Cadmium and mercury levels in saudi women and its possible relationship with hypertension

The association between elevated blood pressure and blood cadmium and mercury levels was examined (2001–2002) in 185 Saudi women previously selected for a case-control study of lead and hypertension risk. Blood pressure was measured twice according to the World Health Organization recommendations. Cadmium and mercury were determined with graphite furnace and hydride system-atomic absorption spectrometry, respectively. Mean blood cadmium concentrations were 0.874±0.995 μg/L in hypertensive and 0.785±0.665 μg/L in controls. While blood mercury concentrations for hypertensives and controls were 3.506±3.617 μg/L and 3.687±3.186 μg/L, respectively. Participants were classified according to the median of blood cadmium and mercury levels. After adjustment for potentially confounding variables, the final logistic regression analyses revealed that women with blood cadmium ≥0.627 μg/L were 3.934 times were more likely to be hypertensive than those with blood cadmium levels <0.627 μg/L, although this was marginally significant (p=0.098). This was likely the result of the small number of subjects, resulting in the weak power to detect a strong significant difference between hypertensives and control cases. On the other hand, the final regression model showed no association between hypertension and mercury. However, this finding should not be conclusive because of the inappropriate choice of the biomarker indicator. Nevertheless, our study supports the hypothesis that exposure to cadmium might increase the risk of hypertension.     

Was Rodney Ledward a statistical outlier? Retrospective analysis using routine hospital data to identify gynaecologists' performance

Objectives To investigate whether routinely collected data from hospital episode statistics could be used to identify the gynaecologist Rodney Ledward, who was suspended in 1966 and was the subject of the Ritchie inquiry into quality and practice within the NHS.Design A mixed scanning approach was used to identify seven variables from hospital episode statistics that were likely to be associated with potentially poor performance. A blinded multivariate analysis was undertaken to determine the distance (known as the Mahalanobis distance) in the seven indicator multidimensional space that each consultant was from the average consultant in each year. The change in Mahalanobis distance over time was also investigated by using a mixed effects model.Setting NHS hospital trusts in two English regions, in the five years from 1991-2 to 1995-6.Population Gynaecology consultants (n = 143) and their hospital episode statistics data.Main outcome measure Whether Ledward was a statistical outlier at the 95% level.Results The proportion of consultants who were outliers in any one year (at the 95% significance level) ranged from 9% to 20%. Ledward appeared as an outlier in three of the five years. Our mixed effects (multi-year) model identified nine high outlier consultants, including Ledward.Conclusion It was possible to identify Ledward as an outlier by using hospital episode statistics data. Although our method found other outlier consultants, we strongly caution that these outliers should not be overinterpreted as indicative of “poor” performance. Instead, a scientific search for a credible explanation should be undertaken, but this was outside the remit of our study. The set of indicators used means that cancer specialists, for example, are likely to have high values for several indicators, and the approach needs to be refined to deal with case mix variation. Even after allowing for that, the interpretation of outlier status is still as yet unclear. Further prospective evaluation of our method is warranted, but our overall approach may be potentially useful in other settings, especially where performance entails several indicator variables.     

Enzymatic,metabolic and secretory perturbations in pancreatic islets of thyroidectomized rats

In thyroidectomized rats, the activity of FAD-linked glycerophosphate dehydrogenase was severely diminished in liver homogenates but not affected significantly in pancreatic islet homogenates, whilst the activity of 2-ketoglutarate dehydrogenase was decreased modestly in both liver and islet homogenates. Likewise, in intact islets of thyroidectomized rats, the generation of³HOH from [2-³H]glycerol was not decreased, and the ratio between oxidative and total glycolysis not significantly lower than in islets from sham-operated rats, at least in the presence of a high concentration of D-glucose. Nevertheless impaired oxidation of both D-[3,4-¹⁴C]glucose and D-[6-¹⁴C]glucose was observed in islets of thyroidectomized rats, the relative magnitude of such a decrease being more pronounced at a low than at a high D-glucose concentration. Such metabolic anomalies coincided with a lower level of plasma insulin and a decreased output of insulin by islets incubated at low (2·8 mM ), but not higher, concentrations of D-glucose. It is concluded that hypothyroidism does not mimic the deficiency in islet FAD-linked glycerophosphate dehydrogenase activity found in rats with inherited or acquired non-insulin-dependent diabetes.     

Factors Associated with Four or More Antenatal Care Visits and Its Decline among Pregnant Women in Tanzania between 1999 and 2010

In Tanzania, the coverage of four or more antenatal care (ANC 4) visits among pregnant women has declined over time. We conducted an exploratory analysis to identify factors associated with utilization of ANC 4 and ANC 4 decline among pregnant women over time. We used data from 8035 women who delivered within two years preceding Tanzania Demographic and Health Surveys conducted in 1999, 2004/05 and 2010. Multivariate logistic regression models were used to examine the association between all potential factors and utilization of ANC 4; and decline in ANC 4 over time. Factors positively associated with ANC 4 utilization were higher quality of services, testing and counseling for HIV during ANC, receiving two or more doses of SP (Sulphadoxine Pyrimethamine)/Fansidar for preventing malaria during ANC and higher educational status of the woman. Negatively associated factors were residing in a zone other than Eastern zone, never married woman, reported long distance to health facility, first ANC visit after four months of pregnancy and woman''s desire to avoid pregnancy. The factors significantly associated with decline in utilization of ANC 4 were: geographic zone and age of the woman at delivery. Strategies to increase ANC 4 utilization should focus on improvement in quality of care, geographic accessibility, early ANC initiation, and services that allow women to avoid pregnancy. The interconnected nature of the Tanzanian Health System is reflected in ANC 4 decline over time where introduction of new programs might have had unintended effects on existing programs. An in-depth assessment of the recent policy change towards Focused Antenatal Care and its implementation across different geographic zones, including its effect on the perception and understanding among women and performance and counseling by health providers can help explain the decline in ANC 4.     

Potential Role of Notch Signalling in CD34+ Chronic Myeloid Leukaemia Cells: Cross-Talk between Notch and BCR-ABL

Notch signalling is critical for haemopoietic stem cell (HSC) self-renewal and survival. The role of Notch signalling has been reported recently in chronic myeloid leukaemia (CML) – a stem cell disease characterized by BCR-ABL tyrosine kinase activation. Therefore, we studied the relationship between BCR-ABL and Notch signalling and assessed the expression patterns of Notch and its downstream target Hes1 in CD34⁺ stem and progenitor cells from chronic-phase CML patients and bone marrow (BM) from normal subjects (NBM). We found significant upregulation (p<0.05) of Notch1, Notch2 and Hes1 on the most primitive CD34⁺Thy⁺ subset of CML CD34⁺ cells suggesting that active Notch signalling in CML primitive progenitors. In addition, Notch1 was also expressed in distinct lymphoid and myeloid progenitors within the CD34⁺ population of primary CML cells. To further delineate the possible role and interactions of Notch with BCR-ABL in CD34⁺ primary cells from chronic-phase CML, we used P-crkl detection as a surrogate assay of BCR-ABL tyrosine kinase activity. Our data revealed that Imatinib (IM) induced BCR-ABL inhibition results in significant (p<0.05) upregulation of Notch activity, assessed by Hes1 expression. Similarly, inhibition of Notch leads to hyperactivation of BCR-ABL. This antagonistic relationship between Notch and BCR-ABL signalling was confirmed in K562 and ALL-SIL cell lines. In K562, we further validated this antagonistic relationship by inhibiting histone deacetylase (HDAC) - an effector pathway of Hes1, using valproic acid (VPA) - a HDAC inhibitor. Finally, we also confirmed the potential antagonism between Notch and BCR/ABL in In Vivo, using publically available GSE-database, by analysing gene expression profile of paired samples from chronic-phase CML patients pre- and post-Imatinib therapy. Thus, we have demonstrated an antagonistic relationship between Notch and BCR-ABL in CML. A combined inhibition of Notch and BCR-ABL may therefore provide superior clinical response over tyrosine-kinase inhibitor monotherapy by targeting both quiescent leukaemic stem cells and differentiated leukaemic cells and hence must be explored.     

Polyesters Based on Linoleic Acid for Biolubricant Basestocks: Low-Temperature,Tribological and Rheological Properties

Presently, plant oils which contain high percentage of linoleic acid 1 are perceived to be a viable alternative to mineral oil for biolubricant applications due to their biodegradability and technical properties. In order to get biodegradable lubricant, triester derivatives compounds (1–5) were synthesized and characterized. The processes involved were monoepoxidation of linoleic acid 2, oxirane ring opening 3, esterification 4 and acylation 5. The structures of the products were confirmed by FTIR, ¹H and ¹³C-NMR and LC-MS. The results that showed lowest temperature properties were obtained for triester 5, with a pour point value (PP) of -73°C, highest onset temperature (260°C) and lowest volatility at 0.30%. Viscosity index (VI) increased for the ester’s synthetic compounds (2, 3, 4, 5), while the PP decreased. This behavior is the result of the increase of the chain length of the branching agents. Triester based linoleic acid has improved properties such as low-temperature and tribological properties. These results will make it feasible for plant oil to be used for biolubricants, fuels in chain saws, transmission oil and brake fluid.     

A novel pH sensitive water soluble fluorescent nanomicellar sensor for potential biomedical applications

Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide–rhodamine bichromophoric FRET system (RNI) to the PMMA block of a well-defined amphiphilic diblock copolymer—poly(methyl methacrylate)–b-poly(methacrylic acid) (PMMA₄₈–b-PMAA₂₇). The RNI-PMMA₄₈–b-PMAA₂₇ adduct is capable of self-assembling into micelles with a hydrophobic PMMA core, containing the anchored fluorescent probe, and a hydrophilic shell composed of PMAA block. Novel fluorescent micelles are able to serve as a highly sensitive pH probe in water and to internalize successfully HeLa and HEK cells. Furthermore, they showed cell specificity and significantly higher photostability than that of a pure organic dye label such as BODIPY. The valuable properties of the newly prepared fluorescent micelles indicate the high potential of the probe for future biological and biomedical applications.