Low-dose mifepristone inhibits endometrial proliferation and up-regulates androgen receptor

Mifepristone in daily low doses has contraceptive potential by inhibiting ovulation. Follicular development is maintained, and although the endometrium is exposed to unopposed estrogen, there are no signs of hyperplasia or atypia. The mechanism of this antiestrogenic action is unknown. We have investigated the effect of daily low-dose mifepristone on proliferation markers and steroid receptors in surface epithelium, glands, and stroma of the endometrium. Endometrial biopsies were collected from 16 women before (late proliferative) and 60 and 120 d after taking 2 or 5 mg mifepristone daily for 120 d. Endometrial proliferation (H3 mitosis marker) and steroid (estrogen, progesterone, and androgen) receptor content were studied using standard immunocyotchemistry techniques. There was a significant decrease in the expression of H3 mitosis marker (P 相似文献   

Effects of cypermethrin on marine plankton communities: a simulated field study using mesocosms

In earlier single-species toxicity tests we showed the negative effects on the calanoid copepod Acartia tonsa upon exposure to cypermethrin, a pesticide used in treatment for sea lice in salmon farming. In the present study we assessed effects at a higher level of biological organization and under a more realistic exposure scenario using mesocosms. The results showed that simulated field studies (SFSs) could be conducted with the mesocosms designed here. When cypermethrin was applied inside these mesocosms, its concentration decreased exponentially following a first-order kinetics model. The pesticide immediately reduced zooplankton density and biodiversity not only directly, by killing copepods, but also indirectly, by increasing the numbers of rotifers. Zooplankton density recovered after treatment, but zooplankton biodiversity remained altered. In an open environment, however, the rapid dissipation of the pesticide, coupled with population processes of compensation, migration, and immigration, may lead to recovery of the affected zooplankton communities.     

Comparison of MRI and CT for detection of acute intracerebral hemorrhage

Context  Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. Objective  To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. Design, Setting, and Patients  A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. Main Outcome Measures  Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. Results  The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT—each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. Conclusion  MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.      

Cholestatic pruritus - the role of cutaneous mast cells and nerves

BACKGROUND: The pathogenesis of pruritus in cholestatic liver disease is poorly understood. Cutaneous mast cells and nerves are thought to contribute to pruritus in several dermatological diseases. AIM: To determine if cutaneous mast cell density, neural density and mast cell-neural interaction are increased in patients with pruritus and cholestatic liver disease. METHODS: Skin biopsy specimens from (i). patients with pruritus due to cholestatic liver disease (CLDP+; n = 6), (ii). patients with chronic liver disease without pruritus (CLDP-; n = 5), and (iii). healthy controls (n = 6) were studied. Biopsies were dual stained immunohistochemically for mast cells and nerves. RESULTS: Mast cell density in the control group was not significantly different from that in CLDP+ group or from that in the CLDP- group. Similarly neural density was not significantly different between groups when assessed either in terms of total nerve area, or in terms of the number of neural elements seen. The frequency of mast cell-nerve contact was not significantly different between groups. CONCLUSIONS: These findings suggest that mast cells, nerves or interaction between the two may not contribute to cholestatic pruritus. Therefore, therapies targeted at cutaneous mast cells or nerves are unlikely to be of benefit.     

An integrated system for planning, navigation and robotic assistance for skull base surgery

BACKGROUND：We developed an image-guided robot system to provide mechanical assistance for skull base drilling, which is performed to gain access for some neurosurgical interventions, such as tumour resection. The motivation for introducing this robot was to improve safety by preventing the surgeon from accidentally damaging critical neurovascular structures during the drilling procedure. METHODS： We integrated a Steahhstation（（R）） navigation system, a NeuroMate（（R）） robotic arm with a six-degree-of-freedom force sensor, and the 3D Slicer visualization software to allow the robotic arm to be used in a navigated,cooperatively-controlled fashion by the surgeon. We employed virtual fixtures to constrain the motion of the robot-held cutting tool, so that it remained in the safe zone that was defined on a preoperative CT scan. RESULTS： We performed experiments on both foam skull and cadaver heads.     

Development of double blind gluten and casein free test foods for use in an autism dietary trial

Background: Autism is a severe long‐term neurodevelopmental disorder. Families are increasingly undertaking a gluten and casein free (GFCF) diet in response to largely anecdotal reports of autistic clinical improvement. Exclusion of staple foods can place these children, with self‐imposed limited diets, at nutritional risk (Keen, 2007). There is an urgent need to investigate the efficacy of GFCF diets in an adequately powered, medium term, randomised controlled trial (Millward et al., 2007). However, double blinding to the removal of gluten and/or casein is desirable but complex to accomplish. Therefore, this study was essential preparation for a large scale study and investigated the feasibility of producing test foods to achieve double‐blinding which are transportable, easy to prepare, palatable and suitable for daily consumption by young children with autism. Methods: Heron Foods Cork, developed a range of test foods including a muffin, porridge and batter mix, lemon and almond cookies and chocolate krispie bars. The estimated average habitual intake (Gregory et al., 1995) of gluten (10 g) and/or casein (10 g) was added as outlined below: Test Food with gluten and casein added; Test Food with added casein only; Test Food with added gluten only; Test Food with no gluten or casein added. Groups were randomly labelled A–D. The foods’ GFCF status or presence of additions was confirmed by independent assay. R&D and ethical approval was given for health professionals to recruit 60 children with autism (3–6 years) in Newcastle, Edinburgh and London and to randomly allocate to the above groups. Following assessment of eligibility and informed consent, families received a supply of test foods, detailed cooking instructions and behaviour and food preference questionnaires for self‐completion. Parents offered test foods for 28 days and recorded daily consumption. As this study investigated the acceptability of the test foods and not the effect of GFCF diet on autism, gluten and casein containing foods were not withdrawn from the child's diet. Telephone dietetic support was available throughout. Outcomes were measured by food consumption diaries, a test foods acceptability questionnaire and telephone interviews with a sub‐set of parents. Parents and all researchers were blind to group allocation. Results: A total of 52 children were recruited with only three families withdrawing during the 28 days due to food refusal. Results are available for the first 43 children [A – 9, B – 10, C – 13, D – 11]. Of 38 parents responding 63% stated that their children were ‘usually willing to try new foods’ [A – 86%, B – 67%, C – 42%, D – 70%]. Ninety‐five percent of the children (n = 40) [A – 89%, B – 90%, C – 100%, D – 100%] tried at least some foods over the 28 days. Muffins and chocolate krispies were most readily accepted. Porridge and batter mix were least well liked. Children in groups A and D were most likely to consume more of the foods offered. The status of the groups is not yet known but these results suggest that porridge could be removed as an option. At interview parents confirmed these findings and suggested an alternative savoury food item such as bread should be available. Discussion: Families demonstrated a high level of motivation and commitment to this study indicating their desire for dietary research in autism. The research team encountering considerable challenges in both the planning and execution of this study, but despite this, a range of test foods have been produced suitable for young children with autism. Conclusion: This is the first study to develop and test a range of double‐blind test foods for regular consumption by young children with autism. This is essential preparation for a large scale multicentered RCT of gluten and casein free diets in the management of autism. Funded by Research Autism & The Children's Foundation. This work was supported by the BDA General Education Trust. References Gregory, J.R., Collins, D.L., Davies, P.S.W., Hughes, J.M. & Clarke, P.C. (1995) National Diet and Nutrition Survey: children aged 1 1/2 to 4 1/2 years, volume 1: Report of the Diet and Nutrition. London: HMSO. Keen, D.V. (2007) Childhood autism, feeding problems and failure to thrive in early infancy. Seven case studies. Eur. Child. Adolesc. Psychiatry. Published online Sept 14th 2007. Millward, C., Ferriter, M., Calver, S., & Connell‐Jones, G. (2007) Gluten‐ and casein‐free diets for autistic spectrum disorder. Cochrane Database Syst. Rev. 4, CD003498.     

Enhanced Prospects for Drug Delivery and Brain Targeting by the Choroid Plexus–CSF Route

The choroid plexus (CP), i.e., the blood–cerebrospinal fluid barrier (BCSFB) interface, is an epithelial boundary exploitable for drug delivery to brain. Agents transported from blood to lateral ventricles are convected by CSF volume transmission (bulk flow) to many periventricular targets. These include the caudate, hippocampus, specialized circumventricular organs, hypothalamus, and the downstream pia–glia and arachnoid membranes. The CSF circulatory system normally provides micronutrients, neurotrophins, hormones, neuropeptides, and growth factors extensively to neuronal networks. Therefore, drugs directed to CSF can modulate a variety of endocrine, immunologic, and behavioral phenomema; and can help to restore brain interstitial and cellular homeostasis disrupted by disease and trauma. This review integrates information from animal models that demonstrates marked physiologic effects of substances introduced into the ventricular system. It also recapitulates how pharmacologic agents administered into the CSF system prevent disease or enhance the brain’s ability to recover from chemical and physical insults. In regard to drug distribution in the CNS, the BCSFB interaction with the blood–brain barrier is discussed. With a view toward translational CSF pharmacotherapy, there are several promising innovations in progress: bone marrow cell infusions, CP encapsulation and transplants, neural stem cell augmentation, phage display of peptide ligands for CP epithelium, CSF gene transfer, regulation of leukocyte and cytokine trafficking at the BCSFB, and the purification of neurotoxic CSF in degenerative states. The progressively increasing pharmacological significance of the CP–CSF nexus is analyzed in light of treating AIDS, multiple sclerosis, stroke, hydrocephalus, and Alzheimer’s disease.