新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Stimulatory effect of counterflow centrifugal elutriation in large-scale separation of peripheral blood monocytes can be reversed by storing the cells at 37 degrees C.

Transfusion of peripheral blood monocytes may be of benefit as adjuvant treatment of leukopenic patients with serious infections. To study the feasibility of this approach, a large-scale monocyte separation procedure employing leukapheresis, density gradient centrifugation, and counterflow centrifugal elutriation was established. By processing 5 to 6 liters of normal donor blood, it was possible to obtain a mean of 1.1 x 10(9) (range: 0.5-1.7 x 10(9) cells) of mononuclear cells, of which 89% (range: 82-94%) were monocytes by Wright's stain morphology. When the elutriation was performed in XVIVO-10, a commercially available, serum-free medium developed for adoptive immunotherapy, spontaneous secretion of superoxide by the monocytes was significantly higher than for monocytes elutriated in Hanks' balanced salt solution without calcium and magnesium or non-elutriated peripheral blood mononuclear cells. This stimulated state of the monocytes was observed both immediately after elutriation and after overnight storage at 4 degrees C, and it was not affected by the type of storage vessel used. Overnight storage of the monocytes at 37 degrees C resulted in a reversal of the stimulated state of the cells. Monocytes elutriated in XVIVO-10 and kept overnight at 4 degrees C released high amounts of arachidonic acid. A subsequent decrease in this release was seen after additional storage at 37 degrees C for 18 hours. These observations demonstrate that separation and storage variables have important effects on the state of stimulation of monocytes. Further investigations of such variables may suggest improved procedures for preparation and storage of these cells, as well as possible ways to stimulate monocytes prior to transfusion.     

Excess mortality following hip fracture: a systematic epidemiological review

Summary This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlighting the need for interventions to reduce this risk. Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess mortality rates for hip fracture. Although a lack of consistent study design precluded any formal meta-analysis or pooled analysis of the data, we have shown that hip fracture is associated with excess mortality (over and above mortality rates in nonhip fracture/community control populations) during the first year after fracture ranging from 8.4% to 36%. In the identified studies, individuals experienced an increased relative risk for mortality following hip fracture that was at least double that for the age-matched control population, became less pronounced with advancing age, was higher among men than women regardless of age, was highest in the days and weeks following the index fracture, and remained elevated for months and perhaps even years following the index fracture. These observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.     

Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p < 0.001), while the concentration of fibrinogen was lower in the HRT group than in the control group (3.02 g/l and 3.20 g/l, respectively; p < 0.001), indicating that it is unlikely that inflammation is the common underlying pathway. There was a significant interaction between smoking and HRT on the fibrinogen (p=0.02), but not on the CRP concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed in women using HRT; however, genetic polymorphisms in ESR1, CRP and FGB were not associated with these effects of HRT.     

The optimal anatomic sites for sampling heterosexual men for human papillomavirus (HPV) detection: the HPV detection in men study

Background. Human papillomavirus (HPV) infection in men contributes to infection and cervical disease in women as well as to disease in men. This study aimed to determine the optimal anatomic site(s) for HPV detection in heterosexual men.Methods. A cross-sectional study of HPV infection was conducted in 463 men from 2003 to 2006. Urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples were obtained. Samples were analyzed for sample adequacy and HPV DNA by polymerase chain reaction and genotyping. To determine the optimal sites for estimating HPV prevalence, site-specific prevalences were calculated and compared with the overall prevalence. Sites and combinations of sites were excluded until a recalculated prevalence was reduced by <5% from the overall prevalence.Results. The overall prevalence of HPV was 65.4%. HPV detection was highest at the penile shaft (49.9% for the full cohort and 47.9% for the subcohort of men with complete sampling), followed by the glans penis/coronal sulcus (35.8% and 32.8%) and scrotum (34.2% and 32.8%). Detection was lowest in urethra (10.1% and 10.2%) and semen (5.3% and 4.8%) samples. Exclusion of urethra, semen, and either perianal, scrotal, or anal samples resulted in a <5% reduction in prevalence.Conclusions. At a minimum, the penile shaft and the glans penis/coronal sulcus should be sampled in heterosexual men. A scrotal, perianal, or anal sample should also be included for optimal HPV detection.     

Spatial patterns of mercury in macroinvertebrates and fishes from streams of two contrasting forested landscapes in the eastern United States

Controls on mercury bioaccumulation in lotic ecosystems are not well understood. During 2007–2009, we studied mercury and stable isotope spatial patterns of macroinvertebrates and fishes from two medium-sized (<80 km²) forested basins in contrasting settings. Samples were collected seasonally from multiple sites across the Fishing Brook basin (FB_NY), in New York’s Adirondack Mountains, and the McTier Creek basin (MC_SC), in South Carolina’s Coastal Plain. Mean methylmercury (MeHg) concentrations within macroinvertebrate feeding groups, and mean total mercury (THg) concentrations within most fish feeding groups were similar between the two regions. However, mean THg concentrations in game fish and forage fish, overall, were much lower in FB_NY (1300 and 590 ng/g dw, respectively) than in MC_SC (2300 and 780 ng/g dw, respectively), due to lower trophic positions of these groups from FB_NY (means 3.3 and 2.7, respectively) than MC_SC (means 3.7 and 3.3, respectively). Much larger spatial variation in topography and water chemistry across FB_NY contributed to greater spatial variation in biotic Hg and positive correlations with dissolved MeHg and organic carbon in streamwater. Hydrologic transport distance (HTD) was negatively correlated with biotic Hg across FB_NY, and was a better predictor than wetland density. The small range of landscape conditions across MC_SC resulted in no consistent spatial patterns, and no discernable correspondence with local-scale environmental factors. This study demonstrates the importance of local-scale environmental factors to mercury bioaccumulation in topographically heterogeneous landscapes, and provides evidence that food-chain length can be an important predictor of broad-scale differences in Hg bioaccumulation among streams.     

Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: The Danish Osteoporosis Prevention Study.

Assessing bone loss and gain is important in clinical decision-making, both in evaluating treatment and in following untreated patients. The aim of this study was to correlate changes in bone mineral density (BMD) at different skeletal sites during the first 5 years after menopause and determine if forearm measurements can substitute for dual-energy X-ray absorptiometry (DXA) of the spine and hip. BMD was measured at 0, 1, 2, 3, and 5 years using Hologic 1000/W and 2000 densitometers in 2,016 perimenopausal women participating in a national cohort study. This analysis comprises 1,422 women remaining in the study after 5 years without changes to their initial treatment (hormone-replacement therapy [HRT], n = 497, or none, n = 925). Despite correlated rates of change between forearm and spine (r2 = 0.11; p < 0.01), one-half of those who experienced a significant decrease in spine BMD at 5 years showed no significant fall in forearm BMD (sensitivity, 50%; specificity, 85%; kappa = 0.25). The total hip had significant better agreement with spine (sensitivity, 63%; specificity, 85%; kappa = 0.37; p < 0.01). Analysis of quartiles of change also showed significant better agreement with spine and whole body for the total hip than for the femoral neck or ultradistal (UD) forearm. In a logistic regression analysis for identification of group (HRT or control), the prediction was best for whole body (82.6%) and spine (80.9%), followed by total hip (78.5%) and forearm (74.7%). In conclusion, changes at the commonly measured sites are discordant, and DXA of the forearm is less useful than DXA of the hip or spine in determining the overall skeletal response to therapy or assessing bone loss in untreated women.