Boronic Acid Derivatives Targeting HIV-1

A series of novel boronic acid derivatives containing either a pyrimidine or purine base was synthesized. The preparation involved the condensation of 4-bromobutyl boronic acid with the appropriate base. These acyclic nucleosides were designed as potential antiviral agents especially targeting the human immunodeficiency virus. Two analogues, 6-chloro-9-(4-dihydroxyborylbutyl)purine and 2,6-dichloro-9-(4-dihydroxyborylbutyl)purine, exhibited EC50 values of 7.7 µM and 0.99 µM, respectively, in an HIV-1 syncytial plaque reduction assay

Secondary education reform in Lesotho and Zimbabwe and the needs of rural girls: Pronouncements, policy and practice

Analysis of the educational needs of rural girls in Lesotho and Zimbabwe suggests a number of shortcomings in the current form of secondary education, and ways in which it might be modified so as to serve this sizeable group of students better. Several of the shortcomings, notably in relation to curricular irrelevance and excessive focus on examinations, have long been recognised, including by politicians. Yet political pronouncements are seldom translated into policy, and even where policy is formulated, reforms are seldom implemented in schools. This paper makes use of interviews with educational decision-makers in the two southern African countries and a range of documentary sources to explore why, despite the considerable differences between the two contexts, much needed educational reforms have been implemented in neither

Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review

Toy M, Önder FO, Wörmann T, et al. Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review. BMC infectious diseases. 2011;11(1): 337.BACKGROUND: To provide a clear picture of the current hepatitis B situation, the authors performed a systematic review to estimate the age- and region-specific prevalence of chronic hepatitis B (CHB) in Turkey. METHODS: A total of 339 studies with original data on the prevalence of hepatitis B surface antigen (HBsAg) in Turkey and published between 1999 and 2009 were identified through a search of electronic databases, by reviewing citations, and by writing to authors. After a critical assessment, the authors included 129 studies, divided into categories: 'age-specific'; 'region-specific'; and 'specific population group'. To account for the differences among the studies, a generalized linear mixed model was used to estimate the overall prevalence across all age groups and regions. For specific population groups, the authors calculated the weighted mean prevalence. RESULTS: The estimated overall population prevalence was 4.57, 95% confidence interval (CI): 3.58, 5.76, and the estimated total number of CHB cases was about 3.3 million. The outcomes of the age-specific groups varied from 2.84, (95% CI: 2.60, 3.10) for the 0-14-year olds to 6.36 (95% CI: 5.83, 6.90) in the 25-34-year-old group. CONCLUSION: There are large age-group and regional differences in CHB prevalence in Turkey, where CHB remains a serious health problem

Changes in the Circadian Rhythm in Patients with Primary Glaucoma

Purpose The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI). Methods The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients’ intraocular pressure (IOP) and impairment of visual field (VF) were also studied. Results 92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ2-test, P>0.05). Conclusions The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP

Response of human HT-29 colorectal tumor cells to extended exposure to bromodeoxyuridine

Effects of the extended exposure of a human colorectal tumor-cell line (HT-29) to bromodeoxyuridine (BrdUrd) were studied in anticipation of the clinical use of that agent to treat colorectal cancer, particularly as a regionally delivered radiosensitizer. We found that 72-h exposure to a concentration of BrdUrd that is estimated to be locally maintained in the liver (100 μ M ) was significantly cytotoxic with a 3-log reduction in survival. As measured by GC/MS-SIM method, incorporation of BrdUrd into DNA followed an unexpected time course in that continuous exposure to 10 μ M BrdUrd resulted in maximal incorporation at 3 days, after which the extent of incorporated analog fell significantly (despite daily changes of the medium). This finding was apparently due to a greater rate of loss of BrdUrd from the medium at later time points. Flow cytometric analysis using an anti-BrdUrd antibody (IU-4) revealed that antibody binding also peaked and fell off with time. However, at exposure times of >24 h, the timing and extent of this decline were significantly different than had been indicated by the GC/MS method. These results indicate that the quantitative relationship between antibody staining and BrdUrd incorporation changes as drug-exposure time increases and that quantitative studies of anti-BrdUrd antibody binding must be interpreted with caution, especially when extended drug-treatment protocols have been used.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46921/1/280_2004_Article_BF00694337.pd