Fear learning increases the number of polyribosomes associated with excitatory and inhibitory synapses in the barrel cortex

Associative fear learning, resulting from whisker stimulation paired with application of a mild electric shock to the tail in a classical conditioning paradigm, changes the motor behavior of mice and modifies the cortical functional representation of sensory receptors involved in the conditioning. It also induces the formation of new inhibitory synapses on double-synapse spines of the cognate barrel hollows. We studied density and distribution of polyribosomes, the putative structural markers of enhanced synaptic activation, following conditioning. By analyzing serial sections of the barrel cortex by electron microscopy and stereology, we found that the density of polyribosomes was significantly increased in dendrites of the barrel activated during conditioning. The results revealed fear learning-induced increase in the density of polyribosomes associated with both excitatory and inhibitory synapses located on dendritic spines (in both single- and double-synapse spines) and only with the inhibitory synapses located on dendritic shafts. This effect was accompanied by a significant increase in the postsynaptic density area of the excitatory synapses on single-synapse spines and of the inhibitory synapses on double-synapse spines containing polyribosomes. The present results show that associative fear learning not only induces inhibitory synaptogenesis, as demonstrated in the previous studies, but also stimulates local protein synthesis and produces modifications of the synapses that indicate their potentiation

Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells

ERK1/2 inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We found that VX-11e alone and in combination with voreloxin significantly decreased ERK activation in all cell lines tested. To evaluate the interactions of the drugs, cells were treated for 24 h with VX-11e or voreloxin alone and in combination at fixed ratios based on IC50 values. The combinatorial effects of both drugs were synergistic over a wide range of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were found to be additive, one antagonistic and only one synergistic. The results showed that incubation with both VX-11e and voreloxin inhibited the growth of leukemia cells, affected cell cycle and induced apoptosis. Furthermore, the molecular mechanism of these effects might be attributed to an increased expression of p21 and a decreased expression of survivin and NF-κB in all cell lines tested except from K562 cells. In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells

Effect of histone deacetylase inhibitors trichostatin A and valproic acid on etoposide-induced apoptosis in leukemia cells

Background: Histone deacetylase inhibitors (HDACi) have been extensively studied as potential candidates for treatment of various malignancies, including leukemia, since they not only induce growth inhibition, cell cycle arrest and apoptosis of cancer cells, but can also increase the sensitivity of cancer cells to chemotherapeutic drugs. The aim of this study was to investigate the effect of two HDACi, trichostatin A (TSA) and valproic acid (VPA), on etoposide-induced apoptosis in human leukemia cell lines. Materials and Methods: Viability, apoptosis rate, caspase activity, mitochondrial membrane potential and expression of BCL2 mRNA were assessed in HL60 and U937 cell lines treated with 250 nM TSA or 1.25 mM VPA alone or followed by 5 μM etoposide. Results: Preincubation of HL60 cells with TSA or VPA significantly potentiated etoposide-induced cytotoxicity and apoptosis, which was associated with activation of caspases and loss of mitochondrial membrane potential. Similar effects were not observed in U937 cells. Expression of BCL2 mRNA was strongly down-regulated after treatment of cells with HDACi alone but did not show additive effect with etoposide. Conclusion: Combination of HDACi with etoposide can have a synergistic effect on increased apoptosis in leukemia cells but this effect depends on the cancer cell type and other factors such as the concentration of drugs and the administration schedule

Fournier's gangrene – a clinical case report

Fournier’s gangrene is an acute, rapidly progressive, necrotizing infection of the skin and subcutaneous tissues surrounding the genitals and perineum. Necrotizing fasciitis of the genital area is a rare disease entity. Although it concerns mostly males, can also occur in females and adolescents. In this syndrome, bacteria produce gases which accumulate in the infected tissue. The damage may also comprise tissue of the penis and scrotum. The infection is caused by aerobic and anaerobic bacteria. Usually the Fournier’s gangrene is caused by Staphylococci, Streptococci and Enteric bacteria. Bacterial infection can accompany the fungal infection. The high mortality rate is associated with bacterial contagion of the skin, fat, fascia and blood vessels. Harmful enzymes, produced by micro-organisms, induce numerous blood clots. They can lead to ischemia, which contribute to the development of necrosis. Fournier’s syndrome is a disease with a high mortality rate. Immunodeficiency, diabetes and chronic alcohol abuse favor the development of gangrene. Abrasion, burn or surgery complication may be the route of infection for microorganisms. Clinical symptoms appear within few days. Diagnostic process is based on the clinical picture. It is crucial to start treatment as soon as possible. Delay of the wide spectral intravenous antibiotic therapy and surgical removal of the necrotic tissue may result in death of the patient

Correct human cardiac nomenclature

Proper heart’s nomenclature is very important in daily clinical practice and research studies, andwhen it is consistent, it can facilitate better communication between different medical specialists. Thegeneral rule of the anatomy is to describe organs and their structures in attitudinally correct position.However, the use of the old-fashioned Valentine position (where the heart is described as if it werestanding on its apex) is still in use to describe important cardiac structures. Upon closer analysis, all main chambers of the heart and their associated subcomponents have mislabeled structures that should be renamed. In this article we aimed to emphasize the limitations of Valentinian nomenclature, presentproper anatomical names of the most important heart’s structures and advocate to change certain mis-labeled anatomical structures. Attitudinally correct designations presented in this study will benefit allmedical specialties, and they will reinforce the importance of consistent orientational naming. Correctnaming of heart’s structures will also help improve communication between different medical specialists

Daily rhythm of synapse turnover in mouse somatosensory cortex

The whisker representations in the somatosensory barrel cortex of mice are modulated by sensory inputs associated with animal motor behavior which shows circadian rhythmicity. In a C57/BL mouse strain kept under a light/dark (LD 12:12) regime, we observed daily structural changes in the barrel cortex, correlated with the locomotor activity level. Stereological analysis of serial electron microscopic sections of the barrel cortex of mice sacrificed during their active or rest period, revealed an increase in the total numerical density of synapses and in the density of excitatory synapses located on dendritic spines during the rest, as well as an increase in the density of inhibitory synapses located on double-synapse spines during the active period. This is the first report demonstrating a daily rhythm in remodeling of the mammalian somatosensory cortex, manifested by changes in the density of synapses and dendritic spines. Moreover, we have found that the excitatory and inhibitory synapses are differently regulated during the day/night cycle