Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults

OBJECTIVES: To define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease. DESIGN: This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years). METHODS: Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression. RESULTS: A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9). CONCLUSION: Over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression.     

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

Use of Density-Equalizing Cartograms to Visualize Trends and Disparities in State-Specific Prevalence of Obesity: 1996–2006

Objectives. We used cartograms to visually communicate the state-specific prevalence of obesity and its association with socioeconomic variables over time to benefit and inform decisions by national health policymakers who address geographic and social inequities in health.Methods. We generated density-equalizing maps, known as cartograms (in which geographic regions are sized in proportion to some variable), that illustrate indicators of population and educational attainment. We also provide an innovative presentation of the obesity choropleth map (which presents values for areas by shading).Results. The maps depict the absolute burden of obesity, the inverse association between obesity and education, and geographic patterns in the prevalence of obesity over time.Conclusions. The prevalence of obesity in the United States continues to increase. These cartograms can help stakeholders interpret surveillance data and their relation to demographic and socioeconomic characteristics to inform decisions.Several national surveys have shown that prevalence rates for obesity continue to increase.^1,2 Not surprisingly, this prevalence is not uniformly distributed; obesity disproportionately affects some groups in the United States.^3,4 Among adult men, no significant differences in obesity prevalence are seen among racial/ethnic groups.^1,5,6 However, both non-Hispanic Black and Mexican American women have a higher prevalence of obesity.^1,5,6 Among adult women, poverty and low educational levels are also associated with a higher prevalence of obesity.⁵Data from public health surveillance, often summarized in large, traditional tables, can be difficult to interpret and may not show the information in a meaningful way. One common solution is to display trends in the prevalence of obesity via maps. For instance, researchers have used choropleth maps (which present percentages for areas through the use of color, saturation, and lightness) to show changes in state-specific prevalence of obesity over time.⁷ Several limitations and critiques have been noted for choropleth maps, however.^8,9 For example, large areas (often sparsely populated) tend to visually dominate smaller (often densely populated) areas,^10–14 leading to potential misinterpretation of the burden of obesity. Moreover, obesity is most highly concentrated among certain subpopulations, not only minorities but also the poor,¹⁵ and these related factors are difficult to depict on choropleth maps.The use of density-equalizing maps, or cartograms, minimizes such limitations by transforming the size and sometimes the shape of political areas (in this case, states) so they are proportional to another variable; traditionally, the variable is population, but other variables could be used. Cartograms are relatively new to public health but have been used successfully to map patterns of chronic disease, including the distribution of Wilms tumors in New York State,¹⁶ mortality patterns of cerebrovascular disease in North Carolina,¹⁷ and associations between both lung cancer and leukemia and the Rocky Flats plant site in Colorado.¹⁰ Other successful cartograms have been developed to analyze the spatial distribution of cryptosporidiosis among AIDS patients in San Francisco, California,¹⁸ and to characterize the spatial distribution of late-state and in situ breast cancer among women in the San Francisco Bay Area.¹⁹ Innovative mapping applications, including cartograms, can be used in public health to improve understanding of health problems and for exploratory analysis of data.^20,21For our exploratory study, we used cartograms and other cartographic techniques to visually communicate the pattern of obesity prevalence and its association with socioeconomic variables over time. Our density-equalizing cartograms of population and education indicators show the prevalence of obesity, and an innovative presentation of the choropleth map shows change in obesity prevalence over time.     

Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Objective

Indexes of brain serotonin_2A (5-HT_2A) density have never been investigated in a sample of humans with violent aggressive behaviour unbiased by medication use or current axis I psychiatric disorders. The objective of this study was to investigate prefrontal cortex 5-HT_2A binding potential (BP_ND), an index of 5-HT_2A density, in an unbiased sample of people with violent aggressive behaviour.

Methods

We used [¹⁸F] setoperone positron emission tomography to measure 5-HT_2A BP_ND in the dorsolateral prefrontal cortex (primarily sampling Brodmann area 9) in 16 participants with violent aggressive behaviour and 16 healthy control participants.

Results

In people with violent aggressive behaviours, the slope of 5-HT_2A BP_ND decline in the dorsolateral prefrontal cortex is 44% less than in healthy control participants (analysis of variance group by age interaction, p = 0.004). Prefrontal cortex 5-HT_2A BP_ND was significantly lower in participants with more severe impulsivity and aggression (multiple linear regression with age and Barratt Impulsivity Scale [BIS] as predictor variables and regional 5-HT_2A BP_ND as dependent variable; effect of BIS, dorsolateral prefrontal cortex: F_1,13 = 7.95, p = 0.014).

Conclusion

Lower prefrontal 5-HT_2A BP_ND is related to violent aggression. Lower 5-HT_2A BP_ND occurs at a younger age, when violent behaviour is more frequent, and is more prominent when impulsivity and aggression are more severe.Medical subject headings: aggression, serotonin, receptors, serotonin, 5-HT_2A, positron emission tomography, setoperone, suicide     

Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration

Binding of (+)-[11C]DTBZ (dihydrotetrabenazine) to the striatal vesicular monoamine transporter (VMAT2) is widely considered to be a stable marker of dopamine neurone integrity. However, we now find that specific binding of a tracer dose of (+)-[11C]DTBZ is modestly increased in rat striatum following dopamine depletion with alpha-methyl-p-tyrosine (alpha-MPT, +14%) or d-amphetamine (d-AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation with gamma-hydroxybutyrate (GHB, -16%) or levodopa (-20%). We suggest that in vivo (+)-[11C]DTBZ binding in imaging studies is subject to competition by vesicular dopamine and, in this respect, is not a "stable" dopamine biomarker as is generally assumed.     

Fluticasone furoate nasal spray: effective monotherapy for symptoms of perennial allergic rhinitis in adults/adolescents.

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The purpose of this study was to evaluate the efficacy and tolerability of intranasal fluticasone furoate, a novel enhanced-affinity glucocorticoid, in patients > or =12 years of age with PAR in a global, randomized, double-blind, placebo-controlled, 6-week study. Patients (n = 302) received fluticasone furoate nasal spray (FFNS) 110 microg or vehicle placebo once daily (q.d.). The primary efficacy measure was mean change from baseline over the 6-week treatment period in daily reflective total nasal symptom score (TNSS). Secondary end points included mean change from baseline in total and individual reflective nasal and ocular symptom scores and in daily peak nasal inspiratory flow (PNIF). FFNS was significantly more effective than placebo in reducing daily reflective TNSS over the treatment period (least square [LS] mean difference, -1.256; p < 0.001). Significant improvements were also established in total ocular symptom score (LS mean difference, -0.506; p = 0.004 versus placebo) and in all individual nasal (p < 0.001) and ocular (p < 0.03) symptoms assessed in a reflective manner. Improvements in daily PNIF were significantly greater with FFNS than placebo (LS mean difference, 8.376 L/minute; p = 0.004). FFNS was well tolerated. In this study, FFNS 110 microg q.d. was well tolerated and effective in reducing the nasal and ocular symptoms of PAR in adult and adolescent patients > or =12 years of age.     

人脂肪组织来源干细胞在心脏疾病治疗中的应用

目的:综述人脂肪组织来源干细胞的生物学特性及其在缺血性心脏病中的应用,分析不足,并在此基础上提出未来研究要解决的问题,以期为临床治疗提供依据。资料来源:应用计算机检索Blackwell、Elsevier、Pubmed数据库1980/2007期间脂肪源性干细胞与缺血性心脏病方面的文献,检索词为“bone mesenchymal stem cells,adipose derived stemcells,cardiomyocytes,ischemic heart disease”等。应用计算机检索中国期刊全文数据库1980/2007期间相关文献,检索词为“骨髓间充质干细胞,脂肪组织来源的干细胞,心肌细胞,缺血性心脏病”等。并手工查阅相关书籍。资料选择:对资料进行初步选择:①脂肪组织来源干细胞的生物学特性。②脂肪组织来源干细胞治疗缺血性心脏病。排除重复文献。资料提炼:共搜集到相关文章57篇,删除内容重复及与本文主题关系较远的文章,剩余41篇作为综述参考。资料综合:脂肪组织来源干细胞与同样起源于中胚层的骨髓基质细胞不仅具有非常相似的生物学特性,而且在细胞表面标志谱的表达方面也非常相近。并且脂肪组织来源广泛,取材方便,可获得的基质细胞数量大,易于培养扩增。有研究发现,脂肪组织来源干细胞体外培养不需要任何诱导便能分化成具有自律性的心肌细胞,使得脂肪组织来源干细胞治疗缺血性心脏病成为可能。结论:脂肪组织来源干细胞在取材和增殖方面较骨髓间充质干细胞有优势;脂肪组织来源干细胞能较好的诱导为心肌细胞,将为缺血性心脏病的治疗提供更广阔的前景。     

A new combined in-vitro test model for the identification of substances affecting essential sperm functions [published erratum appears in Hum Reprod 1997 Nov;12(11):2580]

Binding of mammalian spermatozoa to the zona pellucida and the induction of the acrosome reaction are prerequisites for successful oocyte fertilization. It has been postulated that xenobiotics that are released in the environment as well as exposure to pharmaceutical medications may be associated with reproductive problems in men and wildlife. Examining physiological and non-physiological effects of particular compounds on sperm functions requires high quality in-vitro test systems. We established a reliable combined in-vitro test system with bovine gametes and evaluated if aliquots of pooled post-thaw spermatozoa are suitable for examining essential sperm functions. Using cryopreserved semen, the PSA-FITC/Hoechst 33258 staining procedure was applicable to evaluate the acrosomal status and cell viability. In the bovine hemizona assay, hemizona indices revealed no differences between cryopreserved and fresh semen. Treatment of post-thaw bovine spermatozoa with progesterone (1 microM or bovine follicular fluid (20%) induced the acrosome reaction from 12% (untreated spermatozoa) to 25% (P < 0.001) and to 22% [corrected] (P < 0.01), respectively. Incubation of both compounds (1 microM progesterone and 20% follicular fluid) raised the percentage of acrosome-reacted spermatozoa to 30% (P < 0001). Our results demonstrate that cryopreserved semen can be integrated into an in-vitro screening model for reproductive toxicology testing. Pooled, cryopreserved bovine spermatozoa will thus permit reproducible experiments for clinical and basic science purposes and may also be applicable for the human system.