Modulation of the NFAT signaling pathway by protein kinase B (PKB) ; a perspective study in the context of thymocyte development and T cell function

To analyze the role of protein kinase B(PKB)on developmental and functional aspects of T cells, we have generated transgenic mouse lines expressing a constitutively active form of PKB (myrPKB) in early stages of T cell development.Peripheral CD4+ T cells from PKB tg mice are hyperreactive, more efficient in producing th1 and th2 cytokines and show faster and CD28 co-stimulation independent cell cycle progression.Interestingly PKB tg T cells are resistant to CsA treatment in proliferation and cytokine production.Further analysis show PKB tg CD4+ T cells have a drastically reduced nuclear translocation of NFAT proteins and this is due to a direct interaction between PKB and NFAT. To study whether the negative regulatiopn of NFATs by PKB affects T cell development, we analyzed double tg mice expressing both, a constitutively active version of calcineurin (dCam) and myrPKB. dCam tg mice have a severe block in thymocyte development at the DN3 stage.But in the dCam/PKB double tg mice this developmental block is significantly rescued.This rescue of thymocyte development by PKB is due to the expression of RAG1 and subsequent TCRb chain expression. CsA treatment of neonatal thymic lobes from dCam mice restores normal thymocyte development, indicating involvement of NFATs in the severe block in dCam thymocyte development.Confocal studies clearly established that compared to dCam DN cells there is a significant reduction in the nuclear levels of NFATc1 and NFATc3 in dCam/PKB cells.Downregulation of nuclear NFAT levels by myrPKB thus seems to be an essential parameter in dCam cells to proceed with normal differentiation. In summary, the data from PKB tg peripheral CD4+ T cells and dCam/PKB double tg thymocytes clearly establish PKB as an important modulator of T cell development and function and PKB as a novel negative regulator of NFAT activation

Comparison between intravenous dexmedetomidine and midazolam for sedation during upper extremity surgeries under supraclavicular brachial plexus block

Background: The search for an ideal sedative agent during surgery under brachial plexus block still goes on. Midazolam is commonly used as a intraoperative sedative but it has no impact on brachial plexus block. Dexmedetomidine is a new alpha 2 receptor agonist used widely for sedation. Our aim was to compare the efficacy of  equivalent doses of dexmedetomidine infusion with midazolam  on sedation,block characteristics and patient satisfaction. Methods: In this study, 100 American Society of Anesthesiologists (ASA) I and II patients posted for forearm surgeries under ultrasound-guided brachial plexus block were divided to receive either midazolam (Group M) or dexmedetomidine (Group D) infusion. They were administered an initial loading dose of the midazolam and  dexmedetomidine over 10 min followed by a maintenance dose till the end of the surgery. Effect on sedation,block characteristics and patient satisfaction were monitored. P < 0.05 was considered statistically significant. Results: Time of onset of sedation was earlier in dexemedetomidine group compared to midazolam group. Profile of  block characteristics was better compared to midazolam group. Patient satisfaction score was greater in dexemedetomidine group compared to midazolam group.Conclusion: Dexmedetomidine may  be a better alternative to midazolam for sedation in patients undergoing surgeries in brachial plexus block

A case of Ewing’s sarcoma presenting with massive pleural effusion

A 16-year-old girl presented with swelling and heaviness on the right side of her chest and progressive dyspnoea since 20 days. Radiological examination revealed a mass lesion in the right lower zone with right-sided massive pleural effusion and rib erosion. Histopathology and immunohistochemistry were suggestive of Ewing’s sarcoma. We reported this case because of the uncommon presentation of this rare tumour and its associated pleural effusion. Early diagnosis of this case led to favourable outcomes

Interfacial and Aggregation Behavior of Dicarboxylic Amino Acid-Based Surfactants in Combination with a Cationic Surfactant

The interfacial and micellization behavior of three dicarboxylic amino acid-based anionic surfactants, abbreviated as AAS (N-dodecyl derivative of -aminomalonate, -aspartate, and -glutamate) in combination with hexadecyltrimethylammonium bromide (HTAB) were investigated by surface tension, conductance, UV-vis absorption/emission spectroscopy, dynamic light scattering (DLS), and viscosity studies. Critical micelle concentration (CMC) values of the surfactant mixtures are significantly lower than the predicted values, indicating associative interaction between the components. Surface excess, limiting molecular area, surface pressure at the CMC, and Gibbs free energy indicate spontaneity of the micellization processes compared to the pure components. CMC values were also determined from the sigmoidal variation in the plot of micellar polarity and pyrene UV vis absorption/emission intensities with surfactant concentration. The aggregation number, determined by static fluorescence quenching method, increases with decreasing mole fraction of the AAS (alpha(AAS)), where the micelles are mainly dominated by the HTAB molecules. The size of the micelle increases with decreasing alpha(AAs), leading to the formation of larger and complex aggregates, as also supported by the viscosity studies. Micelles comprising 20-40 mol % AAS are highly viscous, in consonance with their sizes. Some of the mixed surfactant systems show unusual viscosity (shear thickening and increased viscosity with increasing temperature). Such mixed surfactant systems are considered to have potential in gel-based drug delivery and nanoparticle synthesis

Micro-structural investigations on oppositely charged mixed surfactant gels with potential dermal applications

Dicarboxylic amino acid-based surfactants (N-dodecyl derivatives of -aminomalonate, -aspartate, and -glutamate) in combination with hexadecyltrimethylammonium bromide (HTAB) form a variety of aggregates. Composition and concentration-dependent mixtures exhibit liquid crystal, gel, precipitate, and clear isotropic phases. Liquid crystalline patterns, formed by surfactant mixtures, were identified by polarizing optical microscopy. FE-SEM studies reveal the existence of surface morphologies of different mixed aggregates. Phase transition and associated weight loss were found to depend on the composition where thermotropic behaviours were revealed through combined differential scanning calorimetry and thermogravimetric studies. Systems comprising more than 60 mol% HTAB demonstrate shear-thinning behaviour. Gels cause insignificant toxicity to human peripheral lymphocytes and irritation to bare mouse skin; they do not display the symptoms of cutaneous irritation, neutrophilic invasion, and inflammation (erythema, edema, and skin thinning) as evidenced by cumulative irritancy index score. Gels also exhibit substantial antibacterial effects on Staphylococcus aureus, a potent causative agent of skin and soft tissue infections, suggesting its possible application as a vehicle for topical dermatological drug delivery.Validerad;2021;Nivå 2;2021-08-17 (alebob);Forskningsfinansiär: University Grants Commission (F.25-1/2014-15(BSR)/7-234/2009(BSR); F. 5-9/2015/DRS-II (SAP-II)); Department of Science and Technology, Govt. of India (SR/FST/CS-I/2017/7 (C))</p