INVESTIGATING THE MASS SPECTROMETRIC BEHAVIOR OF NOVEL ANTINEOPLASTIC CURCUMIN ANALOGUES

Curcumin analogues are novel antineoplastic agents designed by structural modifications of the natural product curcumin to enhance its therapeutic effects. Various curcumin analogues displayed a significant cytotoxic effect towards different cancer cell lines including leukemia, melanoma, and colon cancer. In order to evaluate the safety, efficiency and metabolism of the new anticancer candidates, sensitive and high throughput analytical methods are needed. Thirteen curcumin analogues with the backbone structure of 3,5-bis(benzylidene)-4-piperidone were tested. The ionization behavior of curcumin analogues was investigated to reveal the possible mechanisms for the unusual formation of the positively charged [M-H]+ ions during single stage positive ion mode MALDI-MS analysis. Different ionization techniques (i.e., ESI, APCI, APPI, and MALDI) were used to evaluate this phenomenon. The results showed that curcumin analogues ionize into [M-H]+ along with the expected [M+H]+ species during MALDI and dopant free APPI-MS. In contrast, ESI, APCI and the dopant mediated APPI showed only the expected [M+H]+ peak. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. Three proposed mechanisms for the formation of [M-H]+ were evaluated, two of them are probably involved in the [M-H]+ formation: (i) hydrogen transfer from the analyte radical cation and (ii) hydride abstraction. In addition to the ionization behavior, the collision induced dissociation-tandem mass spectrometric (CID-MS/MS) fragmentation behavior of curcumin analogues was evaluated showing similar dissociation pathways that centered on the piperidone ring of the 3,5-bis(benzylidene)-4-piperidone moiety. The presence of different substitutes on that moiety resulted in specific product ions for each curcumin analogue. The fragmentation patterns were established to confirm the chemical structure of the tested compounds and identify the diagnostic product ions of each compound. Twelve common product ions were identified resulting from the breakage of various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions that are stabilized via resonance. Common product ions were identified allowing for the establishment of a general MS/MS behavior for any curcumin analogue that belongs to the 3,5-bis(benzylidene)-4-piperidone structural family. The fragmentation routes and the genesis of the product ions were confirmed via MS3 and neutral loss analysis. In summary, the ionization of curcumin analogues provided insights into the formation of unique [M-H]+ ions which were linked to photo ionization of such compounds without the need for additives, such as matrix, dopant or solvent. As such, curcumin analogues should be evaluated as MALDI matrices in the future. The CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of the tested compounds. It will be applied, in the future to determine metabolic by-products of the tested compounds as well as to develop targeted liquid chromatography (LC)-MS/MS methods

Mastitogenic Bacteria Isolated from Clinical Mastitis Cases Associated with Teat Lesions and their Antimicrobial Sensitivity

Mastitis is the most common and most expensive disease that impacts dairy farms in Egypt. In this study, we investigated bacterial mastitis cases that did not respond to antimicrobial treatment from buffaloes and cows. Milk samples (11) were collected from diseased animals (5 buffaloes and 6 cows). The samples were tested microbiologically to isolate and identify the causative bacteria and antimicrobial susceptibility. The antimicrobial sensitivity of the isolated bacteria was tested by using minimum inhibitory concentration technique according to the clinical national laboratory standards.  The total number of bacterial isolates from the cases was 15 isolates. Staphylococcus aureus (S. aureus) was isolated alone in two cases (13.33% of the isolates), and S. aureus isolated in combination with Arcanobacterium pyogenes (A. pyogenes) in one case (6.67%), and S. aureus isolated in combination with both A. pyogenes and Streptococcus agalactiae (S. agalactiae) in two cases (13.33%), and Coagulase negative staphylococci (CNS) isolated alone in one case (6.67%), and CNS isolated in combination with Klebsiella pneumoniae in one case (6.67%), and A. pyogenes isolated alone in two cases (13.33%). In two cases were not able to isolate any bacterial pathogen. In terms of susceptibility to antibiotics, the isolated strains were sensitive to clindamycin with MICs ranging from 0.125 to <0.03125 µM. The same isolates exhibited medium sensitivity to gentamicin and ciprofloxacin with MICs ranging from 0.5 to 8 µM. Most S. aureus isolates were resistant to oxytetracycline with a MIC of 128 µM. Most of the isolated bacteria were resistant to polymyxin B with a MIC > 128 µM. With the exception of the A. pyogenes isolates, all the isolated bacteria were sensitive to enrofloxacin with a MIC <1 µM.       &nbsp

New chemistry with gold-nitrogen complexes: synthesis and characterization of tetra-, tri-, and dinuclear gold(I) amidinate complexes. Oxidative-addition to the dinuclear gold(I) amidinate

Nitrogen ligands have been little studied with gold(I) and almost no chemistry has been described using anionic bridging nitrogen ligands. This dissertation concerns the impact of the bridging ligands amidinate, ArNHC(H)NAr, on the chemistry of gold(I) and, in particular, the effect of substituents on the molecular arrangement. The electronic vs. steric effect of the substituents on the molecular arrangement of gold(I) amidinates complexes is studied in detail. Tetra-, tri-, and dinuclear gold(I) amidinate complexes are synthesized and characterized using X-ray diffraction. Spectroscopic and electrochemical studies of the amidinate complexes are described. Catalytic studies suggest that gold amidinates and related gold nitrogen complexes are the best catalyst precursors for CO oxidation on TiO2 surface reported to date (87% conversion). The dinuclear gold(I) amidinate complex with a Auâ ¦Au distance of 2.711(3) Ã is rare. To our knowledge, there is only one other example of a symmetrical dinuclear gold(I) nitrogen complex. Oxidative-addition reactions to the dinuclear gold(I) complex, [Au2(2,6-Me2-form)2] are studied in detail and result in the formation of gold(II) complexes. The gold(II) amidinate complexes are the first formed with nitrogen ligands. The complexes are stable at room temperature. Mixed ligand tetranuclear gold(I) clusters and tetranuclear mixed Au-Ag metal clusters of pyrazolate and amidinate ligands are synthesized and characterized using Xray diffraction

Occupational Stress, Job Satisfaction and Cervical Screening Intention of Maternity Oncology Nurses

Background: Cervical Cancer could be a preventable disease, and a key aspect of its interference is that the detection of the premalignant form by cervical screening. Nursing could be a skilled job characterized by high stress. Stress could be associated with less practice of health promoting behaviors; however, no study has investigated the relationship between job stress and health screeningbehaviors among nurses in Egypt. Aim: describe the rate of Pap smears in hospital nurses and assess the effects of job stress on receiving cervical cancer screening. Subject and Methods: Purposive sampling included 30 nurses who worked in gynecological inpatient and outpatient department in all general hospitals in Beni-Suef city. Data collection was carried out by self-administered structured questionnaire, Job stressors & Job Satisfaction Scales for Nurses. Results: 86.7% of staff nurses working in maternity oncology units never Performed cervical screening pap smear Previously. 90% & 93.4% of the nurses, respectively, were unsatisfied with their salary and job. 70% of them had anoccupational stress and 100% Perceived occupational health risks. Conclusion: The great majority of nurses has unsatisfied and job stress. Most of them never Performed pap smear Previously and absolutely refuse to do in future. The main cause for refusing cervical screening as mentioned by nurses was a high flow rate of positive cases

Effect of Time Management Program on Job Satisfaction for Head Nurses

Background:- Time management and job satisfaction all related to each other and greatly affect success of organization.Subjects and Methods:-The study aimed to  evaluate the efficacy of a designed program of time management on job satisfaction for head nurses. A Quasi-experimental design was used for a total number of head nurses participated. Two tools of data collection used, namely, time management knowledge Questionnaire and job satisfaction Questionnaire.Results: There was a significant   response related to head nurse's time waster post program implemented and three quarter of head nurses reported that job satisfaction was moderate levels post  program.  There is highly statistically significant relationship between time management   and job satisfaction.Recommendation: the study recommended that time management training should be held for all hospitals and hospital personnel, especially nurses who tolerate more problems. Keywords: Head nurses, Time management, Job satisfaction, Training program

A Suggested Proposal for Developing the Dimensions of Administrative Transparency and Intellectual Capital Management of Academic Leaders in the Faculties of Preparing Kindergarten Teachers in the Light of some Developed Countries Experiences\u27

The current research aimed at presenting a suggested proposal for developing the dimensions of administrative transparency and intellectual capital management for academic leaders in the faculties of preparing kindergarten teachers in the light of some developed countries experiences\u27. The research utilized the descriptive approach to suit its nature and objectives. For data collection a questionnaire was used- prepared by the researcher- directed to a sample of faculty members and their assistants. The research sample consisted of (60) faculty members and their assistants in the faculties of preparing kindergarten teachers in Universities of (Cairo- Mansours-Minia), in order to diagnose the reality of developing the dimensions of administrative transparency and intellectual capital management for academic leaders in the faculties of preparing kindergarten teachers in the light of some developed countries experiences\u27. The research revealed a set of results; the most significant of which are that the administrative transparency and intellectual capital management has been achieved among academic leaders in the faculties of preparing kindergarten teachers in the light of some developed countries experiences\u27 to moderate degree except for the statements in the axis of administrative transparency which related to (activating the complaints and suggestions boxes), which was achieved below the minimum confidence interval levels, this mainly indicated that it was not achieved. Whereas the statements of (announcing the decisions that govern the faculty\u27s work to achieve the university\u27s goals and publishing real information about the faculty) were achieved to a high degree, which indicated that they were significantly achieved among the Heads of the Departments. In addition to some statements in the axis of intellectual capital management as; (building social networks based on trust, values, and ethics as a stimulator for creativity and innovation) which was achieved significantly among the Heads of the Departments. The research concluded with a suggested proposal for developing the dimensions of administrative transparency and intellectual capital management for academic leaders in the faculties of preparing kindergarten teachers in the light of some developed countries experiences\u27, in addition to providing a set of future studies and research

Effect of metformin on Sirtuin-1 disorders associated with diabetes in male rats

Background: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, hyperinsulinaemia and hyperglycaemia. Increased glucose production through abnormally elevated hepatic gluconeogenesis is central to the manifestation of hyperglycaemia in T2DM. Metformin corrects hyperglycaemia mainly through inhibition of gluconeogenesis. Sirtuin 1 (SIRT1) has been identified as regulator of gluconeogenic gene expression. The present study aimed to evaluate the effect of metformin on SIRT1 level and activity in liver and pancreas of diabetic rats. Further, the possible role of SIRT1 on metabolic disorders associated with diabetes mellitus, including serum levels of glucose, insulin, triglyceride (TG) and high density lipoprotiens (HDL), will be explored.Methods: Thirty-two male albino rats were divided into control group (GpI), diabetic (DM) group (GpII), (metformin + DM) group (GpIII) administered 120 mg/kg metformin daily for 1 month before induction of diabetes, (DM + metformin) group (GpIV) administered 250 mg/kg metformin daily for 1 month after induction of diabetes. At the end of the study, BMI%, serum levels of glucose, insulin, TG and HDL, HOMA, SIRT1 level and activity in liver and pancreas and pancreatic DNA ladder were assessed.Results: Our results showed significant decrease in serum glucose, insulin and TG levels and HOMA; significant increase in HDL level and SIRT1 level and activity in liver and pancreas beside the marked disappearance of pancreatic apoptosis in GpIII & IV relative to GpII. Regarding BMI%, it showed no significant changes in GpIV relative to GpII. No significant change was recorded between GpIII and GpIV regarding all studied parameters except on serum TG.Conclusion: Lowered SIRT1 in diabetes was improved by the administration of Metformin. Consequently, the pathophysiological disorders associated with T2DM were improved.Keywords: DM, Metformin, SIRT1, Pancreatic apoptosi

Low cost detection of hepatitis C virus RNA in HCV infected patients by SYBR Green I real-time PCR

The prevalence of hepatitis C virus (HCV) is highest in Egypt compared to other countries. Nucleic acid amplification test (NAT) allows detection of HCV early during the course of infection. Unfortunately, NAT is more expensive than ELISA, thus its routine use as a screening tool for blood products or in clinical practice is quite limited. The aim of this study was to compare two common RT-PCR methods, TaqMan probe technique and SYBR Green method in quantitative detection of HCV RNA for diagnosis and follow up of HCV patients. Among the recruited 220 HCV patients, 154 (70%) were HCV-RNA positive by both the techniques, while 24 (10.9%) were negative by both techniques. On the other hand, 40 (18.2%) cases were HCV RNA positive only by SYBR Green technique, and 2 (0.9%) only by TaqMan probe technique. Forty (20.4%) of the 196 chronic HCV cases were HCV-RNA positive by SYBR Green but negative by TaqMan probe technique.Conclusion: This method is useful for rapid qualitative detection of HCV infection and particularly suitable for routine diagnostic applications.Keywords: HCV, PCR, SYBR Green 1, TaqMan probe, Viral loa

Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

BACKGROUND: Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. MATERIALS AND METHODS: Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. RESULTS: NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin

The outcome of early-stage glottic carcinoma patients treated with radiotherapy: Egyptian National Cancer Institute (NCI-Egypt) experience

Background: Radiotherapy (RT) is an appropriate treatment option for early-stage glottic cancer (ESGC) that achieves high local control and preserves voice quality. However, the optimal radiation treatment schedule remains unknown. We present our institution's 14-year experience in treating ESGC with definitive radiotherapy between 2005 and 2019 inclusively. Materials and methods: We reviewed the medical records of 104 patients; 63 (60.5%) were treated with conventional fractionation (CF), and 41 (39.5%) were treated with hypofractionated radiotherapy (HF). The clinical T-stage was T1a in 50 patients (48%), T1b in 27 (26%), and T2 in 27 (26%). Age, gender, anterior commissure involvement, stage, radiotherapy technique, radiation fraction size, and overall treatment time (OTT) were analyzed as prognostic factors. The survival outcomes, local regional control (LRC), and laryngeal preservation rate were evaluated. Results: The 5-year overall survival (OS) and LCR were 83.3% and 78%, respectively. On univariate analysis,  treatment with CF (p = 0.02), prolonged OTT > 49 days in CF and > 40 days in HF (p = 0.04), and RT total dose < 66 Gy (p = 0.03) were associated with poor LRC. Multivariate analysis showed a non-significant association with LRC (all p > 0.05). The 5-year OS rate in the CF and HF-treated patients was 84.9% and 72.1%, respectively (p = 0.99), and in patients who had T1a, T1b, and T2 disease, were 78.2%, 96.0%, and 82.1%, respectively (p = 0.43). All patients and tumor variables showed no statistically significant association with OS. Only low-grade acute toxicity was observed. Conclusion: Non-inferiority results supported the HF schedule to ESGC, including high local disease control and decreased overall treatment time. Our study supports its efficacy in the primary care of ESGC with manageable side effects