New developments in telomere length analysis

Telomeres provide an essential 'capping' function, which prevents the natural end of a chromosome from being recognised as a simple dsDNA break. The biology of human telomeres is inextricably linked with both cancer and ageing. As such there is considerable interest in determining the length of these essential and dynamic structures. Here I review, from the standpoint of ageing research in humans, the current situation with regards to technologies available to determine telomere length in human cells and tissues.     

Pressure garments for use in the treatment of hypertrophic scars -- an evaluation of current construction techniques in NHS hospitals

The purpose of this investigation was to establish the variety of pressure garment construction methods and materials used in UK hospitals. This paper reports an investigation conducted in two parts. First, a survey of pressure garment practitioners was conducted and second, 15 of the fabrics currently used in UK hospitals were tested. The results showed that the pressures exerted by pressure garments constructed in UK hospitals were likely to range from ineffectively low to dangerously high.     

Effect of donors' intravenous drug use, cigarette smoking, and alcohol dependence on kidney transplant outcome

BACKGROUND: The shortage of organ donors for kidney transplants has made the expansion of the kidney donor pool a clinically significant issue. Previous studies suggest that kidneys from donors with a history of intravenous (IV) drug, cigarette, and/or alcohol use are considered to be a risky choice. However, these kidneys could potentially be used and expand the kidney supply pool if no evidence shows their association with adverse transplant outcomes. METHODS: This study analyzed the United Network for Organ Sharing dataset from 1994 to 1999 using Kaplan-Meier survival analysis and Cox modeling. The effects on transplant outcome (graft and recipient survival) were examined with respect to the donors' IV drug use, cigarette smoking, and alcohol dependency. Covariates including the recipient variables, the donor variables, and the transplant procedure variables were included in the Cox models. RESULTS: The results show that the donors' history of cigarette smoking is a statistically significant risk factor for both graft survival (hazard ratio=1.05, P<0.05) and recipient survival (1.06, P<0.05), whereas neither IV drug use nor alcohol dependency had significant adverse impact on graft or recipient survival. CONCLUSIONS: Assuming that adequate testing for potential infections is performed, there is no evidence to support avoiding the kidneys from donors with IV drug use or alcohol dependency in transplantation. Utilizing these kidneys would clearly expand the potential pool of donor organs.     

Does periodontal treatment improve glycemic control in diabetic patients? A meta-analysis of intervention studies

Previous analyses regarding effects of periodontal treatment on glycemic control included studies where causal association might not be assumed, or the results were reported non-quantitatively. We initiated this meta-analysis of 10 intervention studies to quantify the effects of periodontal treatment on HbA1c level among diabetic patients, to explore possible causes for the discrepant reports, and to make recommendations for future studies. Data sources were MEDLINE (January, 1980, to January, 2005), the EBMR, Cochrane Register, and bibliographies of the published articles. Three investigators extracted data regarding intervention, outcomes, and effect size. A total of 456 patients was included in this analysis, with periodontal treatment as predictor and the actual change in hemoglobin A1c level as the outcome. The weighted average decrease in actual HbA1c level was 0.38% for all studies, 0.66% when restricted to type 2 diabetic patients, and 0.71% if antibiotics were given to them. However, none was statistically significant.     

Leukocyte populations and steroid receptor expression in human first-trimester decidua; regulation by antiprogestin and prostaglandin E analog

CONTEXT: Progesterone acting via its cognate receptor is critical to maintaining a viable endometrial environment for implantation and pregnancy. During medical termination of pregnancy, the biological effect of progesterone is pharmacologically withdrawn and prostaglandins administered exogenously. Leukocytes within the uterus are the effector cells of an inflammatory response and play important roles in both tissue breakdown and remodeling. OBJECTIVE: The aim of this study was to identify the separate and combined effects of the antiprogestin Mifepristone (single dose, 200 mg) and the prostaglandin E (PGE) analog (gemeprost) on leukocyte populations and steroid receptor expression in human first-trimester decidua. PATIENTS: Eighty women were recruited from the termination of pregnancy service with a gestational age of between 35 and 65 d at the time of surgical termination of pregnancy. MAIN OUTCOME MEASURES: Immunohistochemistry was used to measure macrophage (CD68 +ve), neutrophil (neutrophil elastase +ve), and uterine natural killer cell (CD56 +ve) populations and progesterone (PR(A) and PR(B)), estrogen (ERalpha and ERbeta), and androgen receptor (AR) expression. RESULTS: After administration of both antiprogestin and the PGE analog, macrophage and neutrophil numbers were significantly increased, whereas natural killer cell numbers were unchanged. Antiprogestin and PGE analog coadministration also significantly decreased PR and ERalpha immunoreactivity but had no effect on androgen receptor or ERbeta receptor expression. PGE analog alone was also capable of reducing PR expression. CONCLUSIONS: In this study, we demonstrate that the inflammatory response induced by antiprogestin in combination with PGE analog is accompanied by both increases in macrophages and neutrophils numbers and decreases in PR and ERalpha expression in human first-trimester decidua.     

Effects of the (-)-anti-11R,12S-dihydrodiol 13S,14R-epoxide of dibenzo

The tumor suppressor protein p53 plays an important role in recognition of DNA damage and induction of subsequent cell cycle arrest. One of its target genes encodes the protein p21(WAF1), which is involved in mediation of growth arrest after DNA damage has occurred. Dibenzo[a,l]pyrene (DB[a,l]P) is a polycyclic aromatic hydrocarbon which is an exceptionally potent carcinogen. A reactive secondary metabolite of DB[a,l]P, the fjord region (-)-anti-11R,12S-dihydrodiol 13R,14S-epoxide [(-)-anti-DB[a,l]PDE] was used to investigate DNA damage via adduct formation and cell cycle arrest in human diploid fibroblast cell cultures (HDF). Synchronous HDF were exposed to increasing concentrations (0.014, 0.028 and 0.07 microM) of (-)-anti-DB[a,l]PDE and at 1, 12, 24 and 42 h after treatment cell pellets were analyzed for DNA adduct formation and cell cycle arrest. Exposure of HDF to 0.07 microM (-)-anti-DB[a,l]PDE caused a total DNA binding level of 113 pmol adducts/mg DNA (42 h after treatment). G(1) arrest was induced by this treatment, with 91% of the cells remaining in G(1) phase compared with the solvent-treated control cultures (50%) as analyzed by propidium iodide staining and flow cytometry. Further investigation of the percentage of cells in S phase by 5-bromo-2'-deoxyuridine incorporation confirmed the G(1) arrest in HDF treated with 0.07 microM (-)-anti-DB[a,l]PDE, with only 1.5% of the cells moving into S phase compared with 39% in the control 42 h after treatment. Induction of p53 and p21(WAF1) was demonstrated by western blot analysis.