Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA)–containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings. Patients and Methods: The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron) with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications) and nausea control (no nausea), which were assessed in the acute (0 to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases. Results: The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients). Conclusion: An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar with olanzapine-containing regimens, because NK1RA agents are not affordable and not easily available.

Background: ABCB1 (MDR1) is a transporter glycoprotein that has a major role in drug effluxes and resistance. Single nucleotide polymorphisms (SNPs) in ABCB1gene may affect protein expression, disease susceptibility and drug response, side effects and pharmacokinetics. The functional impact of most non-synonymous (ns) SNPs is still unclear. This study adopted a Structural bioinformatics approach to predict the effects of nsSNPs on ABCB1 structure and function. Methodology: The effects of coding nsSNPs were predicted by SIFT, PolyPhen-2, PANTHER, SNAP, PROVEAN, PhD-SNP and SNPs & GO. Prediction of protein stability changes was analyzed by I-Mutant. The conservation of amino acid positions in a protein was predicted by Consurf. NetSurfP was used to predict the surface accessibility of amino acid residue in protein structure. The impact of substitutions in protein was analyzed using Hope. Chimera was used to visualize changes in the protein 3D structure due to deleterious nsSNPs. Results: The nsSNPs of ABCB1 gene were retrieved from dbSNP database. nsSNPs were analyzed using SIFT and PolyPhen-2. To increase the accuracy of predictions, results of SIFT and PolyPhen-2 were joined and nsSNPs with PolyPhen score> 0.90 and SIFT< 0.05 were selected. Accordingly, three nsSNPs were classified as deleterious/damaging (rs28381902 (E566K), rs1128501 (G185V) and rs9282565 (A80E)). PANTHER, SNPs & GO, PhD-SNP, SNAP and PROVEAN confirmed the damaging effects of the first two nsSNPs, while the damaging effect of the third one was predicted only by PhD-SNP and SNAP. These three nsSNPs were predicted by I-Mutant as significantly decreasing the stability of the protein. ConSurf revealed that the three deleterious nsSNPs were located in intermediately/highly conserved regions. Conclusion: Structural bioinformatics approach proved capable of identifying the most damaging nsSNPs. This study predicted three nsSNPs in the ABCB1 gene as the most damaging. These nsSNPs, to the best of our knowledge, have not yet been investigated and therefore may be considered as candidates for association with diseases and drug response.

Background: Calonysterone (CAL) is a natural derivative of 20-hydroxyecdysone (20E) with enhanced bioactivity on skeletal muscle cells in vitro, but its in vivo physiological actions remain less well characterized. This study aimed to compare the effects of 20E and CAL on metabolic, muscular, and endocrine parameters in normal and obese male rats, with a particular focus on androgen balance. Methods: Male rats were treated with 20E or CAL under normal (ND) or high-fat, high-sugar dietary (HFHSD) conditions for 12 weeks. Body weight, food intake, skeletal and androgen-sensitive muscle mass, and testicular weight were measured. Testicular expression of androgen receptor (Ar) and aromatase (Cyp19a1) mRNA was assessed by RT-PCR. ELISA was used to determine the plasma corticosterone, testosterone and ERβ level in testes. Results: 20E and CAL prevented HFHSD-induced weight gain and skeletal muscle atrophy. CAL uniquely preserved testicular and levator ani muscle mass in obese rats. CAL increased the expression of Cyp19a1 and ERβ in testicles. Decreased Ar mRNA expression was regulated in 20E- and CAL-treated obese animals. While 20E treatment significantly reduced plasma testosterone levels in the normal diet group compared to controls, both 20E and CAL interventions elicited significant reductions in the obese group relative to both the ND and HFHSD groups. HFHSD-induced increase in plasma corticosterone levels was normalized by 20E or CAL treatment. Conclusions: 20E and CAL exhibit beneficial metabolic and anabolic effects by preventing HFHSD-induced obesity and consequential muscle atrophy. CAL counteracts obesity-induced testicular atrophy in terms of tissue mass. Based on our results, we hypothesized that CAL enhances testicular aromatase levels, which may lead to increased compensatory androgen receptor mRNA expression and increased ERβ levels. These complex, not yet fully understood results underscore the need for caution in the use of phytoecdysteroids as dietary supplements.