A recombinant fusion protein derived from dog hookworm inhibits autoantibody-induced dermal-epidermal separation ex vivo.

The proteins secreted by parasitic nematodes are evolutionarily optimized molecules with unique capabilities of suppressing the immune response of the host organism. Neutrophil inhibitory factor (NIF), which is secreted by the dog hookworm Ancylostoma caninum, binds to the ß2 integrin CD11b/CD18, which is expressed on human neutrophils, eosinophils, monocytes and macrophages and inhibits neutrophil-dependent lung injury and neutrophil invasion of ischaemic brain tissue. Neutrophils are key players in the pathogenesis of subepidermal autoimmune blistering diseases (sAIBDs), and their pathogenic activities are crucially dependent on ß2 integrin functionality. Based on the template of single-stranded, dimerizing antibody derivatives, which are already used in cancer treatment, we designed a novel biologic, NIF-IGHE-CH4, comprising NIF and the dimerizing but otherwise inert constant heavy subdomain 4 (CH4) of human IgE (IGHE). This molecule was evaluated in a variety of in vitro assays, demonstrating its ability to inhibit pathogenically relevant neutrophil functions such as migration, adhesion and spreading, and release of reactive oxygen species. Finally, we confirmed that NIF-IGHE-CH4 inhibits blister formation in an ex vivo assay of sAIBD. These results suggest that NIF-IGHE-CH4 is a novel potential anti-inflammatory drug for the treatment of neutrophil-mediated diseases such as sAIBDs. This study promotes the drugs from bugs concept and encourages further research and development focused on turning parasite proteins into useful anti-inflammatory biologics.

Use of a surgical specimen-collection kit to improve mediastinal lymph-node examination of resectable lung cancer.

INTRODUCTION: Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non-small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non-small-cell lung cancer by using a prelabeled specimen-collection kit. METHODS: Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. RESULTS: The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. CONCLUSIONS: The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.

National trends in surgical therapy for benign prostatic hyperplasia in the United States (2000-2008).

OBJECTIVE: To report an update of the change in usage trends for different surgical treatments of benign prostatic hyperplasia (BPH) among the United States Medicare population data from 2000-2008. The rate of usage of thermotherapy and laser therapy in the surgical treatment of BPH has been changing over the past decade in conjunction with a steady decrease of transurethral resection of the prostate (TURP). METHODS: Using the 100% Medicare carrier file for the years 2000-2008, we calculated counts and population-adjusted rates of BPH surgery. Rates of TURP, thermotherapy, and laser-using modalities were calculated and compared in relation to age, race, clinical setting, and reimbursement. RESULTS: After years of a steady rise, the total rate of all BPH procedures peaked in 2005 at 1078/100,000 and then declined by 15.4% to 912/100,000 in 2008. TURP rates continued to decline from 670 in 2000 to 351/100,000 in 2008. Rates of microwave thermoablation peaked in 2006 at 266/100,000 and then declined 26% in 2008. Laser vaporization almost completely replaced laser coagulation and in 2008 was the most commonly performed procedure second to TURP, with the majority performed as outpatient procedures (70%) and an increasing percentage in the office (12%). Men between ages 70 and 75 had the highest rate of procedures. Reimbursement rates correlate using some but not all procedures. Racial disparities reported previously appear to have resolved. CONCLUSION: Surgical treatment of BPH continues to change rapidly. TURP continues to decline and laser vaporization is the fastest growing modality. There is a big shift toward outpatient/office procedures. Reimbursement rates do not appear to have a consistent effect on usage.

[Study on inhibitive effect of extracts from Scindapsus aureus on alpha-glucosidase and its antioxidant activity].

OBJECTIVE: To study the inhibitive effect of extracts from Scindapsus aureus on alpha-glucosidase and its antioxidant activity. METHODS: The 70% ethanol extracts was extracted by petroleum, ethyl acetate and n-butanol, and the inhibitory activity against alpha-glucosidases and antioxidative effects of each fraction were determined in vitro, and the inhibitory kinetics of ethyl acetate fraction was investigated. RESULTS: The inhibitory activity of ethly acetate fraction against alpha-glucosidase was higher as its IC50 was 43.63 microg/mL. The inhibition kinetics analyzed by Hnewaver-Burk plots showed that ethyl acetate fraction was a competitive type inhibitor, and the inhibition constants for free ennzyme (Ki) was determined to be 21.49 microg/mL. The antioxidative effects of ethly acetate and n-butanol fractions exhibited stronger than that of other fractions, the scavenging ability on DPPH at the concentration of 0.42 mg/mL were 88.5% and 93.6%. Ethly acetate fraction showed scavenging ability on autioxidantor, and the IC50 values was 0.27 mg/mL. CONCLUSION: Ethyld acetate fraction of extract from Scindapsus aureus has potential inhibitroy activity against alpha-glucosidase and antioxidant effects, and n-butanol fraction has great antioxidative effects.

Practice patterns in benign prostatic hyperplasia surgical therapy: the dramatic increase in minimally invasive technologies.

PURPOSE: We describe the trends in transurethral prostatectomy and minimally invasive surgical treatments for benign prostate hyperplasia from 1999 through 2005 among elderly male Medicare beneficiaries. MATERIALS AND METHODS: Benign prostatic hyperplasia surgeries were identified using the annual 100% Medicare carrier files which contain physician claims for services reimbursed under Medicare Part B. The annual age group specific procedure rates as well as the age adjusted rates by race and percent of each procedure performed in different clinical settings were calculated. RESULTS: The total number of benign prostatic hyperplasia procedures increased 44% from 88,868 in 1999 to 127,786 in 2005. The minimally invasive surgical treatment procedure counts increased 529% from 11,582 to 72,887 and the rates increased 439% from 136 to 678 per 100,000 males during that period. The transurethral prostate resection rate decreased approximately 5% per year. By 2005 minimally invasive surgical treatment procedures accounted for 57% of total benign prostatic hyperplasia surgeries, while transurethral prostate resection accounted for only 39%. Almost all transurethral microwave thermotherapy, 86% of transurethral needle ablation and 54% of laser coagulation procedures were performed in office clinics, and 78% of laser vaporization procedures were performed in hospital outpatient clinics. Black beneficiaries were 17% less likely to receive minimally invasive surgical treatment than whites in 2005. CONCLUSIONS: The increase of total benign prostatic hyperplasia procedure rate was driven by a marked increase in minimally invasive surgical treatment and a continuing decrease of transurethral prostate resection. Differences in the use of minimally invasive surgical treatment across age and racial groups persisted. This dramatic change in the pattern of benign prostatic hyperplasia surgical treatment may have a profound impact on health care expenditures and outcomes, and requires further investigation.

[Inhibition of extracts from Synotis erythropappa on tyrosinase].

OBJECTIVE: To study the inhibition of extracts from Synotis erythropappa on tyrosinase. METHODS: The 70% ethanol extracts were extracted by petroleum benzine, ethyl acetate and n-butanol, and the inhibitory activities against tyrosinase of every fraction were determined in vitro and the inhibitory kinetics of ethyl acetate and n-butanol fractions were investigated. RESULTS: The four fractions extracted all had inhibitory activities on tyrosinase, inhibitory activities of ethyl acetate and n-butanol fraction were higher. Their IC50 were 57.8, 140 microg/ml for monophenol oxidase activity and 41.2, 59.6 microg/ml for diphenol oxidase activity, respectively. The inhibition kinetics analyzed by Hnewaver-Burk plots showed that ethyl acetate fraction was a competitive type inhibitor, and its Ki was determined to be 19.7 microg/ml. n-butanol fraction was an uncompetitive type inhibitor, and its Ki was determined to be 60.7 microg/ml. CONCLUSION: Ethyl acetate and n-butanol fractions of extracts from Synotis erythropappa show potential inhibitory activity on tyrosinase.

Unequal use of new technologies by race: the use of new prostate surgeries (transurethral needle ablation, transurethral microwave therapy and laser) among elderly Medicare beneficiaries.

PURPOSE: We compared the availability and use of transurethral microwave therapy, transurethral needle ablation, contact or noncontact laser therapy and transurethral resection of the prostate among elderly black and white Medicare beneficiaries. MATERIALS AND METHODS: We examined 100% Medicare Inpatient, Outpatient, Carrier and Denominator files of men 65 years old or older who underwent these procedures in 1999 through 2001. White-to-black race rate ratios for each procedure were computed for the entire United States, as well as for a restricted set of counties in which procedures were available to black beneficiaries. RESULTS: A total of 170,067 TURP, 16,953 TUMT, 5,353 TUNA and 12,134 Laser procedures were performed during 3 years. Nationally there was only a 3% difference in the age adjusted TURP rates between white and black men (6.13 and 5.94 per 1,000 person-years, respectively). However, the age adjusted rates for TUMT and TUNA among white men were about twice those among black men (0.63 vs 0.31 and 0.20 vs 0.10 per 1,000 person-years, respectively). Laser rates were 17% higher among white men than among black men (0.44 vs 0.38 per 1,000 person-years). Large geographic variation existed in the new procedure rates. Negative binomial regression analysis confirmed the national findings in those counties in which the procedures were available to black men. Adjusted white-to-black rate ratios were 1.96 (95% CI 1.70-2.25) for TUMT, 2.33 (95% CI 1.87-2.90) for TUNA and 1.36 (95% CI 1.16-1.59) for Laser. CONCLUSIONS: After controlling for availability, elderly black Medicare beneficiaries were less likely to undergo the new BPH procedures than white beneficiaries, while the usage difference for TURP remained small.

Plasma F2-isoprostanes and coronary artery calcification: the CARDIA Study.

BACKGROUND: Oxidation of lipids in lipoproteins and cells may initiate and enhance the early development of cardiovascular disease. METHOD AND RESULTS: We assayed F(2)-isoprostanes, oxidation products of arachidonic acid, by gas chromatography-mass spectrometry in a biracial cohort of 2850 young healthy adult men and women. Coronary artery calcification (CAC), a component of coronary artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in its initial stages (Agatston scores <20 in 47% and <100 in 83% of CAC-positive participants). After adjusting for sex, clinical site, age, and race, the presence of any CAC was 24% more likely among those with high vs low concentrations of F(2)-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7 ng/L; 1 SD of F(2)-isoprostanes); 95% confidence interval (CI), 1.09-1.41]. The OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02-1.38] after further adjustment for body mass index, smoking, serum lipids, C-reactive protein, antioxidant supplementation use, diabetes, and blood pressure. As a continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7 ng/L) of F(2)-isoprostane concentration (P <0.01). Whereas CAC prevalence was lower in women than men, mean (SD), F(2)-isoprostanes were higher in women {190 (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7) ng/L]}. Nevertheless, F(2)-isoprostanes were associated with an increased risk of CAC in both sexes. CONCLUSION: This association between increased concentrations of circulating F(2)-isoprostanes and CAC in young healthy adults supports the hypothesis that oxidative damage is involved in the early development of atherosclerosis.

Lipid standardization of serum fat-soluble antioxidant concentrations: the YALTA study.

BACKGROUND: Blood lipids can influence fat-soluble antioxidant concentrations and confound their interpretation as indicators of antioxidant intake status and disease risk. OBJECTIVES: The objectives were to identify lipoproteins that can confound the interpretation of serum fat-soluble antioxidants, to evaluate the amount of the confounding, and to recommend a method for standardizing blood concentrations of fat-soluble antioxidants. DESIGN: Several methods of lipid standardization of fat-soluble antioxidants were evaluated in a large cohort of young adults with the use of both cross-sectional and longitudinal data analysis. RESULTS: Tocopherol and carotenoid concentrations were associated with plasma total cholesterol and its components, LDL, HDL, and VLDL cholesterol (estimated as plasma total triacylglycerols/5), some of which were independent predictors for all of the fat-soluble antioxidants. Among supplement nonusers, the most amphipathic (polar) of the antioxidants (alpha-tocopherol, gamma-tocopherol, and zeaxanthin plus lutein) and lycopene were associated strongly with these lipid fractions (R(2) = 0.09, 0.40). Consistent with a causal association in which blood antioxidant concentrations change as blood lipid concentrations change, similar relations were found for changes in blood antioxidant and lipid concentrations over a 7-y period. Concentrations of the remaining carotenoids (beta-cryptoxanthin, alpha-carotene, and beta-carotene) had a weaker association with plasma lipoproteins (R(2) < 0.06). Similar relations were found for supplement users. CONCLUSIONS: The simultaneous adjustment of the concentrations of tocopherols, zeaxanthin plus lutein, and lycopene for VLDL, HDL, and LDL cholesterol is recommended. This method is practical and can provide a basis for the standardization of carotenoid and tocopherol concentrations.