Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient

Introduction/Objective Valproic acid is a branched short chain fatty acid derivative that is used primarily to treat epilepsy as well as mood disorders, certain types of headaches, and neuropathic pain. It is commonly prescribed in the pediatric population and has shown to be effective for refractory epilepsy with adequate seizure control. Serious side effects may be prominent if the medication is not kept at the therapeutic range. A wide variety of known hematologic problems can be encountered including but not limited to anemia, thrombocytopenia, and leukopenia. Methods/Case Report We present a case of a pediatric patient with a past medical history significant for history of seizure disorder and who presented to Jackson Memorial Hospital for intermittent fevers and multiple unexplained bruises for 3 weeks as well as fatigue and weakness.The patient was recently started on valproic acid. Complete blood count (CBC) was obtained and showed a platelet count of 23 x10(3)/mcL with WBC of 3.5 x10(3)/mcL and hemoglobin of 9.7 g/dL.Serum valproate concentration was critically high (154 mg/L). Trephine biopsy showed a normocellular marrow (60%) showing maturing trilineage hematopoiesis and scattered atypical megakaryopoiesis characterized by small forms that are seen in relatively loose interstitial clusters (Figure 1). The marrow aspirate smears were characterized by cellular spicules with dysmegakaryopoiesis including numerous small hypolobated forms with frequent forms showing separated nuclei (Figure 2, 3, and 4). Blasts did not appear increased, comprising overall 1% of marrow cellularity. Karyotype studies revealed a normal female karyotype, 46, XX. FISH studies using probes commonly detected in MDS were negative. Next generation sequencing was negative for AML specific mutations including GATA1 and GATA2 mutations. Results (if a Case Study enter NA) N/A Conclusion This case report highlights the significant hematologic adverse effects of valproic acid, specifically pancytopenia with dysmegakaryopoiesis, raising the clinical suspicion of potential myelodysplastic syndrome. Critically high level of valproic acid (154 mg/L) and normalization of CBC after the stoppage of the medication strongly suggests that valproic acid can cause severe bone marrow suppression and specific morphologic atypia in the megakaryocytic lineage thus introducing a potential diagnostic pitfall. Because the CBC returned to normal, bone marrow biopsy was not repeated.

Neuroblastoma GD2 Expression and Computational Analysis of Aptamer-Based Bioaffinity Targeting

Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal residual disease (MRD) that causes relapse. Whilst there exists a myriad of advanced treatment options for NB, it is still characterized by a high relapse rate, resulting in a reduced chance of survival. Disialoganglioside (GD2) is a lipo-ganglioside containing a fatty acid derivative of sphingosine that is coupled to a monosaccharide and a sialic acid. Amongst pediatric solid tumors, NB tumor cells are known to express GD2; hence, it represents a unique antigen for subclinical NB MRD detection and analysis with implications in determining a response for treatment. This article discusses NB MRD expression and analytical assays for GD2 detection and quantification as well as computational approaches for GD2 characterization based on high-throughput image processing and genomic data analysis.

Effectiveness of isolated compound from Aloe barbadensis Miller and its formulated ointment against bacteria and fungi

Ethnomedicinally, the family Liliaceae is prominent in controlling skin, wound and fungal infections. A carboxylic fatty acid derivative has been isolated from Aloe vera leaves and its structure was elucidated on the basis of NMR and FT-IR analysis. The compound was formulated as ointment with the aid of polymer based delivery agent. The ointment and the uncontaminated fatty acid have been scrutinized aimed at their anti-infectious potential. Individually, the pure compound and the formulated ointment exhibited growth inhibitory activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans and Talaromyces flavus. Minimum inhibitory concentration (MIC) values were found to be appreciably low, ranging between 0.30 and 2.50 mg/ml. The formulated ointment displayed highly significant inhibitory activities against all six pathogens compared to the unformulated compound. The MIC values of the ointment ranged between 0.08 and 1.25 mg/g. The in vitro antibiotic activity studies discovered that, both the pure compound and the formulated ointment showed potency against the selected multi-resistant microorganisms tested in the current work. These findings suggest that the isolated carboxylic acid derivative may be beneficial in the discovery of antibiotics highly potent against drug-resistant pathogens. Furthermore, it may add to the improvement of preservatives in the food industry. Lastly, it could be considered as new source of natural antibiotics in the pharmaceutical industry.

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6’-O-octadeca-8″,11″-dienoyl)-sitosterol-3-O-β-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.

Mesomorphic, Optical and DFT Aspects of Near to Room-Temperature Calamitic Liquid Crystal

A new liquid crystalline, optical material-based Schiff base core with a near to room-temperature mesophase, (4-methoxybenzylideneamino)phenyl oleate (I), was prepared from a natural fatty acid derivative, and its physical and chemical properties investigated by experimental and theoretical approaches. The molecular structure was confirmed by elemental analysis, FT-IR (Fourier-Transform-Infrared Spectroscopy) and NMR (nuclear magnetic resonance) spectroscopy. Optical and mesomorphic activities were characterized by differential scanning calorimetry (DSC) and polarized optical microscopy (POM). The results show that compound (I) exhibits an enantiotropic monomorphic phase comprising a smectic A phase within the near to room-temperature range. Ordinary and extraordinary refractive indices as well as birefringence with changeable temperatures were analyzed. Microscopic and macroscopic order parameters were also calculated. Theoretical density functional theory (DFT) calculations were carried out to estimate the geometrical molecular structures of the prepared compounds, and the DFT results were used to illustrate the mesomorphic results and optical characteristics in terms of their predicted data. Three geometrical isomers of the prepared compound were investigated to predict the most stable isomer. Many parameters were affected by the geometrical isomerism such as aspect ratio, planarity, and dipole moment. Thermal parameters of the theoretical calculations revealed that the highest co-planar aromatic core is the most stable conformer.