Syntheses and characterization of water-soluble phythalocyanines for diagnosis and treatment of cancer

Ongarora, Benson Getenga, B.S., Moi University, 2005 Doctor of Philosophy, Fall Commencement, 2012 Major: Chemistry Syntheses and Characterization of Water-Soluble Phthalocyanines for Diagnosis and Treatment of Cancer Dissertation directed by Professor M.Graҫa H. Vicente Pages in dissertation, xi. Words in abstract, 251. ABSTRACT Chapter 1 describes the general properties of phthalocyanines, synthesis of metallo-phthalocyanines, their photophysical features and their uses. The concepts of PDT and targeted therapeutics are also introduced. Chapter 2 describes the syntheses, characterization, photophysical studies and biological evaluation of cationic phthalocyanines. The trimethylaminophenoxy substituted phthalocyanines were synthesized through statistical condensation method, which gave a statistical mixture of isomers. Di-cationic phthalocyanines were found to be more cytotoxic. The amphiphilicity of the phthalocyanines played an important role. Chapter 3 covers the conjugation of phthalocyanines to peptides and is in pursuit of targeted therapeutics. The conjugation of two peptides, EGFR L1 (six amino acid residues) and EGFR L2 (twelve amino acid residues), gave conjugates with different charge, length, and hydrophobicity. The bioconjugates were synthesized via SPS method using typical peptide coupling agents. Cellular and animal studies are described for the conjugates. Chapter 4 is a description of the syntheses and characterization of pure regiomeric phthalocyanines. Previous chapters described, mostly, statistical mixture of Pcs. In this chapter, strategy to the synthesis of monomeric isomers and their characterization is presented. Chapter 5 describes the syntheses, characterization and cellular studies of a series of di-cationic and pegylated phthalocyanines. Statistical condensation was used in the synthesis of macrocycles. Phthalocyanines with cationic charge at close proximity and on α-substitution position of the macrocycle were found to be more cytotoxic. In addition, Pc-antibody bioconjugates are discussed. The biological studies are described for both cationic Pcs and Pc-conjugates. Just like Chapter 3, this chapter is also in pursuit of targeted therapeutics

Banking sector stability, efficiency, and outreach in Kenya

Although Kenya's financial system is by far the largest and most developed in East Africa and its stability has improved significantly over the past years, many challenges remain. This paper assesses the stability, efficiency, and outreach of Kenya's banking system, usingaggregate, bank-level, and survey data. Banks'asset quality and liquidity positions have improved, making the system more resistant to shocks, and interest rate spreads have declined, in part due to reduction in the overhead costs of foreign banks. Outreach remains limited, but has improved in recent years, driven by mobile payments services in the domestic remittance market. Fostering a level regulatory playing field for all deposit-taking institutions is a key remaining challenge. Specifically, an effective but not overly burdensome framework for regulation and supervision of microfinance institutions and cooperatives is a priority. Maintaining an openness to new, and non-bank, providers of financial services, which has enabled the success of mobile payments, could also further outreach.Banks&Banking Reform,Access to Finance,Debt Markets,Emerging Markets,Bankruptcy and Resolution of Financial Distress

Antibiotic resistance in the sediments of a second order stream passing through agricultural farm land: Njoro river, Kenya

A significant proportion of the population living along River Njoro depend on direct river use to carry out domestic activities. Antibiotic pollutants in wastes of treated farm animals that have not undergone any disinfection and sewage treatment processes pose a significant environmental health risk. The current study investigated the presence of total antibiotic resistant bacteria to a range of antibiotics used in the treatment of infectious diseases that may find their way into water and sediments in the river. This was done by culturing samples on nutrient agar media amended with various types of antibiotics. The study showed significant (P< 0.05) spatial variations in total bacteria resistant to chroramphenical, tetracycline, ampicillin and streptomycin antibiotics. Faecal pollution in river Njoro can transmit various diarrhoea pathogens as well as being a reservoir for antibiotic resistant genes that can be transmitted to consumers through water

Effect of Environmental Exposure on the Lead Levels in Human Blood in Kenya

Lead is one of the heavy metals associated with a number of health problems such as abdominal pains, constipation and loss of appetite, nausea, vomiting, insomnia, headache, irritability, dizziness and lead encephalopathy. The major source of lead into the environment is through emission from auto exhaust in countries still using leaded fuel, with other contributors being cigarette smoke, burning of lead battery castings, weathering, ceramic industries and paints. Therefore there is need for continued monitoring of the levels of lead in the environment and in people to determine the level of exposure. The aim of the study was to determine the effect of environmental exposure on the levels of lead in human blood in Nairobi City and Nyamira District, Kenya. The subjects who had lived in the study areas continuously for five years were randomly selected and recruited for the study. The study used a questionnaire to assess lead exposure factors of the recruits, while atomic absorption spectroscopy and differential pulse anodic stripping voltammetry were used for determining the lead levels. The subjects in Nairobi City Centre had the highest mean blood lead (BPb) level of 29.9 + 16.91 µg/l, while Nyamira Rural subjects had the lowest mean of 24.20 + 7.07 µg/l. The mean lead level of the subjects was statistically significant between Nairobi City Centre and Nyamira Rural (P &lt; 0.01, df = 99). The smokers, those who travelled frequently, the users of glazed ceramics, those who worked in industries and those who lived near busy roads had higher levels of blood lead. The study provides an additional data pointing to elevated blood lead levels in environmentally exposed individuals. Keywords: Lead, environmental exposure, human blood, AAS, DPASV.

Effect of Occupation on the Levels of Lead in Human Blood in Kenya

The occupation an individual is involved in exposes him or her to different levels of lead from the work environment. The main occupation of the study subjects included working in the petrol stations, teaching, nursing, street hawking, doing clerical work, working in public vehicles, farming and schooling. The aim of the study was to determine the effect of occupation on the lead levels in human blood in Nairobi City and Nyamira District, Kenya. The subjects involved in the different occupations were randomly selected and recruited for the study. The study used a questionnaire to assess lead exposure factors of the recruits, while atomic absorption spectroscopy and differential pulse anodic stripping voltammetry were used for determining the lead levels. The street hawkers in Nairobi City centre had the highest mean blood lead level of 36.85?16.98 ?g/ dl while the teachers of Nyamira Town had the lowest mean blood lead level of 8.1?5.3 ?g/ dl. The study provides an additional data pointing to elevated blood lead levels in occupationally exposed individuals. Key words: Occupational exposure, BPb, AAS, DPASV

Potential of the filamentous fungus Aspergillus niger AN 400 to degrade Atrazine in wastewaters

This research aims to evaluate the ability of the fungal specie Aspergillus niger AN 400 to metabolize atrazine (ATZ) in model wastewaters, as most of the research with this worldwide used herbicide is focused on bacteria and on soil bioremediation. Firstly, the tolerance of A. niger for ATZ was evaluated in petri dishes. A. niger growth in all the tested ATZ concentrations, up to 30 mg L1. Biodegradation of ATZ was then conducted in batch reactors of 3 L, with dispersed fungal biomass. Reactors were operated for 8 days at different conditions: without glucose (RG0) and glucose at concentrations of 0.5; 1.0; 2.0; 3.0; 4.0 and 5.0 g L1 - RG0.5; RG1; RG2; RG3; RG4 and RG5, respectively. Control (RC) includes a reactor in the absence of fungal spores. The highest ATZ removal, 72%, occurred in RG3. At higher glucose concentration, substrate competition kinetics may be the responsible for the decrease of biodegradation rate constants. Only 50% of Chemical Oxygen Demand (COD) removal was obtained due to the presence of methanol used to dissolve ATZ, which has contributed for most of the COD in reactors. Detoxification of the ATZ solution by the biological treatment was observed by the Allium test.The authors thank CAPES for the PhD scholarships and wich and CNPQ there search productivity grantPQ2(311203/2012-4) and the bagPDE (200444/2014-0). Acknowledges also to the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Luciana Pereira a post-doc fellowship (SFRH/BPD/110235/ 2015) from FCT

Laboratory degradation studies of &sup1;⁴C-atrazine and -isoproturon in soil from sugarcane cultivated fields under Kenyan tropical conditions.

A study to compare the degradation rates of atrazine (6-chloro-N (2)-ethyl-N (4)-isopropyl-1,3,5-triazine-2,4-diammine) and isoproturon [3-(4-isopropylphenyl)-1,1-dimethylurea] in soils from sugarcane fields with different practices of herbicides application was carried out. C-14-atrazine was poorly mineralized to (CO2)-C-14 (1.10% +/- A 0.22%) after 139 days of incubation in soil without previous exposure to atrazine. In the same soil also with no previous isoproturon exposure isoproturon was mineralized to (CO2)-C-14 by 7.70% +/- A 0.94%. Atrazine mineralization after 98 days was 13.4% +/- A 0.30% in soil which discontinued the use of atrazine in 1997 while it was 89.9% +/- A 1.23% in soil in which atrazine is currently being used. The isoproturon mineralization values were 7.24% +/- A 0.85% and 22.97% +/- A 0.96% in soil which discontinued atrazine and soil currently using atrazine, respectively

Study of atrazine degradation in soil from Kenyan sugarcane-cultivated fields in controlled laboratory conditions.

A study to compare the extent of atrazine mineralization in soils from Kenyan sugarcane-cultivated fields with and without history of atrazine use was carried out in the laboratory under controlled conditions. The study was testing the hypothesis that repeated atrazine application to soil will not result in enhanced atrazine mineralization. The study was carried out with 14C-uniformly ring-labeled atrazine in a laboratory under controlled conditions. Atrazine mineralization to 14CO2 in soil with no history of atrazine use was negligible (0.16%) after 163 days of soil incubation. The three metabolites hydroxyatrazine, desisopropylatrazine, and desethylatrazine in the proportion of 17.7%, 1.3%, and 2.6%, respectively, were in the soil after 75 days. In the soil from the sugarcane-cultivated field with history of atrazine use, atrazine mineralization was 89.9% after 98 days. The same soil, amended with mature compost, showed a lag phase of eight days before rapid atrazine mineralization was observed

Atrazine and terbuthylazine mineralization by an Arthrobacter sp. isolated from a sugarcane-cultivated soil in Kenya.

A tropical soil from a Kenyan sugarcane-cultivated field showed a very high capability to mineralize C-14-ring-labeled atrazine. In laboratory experiments this soil mineralized about 90% of the applied atrazine within 98 d. The atrazine-degrading microbial community was enriched in liquid cultures containing atrazine as the sole N source and 100 mg L-1 glucose as additional C source. From the enrichment culture a bacterial strain was isolated and identified by comparative sequence analysis of the 16S-rDNA as member of the genus Arthrobacter. The enriched mixed culture as well as the isolated strain, designated as Arthrobacter sp. strain GZK-1, could grow on atrazine and terbuthylazine as sole N-sources; Arthrobacter sp. GZK-1 mineralized C-14-ring-labeled atrazine up to 88% to (CO2)-C-14 and C-14-ring-labeled terbuthylazine up to 65% to (CO2)-C-14 in a liquid culture within 14 d. The enriched microbial consortium as well as the isolated strain could be a potential solution for the remediation of s-triazine polluted agricultural soils