Fluorescence based methodology with greenness consideration for concurrent estimation of anti-allergic medication; application to dosage form.

A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.

Role of motor proteins in human cancers.

Motor proteins include several protein families (Kinesin, Dynein and Myosin) responsible for intracellular transport, intercellular communication, among other functions. In cancer cells, motor proteins along with microtubules (MT) and other tubulin and actin structures, are crucial for cell proliferation and invasion. The cBioPortal platform for Cancer Genomics database was queried for solid cancers in a combined cohort of 9204 patients with complete cancer genomics data. To assess the importance of motor proteins in cancer, copy number alterations (CNAs) and survival rates were analyzed in the combined dataset. Kinesin, Dynein, and Myosin families showed CNAs in 47%, 49%, and 57 % of patients, respectively, in at least one of their members. Survival analysis showed that CNAs in Kinesin and Dynein, families' genes in the same patients were significantly correlated to decreased overall survival. These results added more evidence to previous literature highlighting the importance of motor proteins as a target in cancer therapy. Kinesin inhibitors could act by several mechanisms such as inhibiting spindle assembly or centrosome separation during mitosis, leading to cell cycle arrest and eventually apoptosis. Dynein inhibitors modulate Dynein's activity and MT binding, inhibiting cell proliferation and invasion. Myosin inhibitors act by stabilizing MT, inducing cell cycle arrest and inhibiting invasiveness. Increasing the specificity of motor proteins targeting drugs could improve cancer therapy and patient survival.

Mutational pattern of PIK3CA exon 20 in circulating DNA in breast cancer.

Breast cancer (BC) is one of the most common cancers with diverse mutations, etiology and causes. Mutational signature of the driver genes could allow for better understanding disease etiology and progression. This study aims to assess PIK3CA Exon 20 somatic mutational signature in relation to potential underlying etiology. Circulating DNA of 71 Egyptian BC patients was isolated, amplified for PIK3CA Exon 20, and sequenced. Mutational signature was determined according to COSMIC v2 signature. Public BC dataset was analysed to assess PIK3CA mutations effect on the transcriptomic profile. Somatic mutations of PIK3CA exon 20 were found in 66.2% of the study cohort. Nucleotide substitution patterns were similar to general nucleotide substitution patterns in BC. Signature 3 and 9 were the most common signatures in the studied BC patients. Signature of Aristolochic acid exposure was found in some cases. The most common nucleotide substitution was T > A transversion, but substitutions T > G and T > C were correlated to each other and to the total mutation number. PIK3CA mutations were found to disrupt several pathways including RAC1, PDGF, Wnt, and integrin signalling. PIK3CA exon 20 mutational signatures in Egyptian BC patients could suggest a disease etiology involving homologous recombination deficiency (HRD) and polymerase eta (Pol η). Nucleotide substitution patterns could indicate the role of exposure to oxidative stress and some carcinogens such as 4-aminobiphenyl and Aristolochic acid.

Effect of whole-body vibration on abdominal thickness and sitting ability in children with spastic diplegia.

OBJECTIVE: Reduced muscle and bone mass, improper muscle function, and varying degrees of mobility dysfunctions are the main complications of cerebral palsy (CP). Many children with CP also present with poor abdominal muscle activation. Whole-body vibration (WBV) is a unique approach for enhancing strength and motor abilities in several clinical conditions. This study aimed to determine the influence of a 12-week WBV intervention on the thickness of the abdominal muscles and the sitting ability of children with diplegia. METHODS: A total of 30 children with spastic diplegic CP (aged 4-6 years) were randomly divided into two groups (control and experimental). The control group received a selected physical therapy program for 1 h, and the study group received WBV training for 10 min in addition to the same selected program for the control group for 3 times/week over a period of 12 weeks. Thereafter, abdominal muscle thickness and sitting ability were measured using ultrasonography and the Gross Motor Function Measure-88 (GMFM-88, sitting domain). RESULTS: Post treatment values revealed significant improvement in the measured variables in favour of the experimental group (p < 0.05), as there was improvement in the thickness of the four abdominal muscles compared to the control group (external oblique: F = 38.783; internal oblique: F = 99.547; transverse abdominis: F = 111.557, and rectus abdominis: F = 129.940, p < 0.05). Additionally, the study group showed a significantly greater improvement in GMFM-88 values compared to the control group (F = 129.940, p < 0.05). CONCLUSION: WBV can be a viable strategy for improving sitting ability and abdominal muscle thickness among children with spastic diplegia.

Epidemiological Characteristics and Etiology of Budd-Chiari Syndrome in Upper Egypt.

BACKGROUND AND OBJECTIVES: Budd-Chiari syndrome (BCS) is a rare disorder caused by obstruction to hepatic venous outflow. It affects all races, usually during the third or fourth decade of life. Higher prevalence had being evident in developing countries. The aim of the present study was to clarify sociodemographic features, clinical, radiological presentations, and etiology of BCS among Upper Egyptian patients. PATIENTS AND METHODS: This retrospective cohort study enrolled 50 Upper Egyptian Patients with confirmed primary BCS. Liver, coagulation, and thrombophilia workup profiles were performed as anticardiolipin antibodies, lupus anticoagulant, protein C, protein S, and antithrombin III assays. Factor V Leiden and JAK2 mutations were assessed. Full radiological assessment was done. RESULTS: Fifty patients were included. There were 28 males (56%) and 22 females (44%) with mean age (32.5 ± 11.1 years). The etiological factor was not identified in 22% of cases (n=11). Isolated factor C deficiency was found in 26% (n=13) with male predominance 39.3% and protein S deficiency in 10% (n=5). Factor V Leiden mutation was the etiology in 5 patients (10%). Membranous web and antiphospholipid syndrome each were the etiology in 8% (n=4). Behςet's disease was diagnosed in 4% (n=2). Cases of liver cirrhosis(LC) were 41/50(82%)they were :33/50(66%) LC child class C, 8 /50(16%)  LC child class B, and 0/50 (0%) LC child class A. Abdominal pain was the most common symptom (96%), and ascites was the most common sign (82%). Obstruction of hepatic veins was present in 80%. CONCLUSION: BCS in Upper Egyptian patients was mainly occurred in males in the third and fourth decade of life, mostly with liver cirrhosis. The most common etiology is isolated protein C deficiency followed by Factor V Leiden mutation and isolated protein S deficiency. Hepatic veins obstruction was the most common pattern of vascular involvement.

Plasma endoglin in Type2 diabetic patients with nephropathy.

BACKGROUND: Diabetic nephropathy may be a common complication of diabetes mellitus. Endoglin is glycoprotein located on cell surfaces of endothelial cells and is part of the transforming growth factor beta (TGF- ß) receptor. Endoglin expression is enhanced in endothelial cells during injury and inflammation. The aim of this study was to estimate the plasma level of soluble endoglin (sEng) in type 2 diabetic patients (with and without nephropathy). Also to explore its availability as marker for disease progression. METHODS: In this study, sixty eight patients with type 2 diabetes mellitus (T2DM) were included; the patients were sub-grouped to normoalbuminuria without nephropathy and moderately increased albuminuria (microalbuminuria) with nephropathy groups with 13 individuals as control group. Plasma soluble endoglin level was determined using ELISA technique. Fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), lipid profile, and creatinine were determined using colorimetric assay, whereas glomerular filtration rate (GFR) was calculated. RESULTS: The plasma level of sEng of both normoalbuminuria group 1 and microalbuminuria group 2 were significantly higher when compared to control group. While, the plasma level of sEng in microalbuminuria group 2 was nonsignificant lower when compared to normoalbuminuria group 1. Also, there was a significant positive association between plasma level of sEng and HbA1c, HDL-C and urinary albumin concentration in normoalbuminuria group. CONCLUSION: Plasma level of soluble Endoglin is markedly increase prior to alteration in endothelial function, and increases to lesser extent with the developing of diabetic nephropathy which indicated disease progression and development of vascular abnormalities.

Does the Type of Toeing Affect Balance in Children With Diplegic Cerebral Palsy? An Observational Cross-sectional Study.

OBJECTIVE: The purpose of the study was to find out effect of toeing on balance in children with diplegic cerebral palsy. METHODS: An observational study was conducted. Thirty children with spastic diplegic cerebral palsy, aged 5 to 8 years, participated in this study. They were classified into 2 groups: group A was children with out-toeing, and group B was children with in-toeing. Foot progression angle was measured by using dynamic footprint, and balance was evaluated using Biodex Balance System equipment. The outcome of interest was postural control (overall stability, anteroposterior stability, and mediolateral stability). RESULTS: Statistical analysis revealed a significant difference for the tested variables of interest between the 2 tested groups. Multiple pairwise comparison tests revealed that there was significantly better overall stability, anteroposterior stability, and mediolateral stability (P < .05) in group A. CONCLUSION: It can be concluded that children with out-toeing have higher balance and stability than children with in-toeing.

Lansoprazole halts contrast induced nephropathy through activation of Nrf2 pathway in rats.

Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury characterized by significant mortality and morbidity. To date, there is no successful protective regimen for CIN especially in poor kidney function patients. Lansoprazole has been shown to exert antioxidant action through induction of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. The aim of the present study is to investigate the potential of lansoprazole to activate Nrf2 pathway in the kidney and consequently to protect against oxidative stress induced by iodinated contrast media. Lansoprazole, at a dose of 100 mg/kg, showed a significant induction of Nrf2 mRNA after 3 h. Administration of contrast media induced significant increase in serum creatinine and blood urea nitrogen, histological deterioration, and reduction in total antioxidant capacity. Moreover, it instigated the defensive Nrf2 gene expression and immunoreactivity. In addition, there were overexpression of HO-1, caspase 3, p53 and IL6 genes and downregulation of Bcl2 gene. Pre-treatment with lansoprazole (100 mg/kg) ameliorated the nephrotoxicity parameters and oxidative stress, improved histological lesions, and hijacked apoptotic and inflammatory markers that were provoked by contrast media. In conclusion, lansoprazole attenuates experimental CIN which might be due to activation of Nrf2 antioxidant defence pathway. These findings highlight the potential benefit of incorporating lansoprazole in the protective regimen against CIN especially for susceptible patients.