Synthesis, characterization and biological evaluation of zinc(ii) complexes with phenanthroline derivatives and s-methyl dithiocarbazate schiff bases

Dissertação de mestrado, Inovação Química e Regulamentação (Erasmus Mundus), Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2017The discovery of novel active compounds with new mechanisms of action, higher efficacy and improved selectivity is a matter of urgency to multi drug resistance and toxicity problems associated with many therapeutic drugs. In the current work S-methyl dithiocarbazate Schiff base: SalSmdt, Mp(Smdt)2, VanSmdt, PySmdt and their Zn(II) complexes: Zn[(SalSmdt)(H2O)]0.5H2O, Zn2[(Mp(Smdt)2)(CH3COO)], Zn[(VanSmdt)(H2O)] and Zn[(PySmdt)(CH3COO)]1.5H2O were synthesized. The Schiff bases were obtained by condensation of S-methyl dithiocarbazate (smdt) with different aromatic aldehydes: salicylaldehyde (sal), o-vanillin (van), pyridoxal (py) and 2,6-diformyl-4-methylphenol (Mp). Additionally, Zn[(phen)2(NO3)2]2H2O, Zn[(aminophen)2(NO3)2]1.5H2O and Zn[(Mephen)2(NO3)2]3.5H2O complexes were developed by reaction of Zn(II) with 1,10- phenanthroline (phen), 4,7-dimethyl-1,10-phenanthroline (Mephen) and 5-amino-1,10- phenanthroline (aminophen). All compounds were characterized by elemental analysis, FTIR, UV-Vis, NMR, MS and fluorescence spectroscopies. The characterization suggests that the Schiff base ligands coordinate the metal ion through the phenolate–O, the imine-N and the sulfur atom in the thiol form (except in Zn[(PySmdt)(CH3COO)] for which the thione is proposed). The stability of the compounds in buffered aqueous media (5 % DMSO and 95 % PBS, pH 7.4) was evaluated and all compounds are stable at least for three hours. The antioxidant potential was tested using the 2,2-diphenyl-1-picrylhydrazyl assay. All S-methyl dithiocarbazate Schiff bases showed moderate antioxidant activity but the Zn(II) complexes, with the exception of Zn[(PySmdt)(CH3COO)], are inactive. The Zn-phenanthroline complexes were tested for their DNA binding ability by fluorescence spectroscopy. The results indicate that there is interaction between the complexes and calf thymus DNA. Cytotoxicity studies with several tumor cell lines (PC-3, MCF-7 and CACO-2) are ongoing. The results obtained for the Schiff bases are promising since the IC50 values ranged from 4.41 to 28.99 μM. The phenanthroline ligands and their corresponding Zn complexes showed very high cytotoxicity towards A2780 ovarian cancer cells, with the Zn complexes showing slightly higher activity than the ligands.A descoberta de novos fármacos, com mecanismos de acção alternativos, maior eficácia e selectividade é urgente para combater os problemas associados à resistência e à toxicidade dos fármacos correntes. Neste trabalho bases de Schiff derivadas do S-metil-ditiocarbazato: SalSmdt, Mp(Smdt)2, VanSmdt, PySmdt e os seus complexos de zinco(II) foram sintetizados. As bases de Schiff foram obtidas através da condensação do S-metil-ditiocarbazato (smdt) com diferentes aldeídos aromáticos: salicilaldeído (Sal), o-vanilina (Van) pyridoxal (Py) e 2,6-diformil-4- metilfenol (Mp) em álcoois. Foram também sintetizados os complexos Zn[(phen)2(NO3)2]2H2O, Zn[(aminophen)2(NO3)2]1.5H2O e Zn[(Mephen)2(NO3)2]3.5H2O por reacção do Zn(II) com 1,10-fenantrolina (phen), 4,7-dimetil-1,10-fenantrolina (Mephen) e 5- amino-1,10-fenantolina (aminophen), respectivamente. Todos os compostos foram caracterizados por análise elementar, espectroscopia de FTIR, UV-Vis, RMN, fluorescência e espectrometria de massa. A caracterização sugere que as bases de Schiff coordenam o ião metálico através do O-fenolato, o N-imina e o átomo de enxofre na forma tiol (excepto no Zn[(PySmdt)(CH3COO)] para o qual se propõe o ligando na forma tiona). A estabilidade dos compostos foi avaliada em meio aquoso tamponizado (5 % dmso e 95 % PBS, pH=7.4) tendo-se concluído que todos os compostos são estáveis durante pelo menos 3h. O potencial antioxidante dos compostos foi testado usando um ensaio com 2,2-difenil-1-picrilhidrazil. Todas as bases de Schiff possuem actividade antioxidante moderada, mas os complexos de Zn(II) (excepto o Zn[(PySmdt)(CH3COO)]) são inactivos. Os complexos derivados das fenantrolinas foram testados quanto à sua capacidade para interagir com o ADN usando espectrofotometria de fluorescência e revelaram capacidade, sendo o Zn(aminophen) o mais activo. Encontram-se a decorrer estudos de citotoxidade com várias linhas celulares tumorais (PC-3, MCF-7 e CACO-2). Os resultados das bases de Schiff são promissores, uma vez que os IC50 são da ordem dos μM (entre 4.41 e 28.99). As fenantrolinas e seus correspondentes complexos de Zn(II) mostraram citotoxicidade muito elevada nas células tumorais A2780, com os complexos a revelarem actividade ligeiramente superior aos ligandos

AWARENESS OF OBSTETRIC DANGER SIGNS AND ASSOCIATED FACTORS AMONG PREGNANT WOMEN WHO ATTEND ANTENATAL CARE IN PUBLIC HEALTH INSTITUTIONS OF ADAMA CITY, OROMIA, ETHIOPIA

Improving awareness of women about obstetric danger signs of pregnancy, labor, and postpartum period is the crucial first step in accepting appropriate and timely health care service. In Ethiopia, where pregnancy related complications and maternal death is high, little is known about level of awareness of obstetric danger signs. The aim of this study was to assess Awareness of Obstetric Danger Signs and Associated Factors among Pregnant Women who attend Ante-natal care in Public Health Institutions of Adama City, Oromia, Ethiopia, 2018.Institutional based cross-sectional study was conducted from October 2017 to April 2018 and a total of 381 pregnant women were selected using Systematic random sampling technique. Interviewer administered structured Questionnaire was used to collect data. Data were cleaned and analyzed using EPI-INFO version 7 and SPSS window version 20. Bivariate and multi variable Logistic regression was used to assess association between awareness of obstetric danger signs and various independent variables.A total of 381 pregnant women were participated with 100% response rate. Of all participants about 44.4% knew seven and above obstetric danger signs of pregnancy, labor, and postpartum period. Out of the 381 participants 261 (68.5%), 240 (63%) and 164 (43%) knew at least two danger signs during pregnancy, childbirth and postpartum period, respectively. Vaginal bleeding was the most commonly mentioned danger signs of pregnancy (59.8%), labor (66.1%) and postpartum (60.4%). In multivariate logistic regression analysis, maternal and husband educational status, residence, and sources of obstetric danger signs related information were significantly associated with awareness of obstetric danger signs. Awareness of women about obstetric danger signs of pregnancy, labor, and postpartum period was low and affected by Partner & maternal educational status, sources of obstetric danger signs related information, and residence. Therefore, it needs to raise women’s awareness of danger signs and associated factors through maternal and child health service by designing appropriate strategies including provision of targeted information, education, and communication

Banana Xanthomonas wilt in Ethiopia: Occurrence and insect vector transmission

Bacterial wilt caused by Xanthomonas vasicola pv. musacearum (Xvm) is an important disease of enset and banana in south and south-western Ethiopia where, the diversity of the insect fauna on banana inflorescences was unknown and the role of insects as vectors of the disease had not been studied. The objectives of this study wereto assess the occurrence of bacterial wilt and male bud infection, the diversity of insect families in banana plantations and the presence of the bacteria on insects collected from diseased inflorescences in south and southwestern Ethiopia. Surveys were carried out and insects were collected from three different zones in 2005. The diversity and richness of the insect families was assessed across sites and genotypes and comparisons were made using the Shannon Diversity Index and the Jack knife estimator, respectively. Correlations were made betweenthe abundance and incidence of insects with the incidence of male bud infection on ‘Pisang Awak’ plants. A wide range of insect families were recorded and they varied according to banana genotype and altitude. The Drosophilidae and Apinae families were most frequently recorded across sites and genotypes. The ‘Wendo’ variety (AAACavendish group) had the highest diversity and richness of insect families within and across sites. In contrast to the Kembata Tembaro and Bench Maji zones, severe and widespread male bud infection of banana was found in Kaffa, where there was a high diversity of insects on the ‘Pisang Awak’ and ‘Abesha muz’ plants. The incidenceof male bud infection on ‘Pisang Awak’ plants was highly correlated with the incidence of insects (R2 = 0.964). The incidence of male bud infection however depends on the floral morphology and altitude. Artificial inoculation with Xvm ooze on fresh male bract and flower scars resulted in infections on ‘Pisang Awak’ and ‘Abesha muz’ plants, but the ‘Dwarf Cavendish’ plants with persistent bracts and flowers remained healthy. Few male bud infections were observed at altitudes above 1,700 masl. Xvm was isolated from Apinae, Lonchaeidae, Muscidae,Tephritidae and Vespidae insect families. Lonchaeidae (Silba spp.) were frequently observed on banana bract and flower scars and could thus be an important insect vector of Xvm in Ethiopia

An IPM guide for enset root mealybug (Cataenococcus ensete) in enset production

This guide has been produced as an overview of a body of work that aims to help mitigate the threat of Enset mealybug: the biology and description of Enset mealybug; its behaviour; its geographical distribution; the pest symptoms; the list of mealybug dispersal methods, and the means of mealybug management, including prevention (clean planting material, extension, affordable management, quarantine, hygiene and ant control), cultural control (farmyard manure, hot water treatment, cultivation), biological control, use of insecticidal plant extracts (botanicals), and agrochemical control

Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).</p> <p>Methods</p> <p>In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia.</p> <p>Results</p> <p>The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate.</p> <p>Conclusion</p> <p>In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.</p

Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection

Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO). Methods: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. Results: The proportion of HIV-/TB patients with an increased FeNO level (&gt; 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate. Conclusion: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.Original Publication: Jonna Idh, Anna Westman, Daniel Elias, Feleke Moges, Assefa Getachew, Aschalew Gelaw, Tommy Sundqvist, Tony Forslund, Addis Alemu, Belete Ayele, Ermias Diro, Endalkachew Melese, Yared Wondmikun, Sven Britton, Olle Stendahl and Thomas Schoen, Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection, 2008, BMC INFECTIOUS DISEASES, (8), 146. http://dx.doi.org/10.1186/1471-2334-8-146 Publisher: BioMed Central http://www.biomedcentral.com

Prevalence of and Risk Factors for Trachoma in Oromia Regional State of Ethiopia: Results of 79 Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: To complete the baseline trachoma map in Oromia, Ethiopia, by determining prevalences of trichiasis and trachomatous inflammation - follicular (TF) at evaluation unit (EU) level, covering all districts (woredas) without current prevalence data or active control programs, and to identify factors associated with disease. METHODS: Using standardized methodologies and training developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from December 2012 to July 2014. RESULTS: Teams visited 46,244 households in 2037 clusters from 252 woredas (79 EUs). A total of 127,357 individuals were examined. The overall age- and sex-adjusted prevalence of trichiasis in adults was 0.82% (95% confidence interval, CI, 0.70-0.94%), with 72 EUs covering 240 woredas having trichiasis prevalences above the elimination threshold of 0.2% in those aged ≥15 years. The overall age-adjusted TF prevalence in 1-9-year-olds was 23.4%, with 56 EUs covering 218 woredas shown to need implementation of the A, F and E components of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement) for 3 years before impact surveys. Younger age, female sex, increased time to the main source of water for face-washing, household use of open defecation, low mean precipitation, low mean annual temperature, and lower altitude, were independently associated with TF in children. The 232 woredas in 64 EUs in which TF prevalence was ≥5% require implementation of the F and E components of the SAFE strategy. CONCLUSION: Both active trachoma and trichiasis are highly prevalent in much of Oromia, constituting a significant public health problem for the region

The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015

Soil transmitted helminths and schistosoma mansoni infections among school children in zarima town, northwest Ethiopia

<p>Abstract</p> <p>Background</p> <p>In Ethiopia, because of low quality drinking water supply and latrine coverage, helminths infections are the second most predominant causes of outpatient morbidity. Indeed, there is a scarcity of information on the prevalence of soil transmitted helminths and Schistosomiasis in Ethiopia, special in study area. Therefore, the aim of this study was to determine the prevalence and associated risk factors of soil transmitted helminths and intestinal Schistosomiasis.</p> <p>Methods</p> <p>Cross-sectional study was conducted among 319 school children of Zarima town from April 1 to May 25, 2009. A pre-tested structured questionnaire was used to collect socio-demographic data and possible risk factors exposure. Early morning stool samples were collected and a Kato Katz semi concentration technique was used to examine and count parasitic load by compound light microscope. Data entry and analysis was done using SPSS-15 version and p-value < 0.05 considered statistically significant.</p> <p>Results</p> <p>Out of 319 study subjects, 263 (82.4%) of the study participants infected with one or more parasites. From soil transmitted helminths, <it>Ascaris lumbricoides </it>was the predominant isolate (22%) followed by Hookworms (19%) and <it>Trichuris trichiura </it>(2.5%). <it>Schistosoma mansoni </it>was also isolated in 37.9% of the study participants. Hookworm and <it>S. mansoni infections </it>showed <it>s</it>tatistically significant associations with shoe wearing and swimming habit of school children, respectively.</p> <p>Conclusion</p> <p>Prevalence of soil transmitted helminths (STH) and <it>S.mansoni </it>was high and the diseases were still major health problem in the study area which alerts public health intervention as soon as possible.</p