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Pharmacogenetics: The Scientific Basis

The oestrogen effect of soyprotein on female rabbits, fed for a period of 6 weeks, was investigated. Results indicate significant increase ( P r =0.808, P P P P

The discovery of the novel thermal cyclization of enediyne molecules within the\ud Parsons group during studies directed towards the total synthesis of lactonamycin has\ud stimulated an intense research into the cyclization of the enediynes.\ud In this research different functionalised enediynes were synthesised to investigate:-\ud (i) the scope and limitations of the thermal cyclization reactions,\ud (ii) the proposed biradical mechanism for the cyclization reactions,\ud (iii) the intermolecular trappings of the proposed biradical, and\ud (iv) the effect of sterically demanding groups on the rate of cyclization.\ud In the process of testing these objectives, we have been able to synthesize highly\ud functionalised heterocyclic rings by simple thermal cyclization reactions without using\ud any metal catalyst. We have discovered that the cyclizations may have involved free\ud radical mechanism or an ene reaction, followed by a Diels – Alder cycloaddition\ud reactions. Interestingly the cyclised compound 2.1 shows two stereogenic centres at C2\ud and C4 with an absolute configuration of R and S respectively. An in-depth exploration\ud of the stereochemistry of these reactions may increase their application in controlling\ud the stereochemistry of ring systems through simple metal free thermal cyclization\ud reactions. Confirmation of the specific mechanism constitutes an ongoing research\ud within the Parsons group. Conclusively cyclization of highly functionalised enediynes\ud had been proved to be a versatile route to the synthesis of diverse heterocyclic\ud compounds. The ease of cyclizations of a majority of the enediynes in this study has\ud shown that functionalisation and diversification of the core enediyne systems could be\ud utilized in the synthesis of pharmaceutically important antitumour drugs.

Activities of human hepatic drug metabolizing enzymes N-acetyl transferase (NATS) had earlier been recognized as a cause of inter-individual variation in the metabolism of drugs. Therefore acetylation of many drugs in human exhibit genetic polymorphism. The aim of the study was to investigate if acetylator status predispose diabetic mellitus patients more to the complications of renal disease, One hundred and twenty (120) diabetics consisting of (50) Type 1 (T(1)) and 70 Type 2 (T(2)) diabetes mellitus patients and 100 healthy individuals as controls were classified as slow or rapid acetylator using sulphamethazine (SMZ) as an in vivo probe. The percentage acetylation, recovery of SMZ, creatinine clearance and presence of urinary albumin were determined. A significant difference (P 0.05) was observed in the percentage of SMZ acetylated between slow and rapid acetylators in control, T(1) and T(2) subjects. The ratios of slow to rapid acetylators for T(1), T(2) and control subjects were 1:4, 3:2 and 2:3 respectively. No significant differences were observed in the percentage of SMZ recovered in the urine of slow and rapid acetylators that are diabetics. The difference in creatinine clearance of slow and rapid acetylators in T(1) and T(2) were significant (P 0.05). 29% out of 120 (24.2%) diabetics (T(1) and T(2)) exhibited albuminuria out of which 25 (86.2%) had slow acetylator status. These findings suggest that slow acetylator status in diabetes mellitus could be a predisposing factor in the development of renal complications. This underscores the need for a rapid pharmacogenetic testing and therapeutic drug monitoring in such patients. However this inference could be further validated with a larger sample size.

Laboratory measurements of mercury oxidation during selective catalytic reduction (SCR) of nitric oxide, simulation of pilot-scale measurements of mercury oxidation and adsorption by unburned carbon and fly ash, and synthesis of new materials for simultaneous oxidation and adsorption of mercury, were performed in support of the development of technology for control of mercury emissions from coal-fired boilers and furnaces. Conversion of gas-phase mercury from the elemental state to water-soluble oxidized form (HgCl{sub 2}) enables removal of mercury during wet flue gas desulfurization. The increase in mercury oxidation in a monolithic V{sub 2}O{sub 5}-WO{sub 3}/TiO{sub 2} SCR catalyst with increasing HCl at low levels of HCl (< 10 ppmv) and decrease in mercury oxidation with increasing NH{sub 3}/NO ratio during SCR were consistent with results of previous work by others. The most significant finding of the present work was the inhibition of mercury oxidation in the presence of CO during SCR of NO at low levels of HCl. In the presence of 2 ppmv HCl, expected in combustion products from some Powder River Basin coals, an increase in CO from 0 to 50 ppmv reduced the extent of mercury oxidation from 24 {+-} 3 to 1 {+-} 4%. Further increase in CO to 100 ppmv completely suppressed mercury oxidation. In the presence of 11-12 ppmv HCl, increasing CO from 0 to {approx}120 ppmv reduced mercury oxidation from {approx}70% to 50%. Conversion of SO{sub 2} to sulfate also decreased with increasing NH{sub 3}/NO ratio, but the effects of HCl and CO in flue gas on SO{sub 2} oxidation were unclear. Oxidation and adsorption of mercury by unburned carbon and fly ash enables mercury removal in a particulate control device. A chemical kinetic mechanism consisting of nine homogeneous and heterogeneous reactions for mercury oxidation and removal was developed to interpret pilot-scale measurements of mercury oxidation and adsorption by unburned carbon and fly ash in experiments at pilot scale, burning bituminous coals (Gale, 2006) and blends of bituminous coals with Powder River Basin coal (Gale, 2005). The removal of mercury by fly ash and unburned carbon in the flue gas from combustion of the bituminous coals and blends was reproduced with satisfactory accuracy by the model. The enhancement of mercury capture in the presence of calcium (Gale, 2005) explained a synergistic effect of blending on mercury removal across the baghouse. The extent of mercury oxidation, on the other hand, was not so well described by the simulation, because of oversensitivity of the oxidation process in the model to the concentration of unburned carbon. Combined catalysts and sorbents for oxidation and removal of mercury from flue gas at low temperature were based on surfactant-templated silicas containing a transition metal and an organic functional group. The presence of both metal ions and organic groups within the pore structure of the materials is expected to impart to them the ability to simultaneously oxidize elemental mercury and adsorb the resulting oxidized mercury. Twelve mesoporous organosilicate catalysts/sorbents were synthesized, with and without metals (manganese, titanium, vanadium) and organic functional groups (aminopropyl, chloropropyl, mercaptopropyl). Measurement of mercury oxidation and adsorption by the candidate materials remains for future work.

Giroux (2003) indicated that the prison industry has become a major economic industry with many states spending more money on prison reforms than on educational reforms. Juvenile delinquent behavior should be punished but fair treatment and equal rights for all human beings under the rule of law is paramount to punishment. Casella (2001) indicated that the prison population has sky-rocketed, and by 1995 forty-eight states passed laws to facilitate the prosecution of juveniles as adults and therefore children are placed in adult prisons where they are at a higher risk of not only attack and rape, but of suicide. The research established a rationale for restorative justice discipline as an alternate to punitive retributive discipline in order to potentially decrease the number of youth offenders facing incarceration. Crime control is the responsibility of all citizens not just the government and this responsibility reflects the foundational tenets of restorative justice. Bazemore and Umbreit (1995) suggested that restorative justice is not an alternative to punishment it is an alternate punishment to bad or unwanted behavior. A qualitative case study was used to analyze and explore the disciplinary functions and procedures of the Metro County Juvenile Court Community Restorative Boards. The perceptions of two board members and three juvenile court officials was analyzed in an effort to better understand how and why Community Restorative Boards implement restorative justice discipline toward youth offenders. Data were gathered through narrative interviews and participatory observations in order to better understand the emerging phenomenon of restorative discipline within the juvenile justice system as an alternate to punitive retributive discipline. The study analyzed the dynamics of the school to prison pipeline through zero tolerance school policies, examined the juvenile justice system and the sentencing of youth offenders in criminal court. The study also examined the usage of traditional retributive discipline and restorative discipline within the juvenile court system. The study provided empirical data that support the infusion of a complimentary or supplementary restorative justice disciplinary approach toward adjudicating youth offenders within the juvenile court system. Bazemore and Umbreit (1995) suggested that utilizing a restorative justice disciplinary model increases the opportunity for young people to be held accountable for their misbehavior by actively participating in the process of establishing consequences to help repair the harm that they have caused to an individual, the community, and themselves.

This investigation was undertaken to study the distribution and availability of Zn in different soil fractions. The proportions of total Zn present in the soils in exchangeable, organically bound, complexed or adsorbed and residual fractions were determined by sequential extraction with CaCl2, H2O2, EDTA and HCl/HNO3, respectively. Most of the total Zn was, on average, present in the EDTA-Zn (15.5%) and HCl/HNO3-Zn (78%) forms. The CaCl2-Zn and H2O2-Zn fractions averaged 5.0 and 1.5% of the total Zn respectively. Zinc present in exchangeable (CaCl2-Zn), organically bound (H2O2-Zn) and complexed (EDTA-Zn) forms was closely related to the bioavailability of Zn to maize plants grown on these soils. The residual Zn (HCl/HNO3-Zn) was not readily available.

The study investigated the effect of chronic tea intake (1.76g/kg bwt/ day/ rat for 42 days) on blood pressure, body weight and blood lipid profile (total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol and low density lipoprotein (LDL)-cholesterol levels). At the end of the study, the tea-treated rats (n=6) had lower systolic (102.8±1.9 c.f. 111.8± 1.6mmHg; P NQJHM Vol. 15 (1) 2005: pp. 38-41

Animal studies have shown that steroid sex hormones such as estrogen may be helpful in the regulation of several pathophysiologic stages that are involved in wound healing. This study therefore investigated the effects of topical estradiol on wound healing and haemato-biochemical changes in West African dwarf (WAD) goats. Ten WAD goats were used for the study and randomly divided into two equal groups of five animals each; the first group served as the control while the second group was treated topically with estrogen. Healing process was compared between the two groups, haematology and serum biochemistry werecarried out at each phases of the healing process. The result showed significant improved wound contractions in the estrogen treated by day 12, 15 and 17. Haematology and serum analyses revealed significantly (P

The civil engineering industry world-wide has long known that the Conventional Bill of Quantities (BOQ) is inadequate conceptually and functionally. Moreover, the only alternative to it, the Method-Related BOQ (MR Bill), is only marginally better; its development having been constrained by inadequate analysis, problems of inertia attached to current practice, and lack of scientific methodology for the evaluation of comparative performances of alternative prototype forms of BOQ. An analysis and evaluation of the two forms of Bill and of six newly established others, using a newly developed scientific methodology based on worth assessment, statistics, and simulation, is presented. A suitable form of Bill, which is logical and in conformity with the principles of the Measurement Contract with Quantities, has emerged and is recommended to the industry.

In most rural settlements in Nigeria, access to clean and potable water is a great challenge, resulting in water borne diseases. The aim of this study was to assess the levels of some physical, chemical, biochemical and microbial water quality parameters in twelve hand – dug wells in a typical rural area (Igbora) of southwest region of the country. Seasonal variations and proximity to pollution sources (municipal waste dumps and defecation sites) were also examined. Parameters were determined using standard procedures. All parameters were detected up to 200 m from pollution source and most of them increased in concentration during the rainy season over the dry periods, pointing to infiltrations from storm water. Coliform population, Pb, NO 3- and Cd in most cases, exceeded the World Health Organization recommended thresholds for potable water. Effect of distance from pollution sources was more pronounced on fecal and total coliform counts, which decreased with increasing distance from waste dumps. The qualities of the well water samples were therefore not suitable for human consumption without adequate treatment. Regular monitoring of groundwater quality, abolishment of unhealthy waste disposal practices and introduction of modern techniques are recommended.

The study investigated the effect of chronic tea intake (1.76g/kg bwt/ day/ rat for 42 days) on blood pressure, body weight and blood lipid profile (total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol and low density lipoprotein (LDL)-cholesterol levels). At the end of the study, the tea-treated rats (n=6) had lower systolic (102.8±1.9 c.f. 111.8± 1.6mmHg; P NQJHM Vol. 15 (1) 2005: pp. 38-41

No Abstract. Discovery and Innovation Vol. 17(1&2) 2005: 85-93

Field trials were conducted for three years to determine the effects of source, rate and method of application of nitrogen fertilizer on maize yield at Ilora in the derived savanna zone and Ogbomoso in the southern guinea savanna zone of Nigeria. The nitrogen fertilizers (Granulated urea, Regular urea and Calcium Ammonium Nitrate) tested were at 0, 50, 100 and 150 kg N/ha. The methods of fertilizer application used were banded covered and banded uncovered. Results showed that, there were no significant differences in yields obtained from the fertilizers applied. Likewise, the methods of fertilizer application were not significantly different from each other. However, the rates of nitrogen fertilizer applied produced significant differences in maize yields at both locations and nitrogen content in maize leaf tissue at the two locations. Application of 100 kg N/ha produced optimum grain yield and nitrogen content in the ear leaf tissue. The use of granulated urea would be a better choice out of the other nitrogen fertilizers due to its better handling (physical) properties, high nitrogen level and availability. Key Words: Nitrogen sources; nitrogen rate; application methods; maize yield Moor J. Agric. Res. Vol.4(1) 2003:19-25

The study was designed to investigate the effect of chronic tea consumption (1.76g/kg b wt/day/rat for 42 days) on blood pressure (BP), heart rate (HR) and cardiovascular responses to bilateral carotid occlusion (BCO), coupled with some associated mechanisms. Five experiments were performed in paired weight matched groups of rats (n = 5). In the first experiment, group 2 (kept on normal feed; NF and tea drink) had lower systolic, diastolic and mean arterial pressure (MAP) (P < 0.005) compared with group 1 (kept on NF and normal drinking water), with little change in HR and cardiovascular reflex. Experiments 2 to 5 were used to investigate some mechanisms responsible for the hypotensive effect of tea using appropriate pharmacologic blockers. In experiment 2, group 3 (kept on NF and furosemide solution) had similar BP as group 4 (kept on furosemide, NF and tea). In experiment 3, group 5 (kept on NF and captopril solution) had similar BP as group 6 (kept on captopril, NF and tea). In experiment 4, group 7 (kept on NF and nifedipine solution) had similar BP as group 8 (kept on nifedipine, NF and tea). In experiment 5, group 9 (kept on NF and indomethacin solution) also had similar BP as group 10 (kept on indomethacin, NF and tea). The results suggest that chronic tea consumption lowers BP in rats with little change in HR and cardiovascular reflex. The hypotensive effect of tea may be attributed to the following mechanisms: the prostanoids, sodium/potassium transport, calcium transport and the RAS (producing the least contribution). KEY WORDS: Blood pressure (BP), heart rate (HR), rats, tea. Nigerian Journal of Health and Biomedical Sciences Vol.3(2) 2004: 131-135

The human major histocompatibility complex (MHC) class I chain-related gene A (MICA), located 46 kb centromeric to HLA-B, encodes a stress-inducible protein, which is a ligand for the NKG2D receptor. In addition to its primary role in immune surveillance, data suggest that MICA is involved in the immune response to transplants and in susceptibility to some diseases. In this study, 152 subjects from the Yoruba (n=74), Efik (n=32), and Igbo (n=46) tribes of southern Nigeria, 39 nationwide African-American stem cell donors, and 60 African-American individuals residing in the metropolitan Boston area were studied for MICA, HLA-B allelic variation, haplotypic diversity, and linkage disequilibrium (LD). MICA and HLA-B exhibited a high degree of genetic diversity among the populations studied. In particular, MICA allele and HLA-B-MICA haplotype frequencies and LD in the Efik and Igbo tribes were significantly different from the other study groups. HLA-B and MICA loci demonstrated significant global LD in all five populations (P-values &

This study was designed to assess the risks and uncertainties encountered by poultry farmers in Kwara State, Nigeria. Specifically, the study describes the socio-economic characteristics of the farmers, identify the risks and uncertainties encountered by the farmers, determines the level of severity of the risks and uncertainties, and identifies the coping strategies employed by the farmers. Primary data obtained from 99 registered poultry farmers selected through multistage sampling technique were used for the study. These were complemented with data from published and grey literature. Descriptive statistics and 3-point Likert scale were used to analyze the data. The study shows that poultry farming in the study area is practiced mainly by young, small-scale farmers, who are married, with high level of formal education but had little access to extension services. The major sources of risks encountered by the farmers were severe weather fluctuation, lack of veterinary services, disease outbreak, transportation problems, parasites and severe price fluctuation of birds. The study further revealed that the severe risks encountered by the farmers were disease outbreak, poor parent stock, accumulation of dung, severe weather fluctuation, lack of veterinary services and transportation problems. The study therefore calls for improved extension services, good transportation facilities, adequate veterinary services, market information by government and relevant stakeholders as well as formation of cooperative socities by the farmers.

Carboxyhaemoglobin (COHb) concentrations were determined by differential spectrophotometry in blood of 60 healthy adult subjects from various locations in Lagos. Half of these were either occasional or regular tobacco cigarette smokers. Our findings showed that the Lagos dweller has elevated COHb concentration ranging between 7.6%-9.9%, several folds higher than permitted by Air Quality Standards. The range and scatter of COHb in smokers were wider (7.4%-13.0%) than in non smokers. In particular, COHb concentrations were significantly higher in regular smokers than in non smokers by Fisher's exact test (p0.0006). Elevated COHb concentrations among smokers were related to frequency of tobacco use (p0.01). There was however no statistically significant difference in COHb concentrations when the regular and occasional smokers were taken as a group and compared with the non smokers. Haematocrit measurements showed that a degree of anaemia was present in most of the subjects tested irrespective of smoking status (mean packed cell volume = 36.1). It is inferred from this data that the Lagos dweller has high ambient concentrations of COHb and that these may be further aggravated by cigarette smoking.

HLA-A, B and C antigens were determined in 101 healthy subjects from two major and several minor ethnic groups in some parts of Southern Nigeria. Compared to earlier data based on a panel of expatriate Nigerians, significant differences were observed in antigen phenotype and gene frequencies particularly at the HLA-A locus. At least three antigenic specificities not previously observed in the expatriate Nigerians were detected in the present study. These included HLA-B8. B14 and CW1. These antigens however occurred at low frequencies. The antigens A23 and B7 were in positive linkage disequilibrium along with others which involved CW4 with B53 or B35. It is concluded from our findings that HLA polymorphisms in Nigerians may not be completely reflected in major population group studies alone. It is possible that more specificities may be detected by continued testing of the minor ethnic groups. The importance of this could be immense in disease association studies involving HLA genes as well as in anthropology.

OZET AMAC: Tum tuberkuloz vakalarini tariyacak tek bir tani yontemi yoktur. Bu nedenle tani birkac gun veya hafta surebilir, pahali, invazif ve karmasiktir. YONTEM: Ibadan, Nijerya’da Jericho Gogus klinigi’nde takip edilen 100 klinik tanili almis tuberkuloz hastasi (Deney grubu) ve tuberkulozu olmayan 100 saglikli kisi (Kontrol grubu) calismaya alindi. Immun kromatografik stripler uzerinde hareketsizlestirilmis antijenlere dayanan hizli serolojik test kontrol ve deney grubundaki tum deneklere uygulandi. Kontroller klinik muayene ve rie grafi, mikroskopi ve bakteri kulturu yapilarak secildi. Tuberkuloz hastalarinin da pozitifligi ayni sekilde dogrulandi. BULGULAR: Gercek pozitif sayisi 78 (%78) ve yanlis positif sayisi 8 (%8) iken gercek negatifler 92 (%92) ve yanlis negatifler 22 (%22) idi. Serolojik yontemin sensitivite, spesifite, negatif prediktif deger ve positif prediktif degerleri sirasiylasoyleydi: %78,0, %92,0, %80,7 ve %90,7. SONUC: Bu sonuclar serolojik yontemi tani ve ozellikle fakir ve gelismekte olan ulkelerde tuberkulozun idaresi noktasinda rutin uygulamaya sokmak icin dusuktur. Ayrica, hizli serolojik tani icin coklu antijene dayali immunkromatografik kitlerin daha fazla umut verici oldugu soylenebilir.

Nigeria is an exemplar of the challenges of achieving sustainable development in the paradoxical twin realities of resource endowment and acute inequalities originated by difficulties of governance. The paper empirically demonstrates the role of corporate social responsibility (CSR) in facilitating the resolution of this paradox. In its several forms, CSR permeates the industry. The industry deploys CSR as a form of social licence to gain and retain acceptability by its host communities. Previous studies of CSR in the oil and gas industry in Nigeria have focussed solely on multinational operators and their activities, particularly the Nigerian outlet of Royal Dutch Shell, in the Niger Delta region. The present study differs from previous studies by including a significant number of small and medium enterprises trading in the industry, both in and outside of the Niger Delta region and both in the upstream and downstream sectors of the industry.

Background There had been conflicting reports with levels of markers of iron metabolism in HIV infection. This study was therefore aimed at investigating iron status and its possible mediation of severity of HIV- 1 infection and pathogenesis. Method Eighty (80) anti-retroviral naive HIV-1 positive and 50 sero-negative controls were recruited for the study. Concentrations of serum total iron, transferrin, total iron binding capacity (TIBC), CD4+ T -lymphocytes, vitamin C, zinc, selenium and transferrin saturation were estimated. Results The mean CD4+ T-lymphocyte cell counts, serum iron, TIBC, transferrin saturation for the tests and controls were 319 ± 22, 952 ± 57 cells/μl (P < 0.001), 35 ± 0.8, 11.8 ± 0.9 μmol/l (P < 0.001), 58.5 ± 2.2, 45.2 ± 2.4 μmol/l (P < 0.005) and 68.8 ± 3.3, 27.7 ± 2.2%, (P 4+ T-lymphocyte cell count had a positive correlation with levels of vitamin C (r = 0.497, P < 0.001), zinc (r = 0.737, P < 0.001), selenium (r = 0.639, P < 0.001) and a negative correlation with serum iron levels (r = −0.572, P < 0.001). Conclusion It could be inferred that derangement in iron metabolism, in addition to oxidative stress, might have contributed to the depletion of CD4+ T cell population in our subjects and this may result in poor prognosis of the disease.