Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism     

A clinical study of Wilson’s disease: The experience of a single Egyptian Paediatric Hepatology Unit

Background and study aimsMost paediatric patients with Wilson’s disease (WD) present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD.Patients and methodsThe study was carried out at the Paediatric Hepatology Unit at Cairo University Children’s Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser–Fleischer (K–F) rings.ResultsThe clinical presentation was as follows: hepatic presentation in 33 patients (61%), hepato-neurologic 3 (5.5%), neurologic 5 (9.3%) and presymptomatic 13 (24%). Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K–F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months (1–36). The hepatic symptoms improved with treatment but the neurological symptoms remained stationary.ConclusionsClinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance.     

Effect of Silicon Nitride and Graphene Nanoplatelets on the Properties of Aluminum Metal Matrix Composites

This research work aims at investigating the influence of a fixed content of silicon nitride (Si₃N₄) and varied contents of graphene nanoplatelets (GNPs) on the physical (density, structural, morphological) and mechanical properties (microhardness, nanoindentation) of Al-Si₃N₄-GNPs composites. The composites were fabricated by a microwave-assisted powder metallurgy route. The Si₃N₄ concentration was fixed at (5 wt.%) in Al-Si₃N₄-GNPs composites while the GNPs concentration was varied between (0 wt.%) to (1.5 wt.%) with an increment of (0.5 wt.%). The structural analysis indicates the formation of phase pure materials with high crystallinity. The microstructural analysis confirmed the presence of the Si₃N₄ and GNPs showing enhanced agglomeration with the increasing amount of GNPs. Moreover, the surface roughness of the synthesized composites increases with an increasing amount of GNPs reaching its maximum value (RMS = 65.32 nm) at 1.5 wt.% of GNPs. The Al-Si₃N₄-GNPs composites exhibit improved microhardness and promising load-indentation behavior during nanoindentation when compared to pure aluminum (Al). Moreover, Al-Si₃N₄-GNPs composites demonstrate higher values of compressive yield strength (CYS) and ultimate compressive strength (UCS) when compared to pure Al despite showing a declining trend with an increasing amount of GNPs in the matrix. Finally, a shear mode of fracture is prevalent in Al-Si₃N₄-GNPs composites under compression loading.     

Safety and effi cacy of hepatitis A vaccine in children with chronic liver disease

INTRODUCTION Hepatitis A virus (HAV) infection is common. In general, hepatitis A is a self-limited illness with a recovery time measured in months[1]. Young children are often asymptomatic, whereas adults are more likely to be symptomatic and may present…     

Clinical practice

Four patients with tyrosinemia type 1 (ages 6–32 months) were treated with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexandion (NTBC) at Cairo University Children’s Hospital, Egypt and followed up for 12–27 months. The recommended average dose of NTBC is 1 mg/kg/day. They were started on the following doses: 0.8, 0.58, 0.5, and 0.625 mg/kg/day, respectively. Two months after start of therapy, succinylacetone was undetectable in patients 1, 2, and 4, while in case 3, it was 5.4 μM. Her NTBC dose was increased from 0.5 to 0.65 mg/kg/day, and succinylacetone was undetectable 1 month later. They were kept on NTBC doses ranging from 0.55 to 0.65 mg/kg/day. These doses allowed catch up growth, normalization of synthetic liver functions, steep drop in serum alpha fetoprotein, reduction in phosphate loss in urine, normalization of serum calcium, phosphate, and alkaline phosphatase, and healing of active rickets. Succinylacetone was undetectable in urine on these doses. In conclusion: Doses of NTBC, lower than recommended, may be helpful in treatment of tyrosinemia, on condition that succinylacetone production is suppressed, and AFP is maintained normal or showing a progressive decrease. This cost-effective dose may allow treatment of affected children from economically underprivileged countries, but longer follow up periods are needed.     

Morphological Study of the Lingual Papillae in Mellivora capensis Tongue

Background： The present study was conducted on the three Mellivora tongues, and the tongue was divided into three portions, apex, body and base. The tongue was tapered at the apex, wider in the middle and had elevation at the base, which termed torus linguae. The tongue is triangular in shape, and the length of tongue ranged between 58-60 mm. The dorsum linguae of this wild animal were characterized by presence of median groove. Methods： After killing, the Mellivora capensis were skinned and the heads were dissected to approach the tongue. The tongues were prepared for morphometric and morphological studies. Results： The morphological study revealed five types of lingual papillae （filiform, conical, fungiform, circumvallate and foliate）. The filiform were numerous and scattered on the entire dorsal and lateral surfaces. They were thread like projections, and found in different forms （single, bifurcated, trifurcated and serrated end）. The conical papillae were found among the filiform papillae with rounded ends. The fungiform papillae have dome or mushroom-shapes and distributed at the apex of the tongue. The circumvallate papillae were globular or circular shapes and surrounded by trench and located at posterior of tongue between the end of body and torus linguae. The foliate papillae were found on the posterio-lateral surface of the tongue, ridges-shaped and were separated by grooves. Conclusion： The present study showed five types of dorsal lingual papillae： filiform, conical, fungiform, cicumvallate and foliate.     

A novel protocol for postpartum magnesium sulphate in severe pre-eclampsia: a randomized controlled pilot trial

Objective: Magnesium sulphate is the preferred anticonvulsant used to prevent the development of fits in severe pre-eclampsia; we aim to compare between three different protocols of postpartum magnesium sulphate in the effectiveness of preventing the development of fits in severe pre-eclampsia.

Methods: Double-blind randomized controlled pilot trial, done in Cairo university hospital, Cairo, Egypt during 2013–2014, on 240 women with severe pre-eclampsia. Magnesium sulphate intravenous infusion was given in the postpartum period to all the patients, women were randomly allocated to group I (Single loading dose only), group II (12?h abbreviated protocol) or group III (24?h standard protocol) (n?=?80 in each group).

Results: There were no significant difference between the three groups as regards the incidence of eclampsia, elevated liver enzymes and low platelets syndrome, maternal ICU admission and; however The incidence of flushing was significantly higher in group III than group II and I (24 [30%] versus 12 [15%] versus 4 [5%]; p?<?0.001) respectively.

Conclusion: The pilot study demonstrates that the single-loading dose of postpartum magnesium sulphate is a promising alternative to the standard and the abbreviated protocol in preventing eclampsia; however, a large clinical trial is necessary to prove this.