Role of Low Exposure to Metals as Male Reproductive Toxicants

The objective of the study was to examine the associations between environmentally relevant low metal concentrations and semen quality parameters in men. The concentrations of zinc (Zn), copper (Cu), cadmium (Cd), arsenic (As), selenium (Se), and lead (Pb) in the seminal plasma and urine were measured from 196 male human subjects in Taiwan. Urinary Cd concentrations were negatively associated with sperm viability (p=0.006). Seminal plasma Cu concentrations of the normal group (\u3e= 15 x 10(6)/ml) were significantly lower than those of the abnormal group (p=0.023). However, the linear regression analysis showed a weak association between Cu concentration and sperm concentration, along with other semen parameters. No significant relationship between other metals (As, Pb, Zn, and Se) and semen quality was observed

The role of insulin glulisine to improve glycemic control in children with diabetes mellitus

Glulisine (Apidra®) is a rapid-acting human insulin analog approved for use in children with diabetes mellitus ≥4 years of age. Management of children with type 1 diabetes has seen a shift in favor of mimicking normal physiological insulin responses with multiple daily injections or continuous subcutaneous insulin infusions (CSII). Few studies have compared the rapid-acting insulin analogs in this population but limited data indicate that glulisine is as effective as lispro when used in a basal–bolus regimen. This review appraises the current available studies and reviews on insulin glulisine in children. An extensive keyword search of ‘insulin glulisine’, ‘insulin analogs’, and ‘Apidra’ in the pediatric population was performed. These studies have suggested that glulisine is safe, well tolerated, and is an effective option in the diabetes armamentarium. Further studies are needed to determine its safety for use in CSII pumps in the pediatric population

Identity of blactx-m carrying plasmids in sequential esbl-e. Coli isolates from patients with recurrent urinary tract infections

Plasmid-mediated multidrug resistance in E. coli is becoming increasingly prevalent. Considering this global threat to human health, it is important to understand how plasmid-mediated resistance spreads. From a cohort of 123 patients with recurrent urinary tract infections (RUTI) due to extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL E. coli), only five events with a change of ESBL E. coli strain between RUTI episodes were identified. Their blaCTX-M encoding plasmids were compared within each pair of isolates using optical DNA mapping (ODM) and PCR-based replicon typing. Despite similar blaCTX-M genes and replicon types, ODM detected only one case with identical plasmids in the sequential ESBL E. coli strains, indicating that plasmid transfer could have occurred. For comparison, plasmids from seven patients with the same ESBL E. coli strain reoccurring in both episodes were analyzed. These plasmids (encoding blaCTX-M-3, blaCTX-M-14, and blaCTX-M-15 ) were unaltered for up to six months between recurrent infections. Thus, transmission of blaCTX-M plasmids appears to be a rare event during the course of RUTI. Despite the limited number (n = 23) of plasmids investigated, similar blaCTX-M-15 plasmids in unrelated isolates from different patients were detected, suggesting that some successful plasmids could be associated with specific strains, or are more easily transmitted

Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

<p>Abstract</p> <p>Background</p> <p>Glioblastoma multiforme (GBM) is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death.</p> <p>To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis.</p> <p>Results</p> <p>Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates <it>a priori </it>knowledge with expression data. Principal component analysis (PCA) revealed two discriminating patterns between migrating and stationary glioma cells: i) global down-regulation and ii) global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF). siRNA mediated knockdown yielded reduced <it>in vitro </it>migration and <it>ex vivo </it>invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells.</p> <p>Conclusion</p> <p>Gene expression profiling of migratory glioma cells induced to disperse <it>in vitro </it>affords discovery of genomic signatures; selected candidates were validated clinically at the transcriptional and translational levels as well as through functional assays thereby underscoring the fidelity of the discovery algorithm.</p

Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

BACKGROUND: Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. METHODS: A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. RESULTS: The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). CONCLUSION: This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

Constructions of expression vectors of polyhydroxybutyrate-co-hydroxyvalerate (PHBV) and transient expression of transgenes in immature oil palm embryos.

Polyhydroxybutyrate-co-hydroxyvalerate (PHBV) is a polyhydroxyalkanoate (PHA) bioplastic group with thermoplastic properties is thus high in quality and can be degradable. PHBV can be produced by bacteria, but the process is not economically competitive with polymers produced from petrochemicals. To overcome this problem, research on transgenic plants has been carried out as one of the solutions to produce PHBV in economically sound alternative manner. Four different genes encoded with the enzymes necessary to catalyze PHBV are bktB, phaB, phaC and tdcB. All the genes came with modified CaMV 35S promoters (except for the tdcB gene, which was promoted by the native CaMV 35S promoter), nos terminator sequences and plastid sequences in order to target the genes into the plastids. Subcloning resulted in the generation of two different orientations of the tdcB, pLMIN (left) and pRMIN (right), both 17.557 and 19.967 kb in sizes. Both plasmids were transformed in immature embryos (IE) of oil palm via Agrobacterium tumefaciens. Assays of GUS were performed on one-week-old calli and 90% of the calli turned completely blue. This preliminary test showed positive results of integration. Six-months-old calli were harvested and RNA of the calli were isolated. RT-PCR was used to confirm the transient expression of PHBV transgenes in the calli. The bands were 258, 260, 315 and 200 bp in size for bktB, phaB, phaC and tdcB transgenes respectively. The data obtained showed that the bktB, phaB, phaC and tdcB genes were successfully integrated and expressed in the oil palm genome

The rising tide of obesity and diabetes: An evaluation of obesity and diabetes in pregnancy

The prevalence of pregnant women with obesity and gestational diabetes (GDM) is rising. It is known that pregnant women with obesity and women with GDM have an increased risk of neonatal morbidity. This thesis describes the maternal characteristics of a sample of women in the Sydney Western region of New South Wales. The central aim of our study was to evaluate the association between obesity and gestational diabetes with maternal and neonatal outcomes in this cohort of women. Our initial study evaluated the association between obesity with maternal and neonatal outcomes over a four year time period. Obese women comprised 22% of the included 38917 women. Obese women had a higher likelihood of macrosomia (3.6%), p=0.001 and perinatal death (0.9%), p<0.05. Our second study evaluated gestational weight gain in women with gestational diabetes. A greater proportion of women that were either in the obese or overweight group (66%) gained weight above IOM guidelines at 36 weeks compared with normal pre-gravid BMI women (33%), p<0.001. Our third study evaluated the profile of a group of 30 women with GDM, and the effect of diet and physical activity advice during their pregnancy. There was a modest improvement in dietary behavior following dietetic/medical advice. Our study has demonstrated the adverse outcomes associated with obesity in pregnancy and in the group of women with GDM and/or obesity

The rising tide of obesity and diabetes: An evaluation of obesity and diabetes in pregnancy

The prevalence of pregnant women with obesity and gestational diabetes (GDM) is rising. It is known that pregnant women with obesity and women with GDM have an increased risk of neonatal morbidity. This thesis describes the maternal characteristics of a sample of women in the Sydney Western region of New South Wales. The central aim of our study was to evaluate the association between obesity and gestational diabetes with maternal and neonatal outcomes in this cohort of women. Our initial study evaluated the association between obesity with maternal and neonatal outcomes over a four year time period. Obese women comprised 22% of the included 38917 women. Obese women had a higher likelihood of macrosomia (3.6%), p=0.001 and perinatal death (0.9%), p<0.05. Our second study evaluated gestational weight gain in women with gestational diabetes. A greater proportion of women that were either in the obese or overweight group (66%) gained weight above IOM guidelines at 36 weeks compared with normal pre-gravid BMI women (33%), p<0.001. Our third study evaluated the profile of a group of 30 women with GDM, and the effect of diet and physical activity advice during their pregnancy. There was a modest improvement in dietary behavior following dietetic/medical advice. Our study has demonstrated the adverse outcomes associated with obesity in pregnancy and in the group of women with GDM and/or obesity

Divide and conquer : the multidisciplinary approach to achieving significant long-term weight loss and improved glycemic control in obese patients with type 2 diabetes

Type 2 diabetes has become a worldwide epidemic, esti¬mated to affect 1 in 14 adults, or 380 million people, globally by 2025.The problem is particularly acute in Australia, where the preva¬lence of diagnosed diabetes more than doubled between 1989 and 2005, amounting to 3 million people affected by the disease. Diabetes is the most common reason for renal dialysis, blindness in people < 60 years of age, nontraumatic lower-limb amputation, and cardiovascular dis¬ease and is the sixth-highest cause of death by disease in Australia