Elucidation of the role of α-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice.

OBJECTIVE: Although methotrexate (MTX) is used to treat several malignancies and chronic inflammatory diseases, its clinical use is constrained because of its negative side effects, the most prevalent of which are hepatotoxicity and nephrotoxicity. So, this study aims to determine whether α-lipoic acid (ALA) and vitamin C can protect mice against the liver damage that methotrexate causes. MATERIALS AND METHODS: A total of 49 male mice were divided into seven groups at random. Group I received sodium bicarbonate, while groups II to VII received an intraperitoneal injection of MTX (20 mg/kg) on the tenth day, following ten days of pretreatment with ALA (60 mg/Kg), ALA (120 mg/Kg), vitamin C (100 mg/Kg), vitamin C (200 mg/Kg), ALA (60 mg/Kg), and vitamin C (100 mg/kg). RESULTS: When compared to mice in group I, mice in group II (the control group) had significantly higher levels of the enzymes malondialdehyde (MDA), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significantly lower (p <0.05) levels of the enzymes superoxide dismutase (SOD) and glutathione (GSH). As compared to the control group, pretreatment groups with ALA and vitamin C showed a dose-dependent substantial rise (p <0.05) in GSH and SOD levels, a dose-dependent notable decrease (p <0.05) in MDA, ALT, ALP, and LDH levels, and better liver histological architecture. In order to increase the antioxidant capacity, pretreatment with ALA and vitamin C may be able to prevent MTX-induced hepatotoxicity. CONCLUSIONS: These results imply that ALA and vitamin C are useful in the treatment of MTX-induced liver damage.

Primary extraskeletal Ewing's sarcoma presenting as an axillary mass: A case report and review of the literature.

Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor predominantly observed in adolescents and young adults, and is characterized by aggressive behavior. So far, only two cases of primary axillary soft tissue EES have been reported in the literature. One of them was a 29-year-old female patient who presented with a lump in her left axilla. Upon examination, an irregular, painless mass, measuring 5 cm × 5 cm × 3 cm, was noted in the left axilla. A histopathological examination of the mass revealed small, round, blue cells with scant cytoplasm, round nuclei, numerous mitosis, and necrosis. An immunohistochemistry (IHC) examination was positive for CD99 and negative for ER, PR, Her2neu, CK7, CK5/6, CD56, CD45, CK-pan, CKHMW, P63, desmin, S100, TdT, vimentin, myogenin, synaptophysin, and chromogranin A. The patient was diagnosed with primary axillary soft tissue EES and was started on neoadjuvant chemotherapy. Twelve months later, she is clinically free from the disease.

On solving the chlorine transport model via Laplace transform.

This paper analyzes the two-dimensional chlorine-transport model in pipes. The studied model is in the form of a second-order partial differential equation with a set of boundary conditions. Obtaining exact solution for the current model is a challenge due to the nature of the involved boundary conditions, especially, when applying the Laplace transform. However, such difficulties are solved via implementing the method of residues. The exact solution is obtained in terms of the Bessel functions. The expression for a dimensionless cup-mixing average concentration is also derived analytically. The proposed approach is validated via numerical examples for comparing the results with those in the literature. The present analysis/approach is effective/straightforward and can be further applied on other similar models under different boundary conditions.

Granular cell tumour of the breast in a young female: A case report and literature review.

A granular cell tumour (GCT) of the breast is a relatively uncommon lesion. Often, it mimics carcinoma on clinical and radiological examinations. The striking feature of GCT is the presence of abundant granular eosinophilic cytoplasm, which can easily lead to a misdiagnosis of apocrine carcinoma or a metastatic lesion and may result in unnecessary surgery. To obtain a correct diagnosis, immunohistochemistry with S100 is required. We present a case of a GCT of the breast in a 19-year-old female who presented with a firm mass in the upper inner quadrant of the left breast, which was reported on a mammogram as the Breast Imaging Reporting and Data System (BIRADS) Category 4C. This report is of interest due to the young age of the patient and the rarity of the lesion. To our knowledge, this is the second reported case in all of Saudi Arabia and the first from the Madinah region.

A homozygous potentially pathogenic variant in the PAXBP1 gene in a large family with global developmental delay and myopathic hypotonia.

PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22.11 and identified a homozygous missense variant (c.1612C>T) in the PAXBP1 gene, respectively. This variant is predicted to change the highly conserved strongly basic arginine at position 538 in the PAX7 binding domain of PAXBP1 to a neutral cysteine (p.Arg538Cys) residue. Arg538 is highly conserved and the variant is predicted to be deleterious by variety of in silico tools. Furthermore, protein modeling studies showed that in the mutant protein (Cys538), the shorter cysteine is incapable of forming hydrogen bond with the side chain of nearby Asp517 due to its reduced size and lower polarizability. As a consequence, a slight local perturbation of the loop conformation in the PAX7 binding domain of the PAXBP1 protein was observed. Our findings suggest that the pathogenic variant in PAX binding protein underlies distinct syndrome of global developmental delay and myopathic hypotonia. This clinical report should prompt a search for mutations in PAXBP1 in patients presenting with developmental delay and hypotonia. Moreover, these results imply that establishment of PAXBP1 targets and its spatiotemporal interaction will help in understanding of development of cerebellar and will provide basis for developing therapeutic approaches.