Pathogenicity of the Transition m.3308T>C in Left Ventricular Hypertrabeculation/Noncompaction

No abstract available.     

Rituximab induced cytokine release syndrome in an MS patient: A case report

Cytokine release syndrome with rituximab has been reported in certain diseases, however, it is rarely reported in MS patients treated with rituximab. The treating physician should suspect the syndrome when typical signs and symptoms appear.     

Nano-based strategies to overcome p-glycoprotein-mediated drug resistance

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.

Areas covered: Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.

Expert opinion: Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.     

Augmentation of lymphocytes activation and T cell modulation by the extracts from some Euphorbia species

Context: Euphorbia is an important Euphorbiaceae genus that is traditionally being used for various infections, inflammation, and cancer.

Objective: The present study investigated the possible in vitro immunomodulatory effect of three species of Euphorbia genus including Euphorbia microciadia Boiss, Euphorbia osyridea Boiss, and Euphorbia heteradenia Jaub. &; Sp. on lymphocyte activation and cytokine secretion.

Materials and methods: Human lymphocytes were cultured in the presence of various concentrations (0.1–200?µg/ml) of the butanol/hexane extracts of the plants in the presence or absence of phytohemmagglutinin (PHA). The activation of lymphocytes after 48?h was determined by a proliferation assay. The release of T cell cytokines was studied to determine the dominant T cell subsets involved in the immune response.

Results: All three plant extracts increased the proliferation of PHA-treated lymphocytes (maximum; 132% of control). Extract treatment of lymphocytes in the absence of PHA resulted in an increased proliferation of the cells indicating their lymphocyte mitogenic activity (maximum at 10?µg/ml E. microciadia extract; 494.5?±?42.2% of control, p?E. microciadia and E. osyridea could increase IL-4 and IL-10 secretion but not IFN-γ production showing their capacity to deviate immune response toward a Th2 pattern. Euphorbia heteradenia did not change the release of IL-4 and IFN-γ cytokines but increased IL-10 production. The three extracts stimulated lymphocytes to produce IL-17 which showed their possible effects on Th17 cells activation.

Conclusion: The studied extracts had the ability to modulate T cell responses suggesting their possible beneficial effects on immune host defense.     

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

P2X7 receptors have been suggested to be located both on neurons and astrocytes of the central and peripheral nervous systems. In the present Ca²⁺-imaging and patch-clamp study, we reinvestigated these findings on mixed neuronal–astrocytic cell cultures prepared from embryonic or newborn rat hippocampi. We found in a Mg²⁺-free bath medium that the prototypic P2X7 receptor agonist dibenzoyl-adenosine triphosphate (Bz-ATP) increased the intracellular Ca²⁺ concentration ([Ca²⁺]_i) both in the neuronal cell bodies and in their axo-dendritic processes only to a very minor extent. However, Bz-ATP produced marked [Ca²⁺]_i transients in the neuronal processes, when they grew above a glial carpet, which was uniformly sensitive to Bz-ATP. These glial signals might be misinterpreted as neuronal responses because of the poor focal discrimination by a fluorescent microscope. Most astrocytes had a polygonal shape without clearly circumscribable boundaries, but a subgroup of them had neuron-like appearance. The cellular processes of this astrocytic subgroup, just as their cell somata and their polygonal counterparts, appeared to possess a high density of functional P2X7 receptors. In contrast to astrocytes, in a low Ca²⁺/no Mg²⁺-containing bath medium, hippocampal neurons failed to respond to Bz-ATP with membrane currents. In addition, neither the amplitude nor the frequency of spontaneous excitatory postsynaptic currents, representing the quantal release of glutamate, was modified by Bz-ATP. We conclude that cultured hippocampal neurons, in contrast to astrocytes, possess P2X7 receptors, if at all, only at a low density.     

The effects of DEX premedication on volatile induction of mask anesthesia (VIMA) and sevoflurane requirements

We investigated the effect of intravenous premedication with single dose of dexmedetomidine (DEX) on volatile anesthetic induction time and sevoflurane requirements of anesthesia maintenance in adults by monitoring the bispectral index (BIS). Sixty adult patients with status of ASA I–II undergoing general anesthesia with endotracheal intubation were randomly divided into two groups: The first group; a control group (group C, n = 30) and the second group; DEX group (group D, n = 30). Each patient in group D was premedicated with intravenous DEX 0.5 μg/kg or placebo 10 min before the induction of anesthesia. Anesthesia was induced by fentanyl 1 μg/kg, 1:1 ratio of nitrous oxide and oxygen and sevoflurane of 5–8 % and rocuronium bromur (Esmeron) 0.5 mg/kg keeping BIS values at 40–50. Time to induction of anesthesia, BIS, End-tidal sevoflurane concentration (Et_sevoflurane), End-tidal CO₂ concentration, duration of surgery, recovery time, hemodynamic variables, adverse effects were recorded intraoperatively. Analgesic requirement was noted in postoperative 24 h-period. The time to induction of anesthesia (p < 0.0001) and Et_sevoflurane at 1 min (p < 0.05) were significantly lower in group D than in group C. Intravenous premedication with 0.5 μg/kg of DEX decreased the induction time by almost 75 % and provided a significant decrease in Et_sevoflurane.