuromuscular transmission in mouse diaphragm

Low concentration of digoxin (3 nM) facilitated spontaneous and evoked release of neurotransmitter acetylcholine thereby increasing the frequency of miniature end-plate potentials, amplitude of single end-plate potentials, their quantum content and the plateau level in the bursts during stimulation of the phrenic nerve at rates of 4, 7, and 50 Hz. These effects were prevented by blockade of ryanodine receptors with ryanodine (10–20 μM). __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 10, pp. 364–368, October, 2007