Risperidone effects on heterochromatin: the role of kinase signaling.

Epigenetic effects of anti-psychotic medications are poorly understood. We have appropriated a model whereby heterochromatin is established through 24- or 48-h lipopolysaccharide (LPS) treatment, and tested the epigenetic effects of risperidone along the adenylyl cyclase/protein kinase A (AC/PKA) pathway in human liposarcoma cells that express the LPS-sensitive Toll-like receptor (TLR)-4. Human SW872 cells were cultured with LPS and mRNA expression levels and epigenetic modifications of dimethylated lysine 9 of histone 2 (H3K9me2), geterochromatin protein 1γ (HP1γ) and phospho-H3S10 at promoters of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL1ß were measured. Pharmacological manipulation of the AC/PKA pathway was achieved through treatment with a PKA inhibitor (H89), mitogen- and stress-activated kinase 1 (MSK1) inhibitor (SB-747651A) or forskolin. Twenty-four and 48-h LPS treatment establishes heterochromatin at selected promoters, corresponding to decreased mRNA expression. Concurrent risperidone treatment with LPS treatment can both 'block' and 'reverse' heterochromatin formation. Forskolin treatment resulted in a similar disassembling effect on heterochromatin. Conversely, inhibition of PKA by H89 or MSK1 both blocked 'normalizing' effects of risperidone on LPS-induced heterochromatin. Our results demonstrate that risperidone can disassemble heterochromatin, exerting this effect along the G-protein/AC/PKA pathway. This approach can also be utilized to investigate functional outcomes of single or combined pharmacological treatments on chromatin assemblies in human cells.

Efficacy and safety of transvaginal mesh kits in the treatment of prolapse of the vaginal apex: a systematic review.

BACKGROUND: Vaginal mesh kits are being used to surgically treat apical vaginal prolapse; however, their safety and efficacy are currently unknown. OBJECTIVES: To summarise success and complication rates for commonly used vaginal mesh kits in the treatment of apical prolapse. SEARCH STRATEGY: MEDLINE and other scientific databases were queried for primary research addressing the use of vaginal mesh kits for apical prolapse published between 1950 and 2007, including abstracts presented in major scientific meetings. SELECTION CRITERIA: Studies describing the use of mesh to support either the anterior or posterior compartment alone, for incontinence or fistula repair or not addressing the vaginal apex were excluded. DATA COLLECTION AND ANALYSIS: Identified studies were grouped by the mesh kit and complications categorised using the Dindo classification system. Weighted averages and confidence intervals were calculated on objective success, follow-up length and complications. MAIN RESULTS: Thirty studies totalling 2653 women met inclusion criteria. Objective success rates (95% CI) were Apogee (American Medical Systems Inc., Minnetonka, MN, USA) 95% (95-96), Prolift (Ethicon Women's Health and Urology, Somerville, NJ, USA) 87% (86-87) and posterior intravaginal slingplasty 88% (87-89). Reoperations not requiring anaesthesia (Dindo IIIa) occurred in 0.4-2.3% and requiring anaesthesia (Dindo IIIb) in 1.5-6.0%, with a follow up between 26 and 78 weeks. Mesh erosion was the most commonly reported complication occurring in 4.6-10.7%. AUTHOR'S CONCLUSIONS: Overall objective success using transvaginal mesh kits in restoring apical vaginal prolapse is high. However, an increasing number of women require surgical intervention for mesh-related complications based on limited data quality and short follow up. Further research addressing functional outcomes and the impact of these procedures on women's symptoms and quality of life is mandatory.

Vaginal evisceration long after vaginal hysterectomy.

BACKGROUND: Vaginal evisceration can take place many years after vaginal surgery. CASE: An 87-year-old woman presented with evisceration of small bowel through the vagina, 15 years after she underwent a vaginal hysterectomy. On physical examination, her vital signs were normal. Forty centimeters of small bowel was visible emerging from the vagina, appearing viable and nonedematous. Because of the high surgical risk, the bowel was replaced and the defect in the vaginal wall was repaired transvaginally. CONCLUSION: Vaginal evisceration can be treated by a transvaginal surgical approach. Factors such as the medical condition of the patient and the viability of the herniated viscus should dictate the optimal approach in each case.

The influence of maternal exercise on placental blood flow measured by Simultaneous Multigate Spectral Doppler Imaging (SM-SDI)

OBJECTIVE: To evaluate the effect of maternal isometric exercise on the placental blood flow as reflected by the velocimetric indices PI and RI derived from placental arteries. SUBJECTS: Thirty-four healthy women with normal singleton pregnancies between 22 and 35 weeks of gestation. METHODS: All subjects underwent an isometric handgrip exercise test. Maternal blood pressure and heart rate together with placental PI and RI were measured at rest, during the exercise and in the post-exercise recovery phase. All Doppler measurements were obtained using the Simultaneous Multigate Spectral Doppler Imaging (SM-SDI) technique, a new ultrasound modality that enables a Doppler study of multiple locations to take place within a very short time. RESULTS: There was a significant increase in the mean values of the maternal blood pressure and heart rate during the exercise and a significant decline in the recovery phase. There was no significant change in the mean values of the Doppler indices throughout the examination. CONCLUSION: Isometric handgrip exercise test during pregnancy does not affect the impedance of the placental circulation.