SNP discovery, expression and cis-regulatory variation in the UGT2B genes.

UGT2B enzymes metabolize multiple endogenous and exogenous molecules, including steroid hormones and clinical drugs. However, little is known about the inter-individual variation in gene expression and its determinants. We re-sequenced candidate regulatory regions and the partial coding regions (41.1 kb) of UGT2B genes and identified 332 genetic variants. We measured gene expression in normal breast and liver samples and observed different patterns. The expression levels varied greatly across individuals in both tissues and were significantly correlated with each other in liver. Genotyping of tagging single-nucleotide polymorphisms (SNPs) in the same samples and association tests between genotype and transcript levels identified 62 variants that were associated with at least one UGT2B mRNA levels in either tissue. Most of these cis-regulatory SNPs were not shared between tissues, suggesting that this gene family is regulated in a tissue-specific manner. Our results provide insight into studying the role of UGT2B variation in hormone-dependent cancers and drug response.

Chemoattractant agents and nerve growth factor stimulate human spermatozoal reactive oxygen species generation.

OBJECTIVE: To investigate the ability of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), complement 5a (C5a), and nerve growth factor (NGF) to stimulate human spermatozoal reactive oxygen species generation in fertile and infertile patients. DESIGN: Prospective, controlled study measuring human spermatozoal reactive oxygen species generation after addition of f-MLP, C5a, or NGF. SETTING: A large health maintenance organization. PATIENTS, PARTICIPANTS: The fertile group consisted of 14 men with established fertility and normal bulk semen parameters. The infertile group was comprised of 8 men who were infertile after > 18 months of unprotected sexual intercourse. INTERVENTIONS: The sperm samples were subjected to four test conditions: f-MLP stimulation, C5a stimulation, NGF stimulation, and no stimulation (control). MAIN OUTCOME MEASURE: Reactive oxygen generation was measured over a 15-minute period using the method of chemiluminescence. RESULTS: In both the fertile and infertile groups, reactive oxygen species generation was significantly enhanced by f-MLP, C5a, and NGF compared with controls. No significant difference in f-MLP- and C5a-stimulated reactive oxygen production was demonstrated between the infertile and fertile groups; however, there was a significant difference in reactive oxygen generation between infertile and fertile subjects when stimulated with NGF. CONCLUSIONS: The current study represents the first report of f-MLP-, C5a-, and NGF-stimulated reactive oxygen species generation by human spermatozoa. Nerve growth factor enhanced reactive oxygen species production to a greater extent in infertile subjects compared with fertile subjects. This points to a possible NGF-mediated biochemical defect in the sperm of infertile patients.

Neuroprotective action and free radical scavenging activity of Guttiferone-A, a naturally occurring prenylated benzophenone.

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 µM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage.

Transvaginal repair of bladder injury during vaginal hysterectomy.

We report on the transvaginal repair of iatrogenic bladder perforations that occurred during vaginal hysterectomy. Systematic evaluation of the bladder injury, adequate vaginal exposure and meticulous bladder closure resulted in a successful outcome in 3 recent cases.

Nonsurgical management of threatened upper urinary tracts and incontinence in children with myelomeningocele.

The 2 major urological objectives in treating the child with myelomeningocele are to preserve renal function and achieve continence. We report our success in managing these cases with nonsurgical therapy. From 1981 to 1991, 45 patients with myelomeningocele 1 to 15 years old were evaluated urodynamically before and after initiating nonsurgical treatment. Pretreatment urodynamics identified 2 groups. Group 1 consisted of 31 patients with leak point pressure of 40 cm. water or more of whom 10 had grades II to V/V vesicoureteral reflux and 4 had moderate or severe hydronephrosis. Group 2 consisted of 14 incontinent patients with leak point pressure of less than 40 cm. water and no reflux or hydronephrosis. Both groups were treated with intermittent catheterization, anticholinergic medications and fluid restriction. Within a mean followup of 5.5 years nonsurgical intervention resulted in lowering maximum detrusor pressure at maximum cystometric capacity to less than 40 cm. water in 22 of 31 group 1 patients (71%), and in resolving vesicoureteral reflux in 7 of 10 (70%) and hydronephrosis in 3 of 4 (75%) group 1 patients. Of 4 patients in group 1 with persistent high grade vesicoureteral reflux or severe hydronephrosis 3 (10%) required augmentation cystoplasty. With nonsurgical management 18 patients (40%) were completely continent, 18 (40%) required 2 or less pads daily and 9 (20%) required more than 2 pads daily. Nonsurgical management alone was effective in preserving the upper urinary tract in 90% of patients and it provided satisfactory continence in 80%. Surgical management should be reserved for the minority of patients whose upper tract changes do not resolve and for those whose degree of continence is not satisfactory with nonsurgical management.

Fracturas del cuello femoral no diagnosticadas en casos ipsilaterales con la diáfisis / Femoral neck fractures with ipsilateral diaphyseal fractures

Estudio observacional tipo serie de casos, durante el periodo enero de 1990 hasta diciembre de 1999, de pacientes atendidos en el Hospital Universitario del Valle y que consultaron al servicio de urgencias de dicha institución. Se tomaron del universo de pacientes atendidos con fracturas de la diafisis femoral, aquellos con fracturas ipsilaterales del cuello del femur y se estudiaron las que no fueron detectadas en el preoperatorio. En este periodo se trataron 1954 fracturas de la diafisis femoral, encontrando 73 casos con fracturas ipsilaterales del cuello del femur; de estas, 19 casos (26 por ciento) no fueron diagnosticadas al ingreso. De estas, 5 (7 por ciento) fueron detectadas en el intraoperatorio y las 14 restantes (19 por ciento) mediante los controles radiograficos postoperatorios inmediatos o tardios. Pretendemos llamar la atención sobre este tipo de fracturas, sobre la importancia de sospechar esta fractura concomitante con las fracturas de diafisis femoral en casos de riesgo, el mostrar el tipo de fracturas encontradas por nosotros y las alternativas de tratamiento empleadas; ademas, plantear la posibilidad de iatrogenia intraoperatoria por técnica quirurgica inadecuada o empeoramiento de lesiones mas benignas preoperatorias y no detectadas