Defecating proctography: A pictorial essay.

OBJECTIVES: To provide an illustrative description of the technique and spectrum of findings in defecating proctography. KEY FINDINGS: Important findings on defecating proctography include rectocoele, enterocoele, sigmoidocoele, cystocoele, intussusception, rectal prolapse, descending perineum, incomplete emptying, anismus, and faecal incontinence. This review article illustrates these key findings with examples. CONCLUSION: Defecating proctography is a well-established and cost-effective method of assessing disordered defecation. In conjunction with clinical information and other diagnostic tests, findings on defecating proctography can guide appropriate multidisciplinary management and may lead to improvement in embarrassing and debilitating symptoms in many patients. IMPLICATIONS FOR PRACTICE: This review article provides a suggested technique and covers the spectrum of findings on defecating proctography.

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

The expanded criteria donor policy: an evaluation of program objectives and indirect ramifications.

The expanded criteria donor (ECD) policy was formalized in 2002, which defined higher-risk deceased donor kidneys recovered for transplantation. There has not been a comprehensive examination of the impact of policy on the allocation of ECD kidneys, waiting times for transplant, center listing patterns or human leukocyte antigen (HLA) matching. We examined transplant candidates from 1998 to 2004 utilizing a national database. We constructed models to assess alterations in recipient characteristics of ECD kidneys and trends in waiting time and cold ischemia time (CIT) associated with policy. We also evaluated the impact of the proportion of center candidate listings for ECD kidneys on waiting times. Elderly recipients were more likely to receive ECDs following policy (odds ratio = 1.36, p < 0.01). There was no association of decreased CIT or pretransplant dialysis time while increasing HLA mismatching with policy inception. Over one quarter of centers listed < 20% of candidates for ECDs, while an additional quarter of centers listed > 90%. Only centers with selective listing for ECDs offered reduced waiting times to ECD recipients. The ECD policy demonstrates potential to achieve certain ascribed goals; however, the full impact of the program, reaching all transplant candidates, may only be achieved once ECD listing patterns are recommended and adopted accordingly.

Fourier transform infrared studies on deblocking and crosslinking mechanisms of some fluorine containing monocomponent polyurethanes.

The thermal reactivity of a set of different blocked perfluoropolyether (PFPE) containing polyisocyanates and one monocomponent polyurethane containing a PFPE diol was investigated by Fourier transform infrared (FT-IR) spectroscopy. With the former series of products the deblocking kinetics at 90 degrees C and 120 degrees C were investigated with time-dependent spectral data, showing the highest thermal deblocking activity for 3,5 dimethylpyrazole blocking agent. The crosslinking reaction of the PFPE diol with ketoxime blocked isocyanurate at 150 degrees C was monitored by infrared (IR) spectroscopy and two-dimensional (2D) correlation analysis; the results suggested a prevailing direct condensation mechanism and the formation of urea byproducts in the later stages of reaction. Both synchronous and asynchronous spectra were considered and discussed, pointing out the time relation of the chemical functions during the crosslinking experiment.

The role of CBP in estrogen receptor cross-talk with nuclear factor-kappaB in HepG2 cells.

Functional interactions or cross-talk between ligand-activated nuclear receptors and the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) may play a major role in ligand-mediated modification of diseases processes. In particular, the cardioprotective effects of estrogen replacement therapy are thought to be due in part to the ability of ligand-bound estrogen receptor (ER) to inhibit NF-kappaB function. In the current study 17beta-estradiol-bound ERalpha interfered with cytokine-induced activation of a NF-kappaB reporter in HepG2 cells. The estrogen metabolite, 17alpha-ethinyl estradiol, and the phytoestrogen, genistein, were also effective inhibitors of NF-kappaB activation, whereas tamoxifen, 4-hydroxytamoxifen, and raloxifene were inactive. This inhibition was reciprocal, as NF-kappaB interfered with the trans-activation properties of ERalpha. Ligand-bound ERalpha did not inhibit NF-kappaB binding to DNA, but it did decrease the histone acetyltransferase activity required for NF-kappaB transcriptional activity. Coexpression of the transcription coactivator CREB binding protein (CBP), but not steroid receptor coactivator 1a, reversed the ERalpha-mediated inhibition of NF-kappaB activity. Mammalian two-hybrid experiments also revealed that ligand-bound ERalpha can interact functionally with CBP-NF-kappaB complexes. We suggest that CBP targeting by ERalpha results in the inhibition of NF-kappaB and may occur through formation of transcriptionally inert multimeric complexes that are dependent upon the nature of the ERalpha ligand.

The activation of plasminogen activator inhibitor-1 expression by IL-1beta is attenuated by estrogen in hepatoblastoma HepG2 cells expressing estrogen receptor alpha.

A low estrogen status in postmenopausal women is associated with elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1). In this study, the ability of estrogen compounds to regulate PAI-1 expression was determined in a hepatocyte HepG2 cell line made to stably express estrogen receptor alpha (ERalpha). In both the wild type and ER expressing HepG2 cells, estrogen had no effect on basal PAI-1 expression. However, in the ER expressing cells the ability of IL-1beta to increase PAI-1 mRNA and protein levels was attenuated by 17beta-estradiol, tamoxifen and twelve estrogen components of Premarin. In contrast, the mixed agonist/antagonist raloxifene had weak agonist activity and like the pure antagonist ICI 182780, it dose dependently blocked the effect of 17beta-estradiol on IL-1beta stimulated PAI-1 levels. These results suggest that estrogen agonists may lower PAI-1 levels in vivo by inhibiting cytokine activated PAI-1 expression by an ER dependent mechanism.

Estrogen regulation of the apolipoprotein AI gene promoter through transcription cofactor sharing.

Estrogen replacement therapy increases plasma concentrations of high density lipoprotein and its major protein constituent, apolipoprotein AI (apoAI). Studies with animal model systems, however, suggest opposite effects. In HepG2 cells stably expressing estrogen receptor alpha (ERalpha), 17beta-estradiol (E2) potently inhibited apoAI mRNA steady state levels. ApoAI promoter deletion mapping experiments indicated that ERalpha plus E2 inhibited apoAI activity through the liver-specific enhancer. Although the ERalpha DNA binding domain was essential but not sufficient for apoAI enhancer inhibition, ERalpha binding to the apoAI enhancer could not be detected by electrophoretic mobility shift assays. Western blotting and cotransfection assays showed that ERalpha plus E2 did not influence the abundance or the activity of the hepatocyte-enriched factors HNF-3beta and HNF-4, two transcription factors essential for apoAI enhancer function. Expression of the ERalpha coactivator RIP140 dramatically repressed apoAI enhancer function in cotransfection experiments, suggesting that RIP140 may also function as a coactivator on the apoAI enhancer. Moreover, estrogen regulation of apoAI enhancer activity was dependent upon the balance between ERalpha and RIP140 levels. At low ratios of RIP140 to ERalpha, E2 repressed apoAI enhancer activity, whereas at high ratios this repression was reversed. Regulation of the apoAI gene by estrogen may thus vary in direction and magnitude depending not only on the presence of ERalpha and E2 but also upon the intracellular balance of ERalpha and coactivators utilized by ERalpha and the apoAI enhancer.

Regulation of human estrogen receptor by phytoestrogens in yeast and human cells.

Phytoestrogens are defined as plant substances that are structurally or functionally similar to estrogen. They are present in many foods and their higher consumption in certain populations has been correlated with protection against many diseases including coronary heart disease, breast cancer and endometrial and ovarian cancer. In this report, ten phytoestrogens with diverse chemical structures were studied for their binding to the human estrogen receptor and their transcription activation properties in yeast and mammalian cells. Our results showed that some of these compounds bind with relatively high affinity to the estrogen receptor and activate the receptor in the yeast and mammalian cell system. In addition, none of these compounds showed anti-estrogenic activity. We conclude that the yeast system accurately predicts the estrogenic activity of compounds with diverse chemical structures in mammalian cells. In addition, our data with phytoestrogens that do not show transcription activation properties raise the possibility that these compounds may exert their biological effects through pathways different from the classical estrogen signalling mechanism.

Molecular detection of primary bladder cancer by microsatellite analysis.

Microsatellite DNA markers have been widely used as a tool for the detection of loss of heterozygosity and genomic instability in primary tumors. In a blinded study, urine samples from 25 patients with suspicious bladder lesions that had been identified cystoscopically were analyzed by this molecular method and by conventional cytology. Microsatellite changes matching those in the tumor were detected in the urine sediment of 19 of the 20 patients (95 percent) who were diagnosed with bladder cancer, whereas urine cytology detected cancer cells in 9 of 18 (50 percent) of the samples. These results suggest that microsatellite analysis, which in principle can be performed at about one-third the cost of cytology, may be a useful addition to current screening methods for detecting bladder cancer.