L-Ascorbic Acid and α-Tocopherol Reduces Hepatotoxicity Associated with Arsenic Trioxide Chemotherapy by Modulating Nrf2 and Bcl2 Transcription Factors in Chang liver Cells

Arsenic trioxide (As₂O₃) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind As₂O₃ toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and α-TOC against As₂O₃ toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 µM) and α-TOC (50 µM) recovered As₂O₃ (10 µM) cytotoxicity. Furthermore, As₂O₃ treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with As₂O₃ resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression.     

In vitro selection of self-cleaving RNAs with a low pH optimum

RNAs that undergo a rapid site-specific cleavage at low pH have been selected by in vitro selection (the SELEX process). The cleavage does not require the addition of any divalent metal ions, and is in fact inhibited by divalent metal ions, spermine, or high concentrations of monovalent metal ions. This low pH catalyzed cleavage results in a 2′,3′-cyclic phosphate at the 3′ end and a free hydroxyl at the 5′ end. The reaction proceeds with a calculated rate of 1.1 min⁻¹ at room temperature in cacodylate buffer at pH 5.0. The rate of cleavage is dependent on the pH and shows an optimum around pH 4.0. The rate constant is independent of RNA concentration, indicating to an intramolecular reaction. Autocatalytic cleavage at low pH, in the absence of a metal ion requirement, adds to the reaction possibilities that may have existed on the prebiotic earth.     

Recurrent hyperhemolytic transfusion reaction in myelodysplastic syndrome- A case based approach

We present here a case report of a 27 year old female, with myelodysplatic syndrome suspected to have recurrent hyperhemolytic transfusion reactions (HHTR). Patient was transfusion dependent for ten years and was transfused with leukodepleted and irradiated Packed Red Blood Cells (PRBC). She presented with signs and symptoms of acute intravascular hemolysis, deranged coagulation profile with post transfusion Hb lower than baseline. Post transfusion workup was uneventful. She was managed conservatively with fluid support and methylprednisolone initially. After few uneventful transfusions, patient developed second episode of HHTR with compatible unit.Immunophenotype favored an inflammatory response possibly induced by monocytic lineage. As transfusion dependent, the patient required methylprednisolone as premedication and all subsequent transfusions were uneventful.     

First Hour Initiation of Breastfeeding and Exclusive Breastfeeding at Six Weeks: Prevalence and Predictors in a Tertiary Care Setting

Objective

To assess the prevalence of first hour breastfeeding initiation and exclusive breastfeeding at 6 wk and identify its barriers in healthy term babies born in a tertiary hospital setting.

Methods

A prospective observational cohort study was carried out in consecutively selected 400 mothers who delivered (normal, instrumental or cesarean) term healthy babies in a tertiary care hospital setting. All mother-infant dyads were enroled within 48 h of delivery.

Results

Breastfeeding was initiated within first hour in 255 out of 400, i.e., 64 % of babies. Cesarean delivery and male gender were strongest risk factors for delayed initiation of breastfeeding [OR (95 % CI)?=?1.99 (1.14–3.48) and 34.17 (17.10–70.40) respectively]. Among the babies followed up till 6–8 wk, 83 % were exclusively breastfed. Breast milk substitutes were given in 172/400 (43 %) babies on day one, which emerged as an independent predictor of failure to continue exclusive breastfeeding at 6 wk (OR 2.96; 95 % CI 1.09–8.06). Odds of exclusive breastfeeding were two times higher in babies breastfed within first hour (n?=?255/400, 64 %) when compared to babies initiated breastfeeds beyond first hour (n?=?145/400, 36 %) (OR 2.01;05 % CI 1.12–3.61).

Conclusions

Cesarean section and male gender emerged as significant risk factors for delayed initiation (beyond first hour) of breastfeeding in the index study cohort. In addition, use of breast milk substitute emerged as the only predictor for failure to continue exclusive breastfeeding at six weeks in a tertiary care hospital.     

Imaging of the adult male urethra,penile prostheses and artificial urinary sphincters

Abdominal Radiology - To discuss the imaging appearances of various pathologies affecting adult male urethra and to review the role of imaging in the assessment of artificial urinary sphincters and...     

Capitalizing on technology for developing communication skills in autism spectrum disorder: a single case study

Purpose: In this case study, we discuss the application of a patient-centred clinical approach that led to the use of an assisted communication platform to combat severe communicative deficit in a child with autism spectrum disorder (ASD).

Methods: Initial assessment at four years of age revealed that the patient had rudimentary communication skills, with significant sensory integration dysfunction manifested as oral, olfactory, and tactile seeking behaviours; self-stimulatory behaviour; and complete dependence on caregiver for activities of daily living. Intensive, multi-disciplinary intervention resulted in minimal improvement in communicative skills and sensory seeking over six months. Subsequently, a tailor-made picture-assisted communication training with the mother as the communication facilitator was adopted. This approach was abandoned due to the patient’s poor response and mother’s low acceptance of picture-based interaction. A preference for printed material was observed in the patient. Accordingly, further management was focused on employing a computer-based interactive platform that the patient was taught to use over the course of a few months as a part of augmentative and alternative communication (AAC) intervention program. This resulted in a remarkable improvement in the child’s skills that now allowed for a better intentional communication of his thoughts and needs.

Conclusions: This study highlights the importance of revisiting conventional rehabilitation strategies for communicative deficits and tailoring them according to the patient’s needs and preferences. It also emphasises that besides excellent observation skills, clinicians must be willing to consider technology based approaches in patients responding poorly to traditional approaches in order to develop effective interventional programmes.

• Implication for Rehabilitation

• The current study highlights the importance of exploring the application of technology based intervention for building communication skills in the early stages of rehabilitation for persons with communicative deficit.

• It also emphasises the need for excellent observation skills among clinicians so that the peculiar interests of children with ASD may be applied in designing training programmes to overcome communication barriers.

• Additionally, clinicians should familiarise themselves with the latest assistive technology-based rehabilitation approaches and be willing to explore newer approaches if traditional ones fail to yield satisfactory outcomes.

• Use of technology-based interventions to reduce dependence among persons with disability would be beneficial, both socially and economically, in developing countries with limited resources.

     

Investigation into defect chemistry and relaxation processes in niobium doped and undoped SrBi4Ti4O15 using impedance spectroscopy

The aurivillius family of compounds SrBi₄Ti₄O₁₅ (SBTi) and SrBi₄Ti_3.8Nb_0.2O₁₅ has been prepared using solid state reaction techniques. The niobium doping enhances the value of the dielectric constant, but decreases the phase transition temperature and grain size of SBTi. Grain conductivity evaluated from the impedance data reveals that Nb doping increases the resistance of grains which indicates the decrease in oxygen vacancies. The negative temperature coefficient of resistance shown by the grain boundary conductivity is explained using the Heywang–Jonker model. The variation of ac conductivity with frequency is found to obey Jonscher’s universal power law. The frequency exponent (n), pre-exponential factor (A), and bulk dc conductivity (σ_dc) are determined from the fitting curves of Jonscher’s universal power law. From the frequency exponent (n) versus temperature curve, we conclude that the conduction mechanism of SBTi changes from large-polaron tunneling (300–475 °C) to small-polaron tunneling (475–550 °C), and in that of the niobium doped it is small-polaron tunneling (300–375 °C) to correlated band hopping (375–550 °C). Activation energies have been calculated from different functions such as loss tangent, relaxation time, grain and grain boundary conductivities, and ac and dc conductivity. The activation energies reveal that conductivity in the sample has contributions from migrations of oxygen vacancies, bismuth ion vacancies, electrons ionized from strontium vacancies, strontium ion vacancies and valence fluctuations of Ti⁴⁺/Ti³⁺ ions.

From the analysis of impedance, ac conductivity we conclude that the donor ion Nb⁵⁺ doping in SrBi₄Ti₄O₁₅, reduces the oxygen vacancy and improves the dielectric and ferroelectric properties.     

Introducing chemical functionality in Fmoc-peptide gels for cell culture

Aromatic short peptide derivatives, i.e. peptides modified with aromatic groups such as 9-fluorenylmethoxycarbonyl (Fmoc), can self-assemble into self-supporting hydrogels. These hydrogels have some similarities to extracellular matrices due to their high hydration, relative stiffness and nanofibrous architecture. We previously demonstrated that Fmoc-diphenylalanine (Fmoc-F₂) provides a suitable matrix for two-dimensional (2D) or three-dimensional (3D) culture of primary bovine chondrocytes. In this paper we investigate whether the introduction of chemical functionality, such as NH₂, COOH or OH, enhances compatibility with different cell types. A series of hydrogel compositions consisting of combinations of Fmoc-F₂ and n-protected Fmoc amino acids, lysine (K, with side chain R = (CH₂)₄NH₂), glutamic acid (D, with side chain R = CH₂COOH), and serine (S, with side chain R = CH₂OH) were studied. All compositions produced fibrous scaffolds with fibre diameters in the range of 32–65 nm as assessed by cryo-scanning electron microscopy and atomic force microscopy. Fourier transform infrared spectroscopy analysis suggested that peptide segments adopt a predominantly antiparallel β-sheet conformation. Oscillatory rheology results show that all four hydrogels have mechanical profiles of soft viscoelastic materials with elastic moduli dependent on the chemical composition, ranging from 502 Pa (Fmoc-F₂/D) to 21.2 KPa (Fmoc-F₂). All gels supported the viability of bovine chondrocytes as assessed by a live–dead staining assay. Fmoc-F₂/S and Fmoc-F₂/D hydrogels in addition supported viability for human dermal fibroblasts (HDF) while Fmoc-F₂/S hydrogel was the only gel type that supported viability for all three cell types tested. Fmoc-F₂/S was therefore investigated further by studying cell proliferation, cytoskeletal organization and histological analysis in 2D culture. In addition, the Fmoc-F₂/S gel was shown to support retention of cell morphology in 3D culture of bovine chondrocytes. These results demonstrate that introduction of chemical functionality into Fmoc-peptide scaffolds may provide gels with tunable chemical and mechanical properties for in vitro cell culture.