Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)-Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells.

A novel ruthenium(III)-pyrimidine Schiff base was synthesized and characterized using different analytical and spectroscopic techniques. Molecular geometries of the ligand and ruthenium complex were investigated using the DFT-B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Various biological and molecular docking studies of the complex are reported to explore its potential application as a therapeutic drug. Cytotoxicity of the complex was screened against cancer colorectal (HCT116), breast (MCF-7 and T47D), and hepatocellular (HepG2) cell lines as well as a human normal cell line (HSF). The complex effectively inhibited the tested cancer cells with variable degree with higher activity towards HepG2 (IC50 values were 29 µM for HepG2, 38.5 µM for T47D, 39.7 µM for HCT, and 46.7 µM for MCF-7 cells). The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. The complex significantly induced the expression of H2AX and caspase 3 and caspase 7 gene and the protein level of caspase 3, as well as inhibited VEGF-A and mTOR/AKT, SND1, and NF-kB gene expression. The molecular docking studies supported the increased total apoptosis of treated HepG2 cells due to strong interaction of the complex with DNA. Additionally, the possible binding interaction of the complex with caspase 3 could be responsible for the elevated activity of caspase 3-treated cells. The score values for the two receptors were -3.25 and -3.91 kcal/mol.

Purification and Characterization of Ornithine Decarboxylase from Aspergillus terreus; Kinetics of Inhibition by Various Inhibitors.

l-Ornithine decarboxylase (ODC) is the rate-limiting enzyme of de novo polyamine synthesis in humans and fungi. Elevated levels of polyamine by over-induction of ODC activity in response to tumor-promoting factors has been frequently reported. Since ODC from fungi and human have the same molecular properties and regulatory mechanisms, thus, fungal ODC has been used as model enzyme in the preliminary studies. Thus, the aim of this work was to purify ODC from fungi, and assess its kinetics of inhibition towards various compounds. Forty fungal isolates were screened for ODC production, twenty fungal isolates have the higher potency to grow on L-ornithine as sole nitrogen source. Aspergillus terreus was the most potent ODC producer (2.1 µmol/mg/min), followed by Penicillium crustosum and Fusarium fujikuori. These isolates were molecularly identified based on their ITS sequences, which have been deposited in the NCBI database under accession numbers MH156195, MH155304 and MH152411, respectively. ODC was purified and characterized from A. terreus using SDS-PAGE, showing a whole molecule mass of ~110 kDa and a 50 kDa subunit structure revealing its homodimeric identity. The enzyme had a maximum activity at 37 °C, pH 7.4-7.8 and thermal stability for 20 h at 37 °C, and 90 days storage stability at 4 °C. A. terreus ODC had a maximum affinity (Km) for l-ornithine, l-lysine and l-arginine (0.95, 1.34 and 1.4 mM) and catalytic efficiency (kcat/Km) (4.6, 2.83, 2.46 × 10-5 mM-1·s-1). The enzyme activity was strongly inhibited by DFMO (0.02 µg/mL), curcumin (IC50 0.04 µg/mL), propargylglycine (20.9 µg/mL) and hydroxylamine (32.9 µg/mL). These results emphasize the strong inhibitory effect of curcumin on ODC activity and subsequent polyamine synthesis. Further molecular dynamic studies to elucidate the mechanistics of ODC inhibition by curcumin are ongoing.

Accuracy of Arabic versions of three asthma symptoms questionnaires against the clinical diagnosis of asthma.

Validation studies of asthma symptom questionnaires against provocation tests of bronchial hyperresponsiveness have shown comparable performances of written and video taped questionnaires. This study aimed to determine the test characteristics of Arabic versions of two written and one video taped questionnaires when compared to the clinical diagnosis of asthma made by two respiratory physicians. The written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire had higher sensitivities and greater accuracy than the other two questionnaires. Comparisons between corresponding questions and scenes in the ISAAC questionnaires in general revealed no significant differences in performance. The ISAAC written questionnaire had test characteristics consistent with its potential use as a screening instrument for asthma in this population of children.

Demographics and microbiological profile of pneumonia in United Arab Emirates.

BACKGROUND: Pneumonia is a common respiratory disease, which has a mortality rate of approximately 14% worldwide. The management of pneumonia is based on the patient and microbiological profile existing in the community. There is a paucity of data regarding patient demographics and the microbiological profile for pneumonia in the United Arab Emirates (UAE). METHODS: We conducted a retrospective analysis of in-patients with pneumonia in the UAE. Epidemiological, clinical and microbiological data was collected from patients over the age of 16 years admitted to a single university hospital with a diagnosis of pneumonia between the years 1997 and 2002. Patients were categorised as having community acquired (CAP) or hospital acquired pneumonia (HAP). RESULTS: Among the 361 patients, 186 were females and 175 males. The mean age (+/- SEM) of the males was 59 +/- 1.6 years and of the females, 56.9 +/- 1.5 years. The annual hospital admission rate for pneumonia increased from 410 per million population in 1997 to 760 in 2002. The pneumonia was community acquired in 289 (80%) and hospital acquired in 72 (20%). Hospitalisation for CAP showed a significant seasonal variation with peak admission rates in March and April and the nadir in August and September. The overall mortality rate was 13%, and was significantly higher for HAP (24%) than for CAP (10%, p < 0.01). The common microorganisms isolated from sputum culture in CAP were Haemophilus influenzae (18.6%) and Streptococcus pneumoniae (10%). The common pathogen in HAP was Pseudomonas aeruginosa in (50%). 4 out of 17 (23%) H. influenzae isolates were resistant to amoxicillin and 2 of 9 S. pneumoniae isolates (22%) were resistant to penicillin. CONCLUSIONS: The hospitalisation rate for CAP has increased over the years and showed a clear seasonal trend in the UAE. H. influenzae was the most common organism among patients with CAP and P. aeruginosa in HAP. The mortality rate for HAP was significantly higher than for CAP. The drug resistance pattern was similar to reports from centres elsewhere in South East Asia.

An analysis of skin prick test reactions in asthmatics in a hot climate and desert environment.

BACKGROUND: Studies have shown that allergens are very important sensitizing agents in patients with asthma. Respiratory disorders such as asthma and allergic rhinitis are common in the United Arab Emirates, (UAE). OBJECTIVES: The aim of this study was to investigate the relationship between allergen specific IgE antibodies and skin test reactivity in patients with asthma in hot climate and desert Arabian country. DESIGN: A hospital-based prospective study conducted. SETTING: Tawam Teaching Hospital, Al-Ain, UAE. PATIENTS: 327 adult patients recruited with respiratory, dermatologic and ophthalmologic diseases of suspected allergic origin who attended Tawam Teaching Hospital of Faculty of Medicine, Al Ain, UAE, during three years from 1996 to 1998. METHODS: Skin Prick Test (SPT) and radioallegosorbent tests (RAST) were performed on 327 patients for common allergens. The blood sample was taken for measuring specific IgE concentration. RESULTS: There were 327 UAE patients of whom 117 (35.8%) were males and 210 (64.2%) were females. The population sample had a higher prevalence of diagnosed asthma among females (48.1%) than in males (36.7%). Skin prick testing showed that 244 patients (74.6%) had positive results, and 83 patients (25.4%) were found to be skin test negative. 44% had a positive family history of asthma. The twelve most common reactions in the United Arab Emirates were: Mesquite (45.5%), Grass Mix (40.7%). Cottonwood (33.1%), Bermuda Grass (31.3%), Kochi (25.8%), Acacia (25.6%), Alfalfa (22.9%), Chenopodium (19.6%), Date palm (13.8%), Cockroach (14.7%), house dust (11.9) and Dust mite (9.5%). Total IgE level (> 100 kU/l) was strongly associated with history of wheeze (p = 0.019), asthma (p = 0.01) and allergic rhinitis (p < 0.0001), atopy (p < 0.0001) and the presence of specific IgE antibodies to grass pollen (p < 0.0001), mite (p = 0.008) and cockroaches (p = 0.025). CONCLUSION: The present study revealed that hypersensitivity to pollens, house dust, dust mite and cockroach was common. The family history, environment, and airborne allergens are identified to be risk factors for asthma and other allergic diseases in Arabian Gulf Countries.

X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation.

Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterised by lesions of the skin and appendages. Bone marrow failure occurs in 80% of patients. The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1. Pulmonary manifestations have rarely been reported. It is not known whether there is a respiratory disease peculiar to these patients and, if so, whether it is associated with a specific genetic mutation. A 40 year old Egyptian man with pulmonary disease and his symptom free 35 year old brother both presented with mucocutaneous lesions characteristic of DC. In the older brother chest imaging revealed generalised intralobular interstitial thickening and honeycombing. Pulmonary function tests showed a restrictive pattern. Open lung biopsy specimens of lung tissue showed various degrees of fibrosis consistent with usual interstitial pneumonia of chronic idiopathic pulmonary fibrosis. The younger brother was free of pulmonary lesions. Both had a novel missense mutation 5C-->T in exon 1 of the DKC1 gene. It is concluded that pulmonary disease in DC may be underestimated, possibly because most patients die at an early age of bone marrow failure. No relationship between genotype and phenotype could be established in the patients studied. The genetic diagnosis of DC is now available, which may enable it to be diagnosed in patients with restrictive pulmonary disease and minimal cutaneous signs.