bluuebunny/crossref_metadata_2025 huggingface dataset:
Limestone Treatment of Whetstone Brook, Massachusetts. III. Changes in the Invertebrate Fauna
Authors: Simmons Kenneth R. , Doyle Katheryn
Published: April 2006

We monitored the invertebrate fauna in Whetstone Brook for 3 years before and after limestone treatment to mitigate low pH conditions caused by acid precipitation. Sampling was conducted during the spring, summer, and fall by both qualitative and quantitative methods. The fauna in Whetstone Brook in the control and treatment sections was dominated by chironomids (Diptera), simuliids (Diptera),Leuctra(Plecop‐tera) andHydropsyche(Trichoptera) in both pretreatment and treatment periods. The acid‐sensitive mayfly generaEpeorusincreased during liming in the treated section of the stream but also declined during the same period in the control section. Annelida increased during the treatment period in both sections of the stream. The chironomid and black fly populations were not affected by liming. The lack of impact to the black fly population was surprising because larvae are obligate filter‐feeders and feed on suspended seston in the same size range as the limestone slurry that was used to treat Whetstone Brook. Treatment did not change species diversity and taxa richness in the treated section of Whetsone Brook, but both indices declined during the treatment period in the control section of Whetstone Brook. This decline was attributed to the poorer water quality of the untreated section of Whetstone Brook during the treatment period, which was due to higher‐than‐average precipitation. Percent community similarity analysis indicated that the community composition changed more in the treated section of Whetstone Brook than in the control section as a result of treatment. We conclude that the invertebrate fauna in the treated section of Whetstone Brook was not negatively affected by liming, but that population density and diversity did not increase.
Changes in Aquatic Macrophytes after Liming Thrush Lake, Minnesota
Authors: Hagley Cynthia A. , Wright David , Owen Christopher J. , Eiler Paul , Banks Marilyn
Published: April 2006

Thrush Lake, Minnesota, was treated with limestone in 1988 to evaluate the efficacy of protective base addition against the loss of sport fisheries in a sensitive, mildly acidic lake. Prior to treatment, the lake was stressed (pH 6.46, ANC 64 μeq/L) but not severely degraded by acidic deposition and had a macrophyte community typical of lakes in northeastern Minnesota with low acid‐neutralizing capacity (ANC). This paper describes the changes observed in aquatic plant communities during the 5 years after treatment, as pH and ANC slowly returned to pretreatment levels. Sphagnum platyphyllum, intolerant of non‐acid conditions, was completely eliminated from the lake. The charo‐phyte, Nitella, that originally shared dominance in the deep littoral zone with S. platyphyllum, decreased in importance during the first 2 years after treatment. Two vascular plants, Potamogeton pusillus and Najas flexilis, were first found in the lake the year after treatment and were abundant for 2 years after liming, probably in response to a combination of more neutral pH and reduced cover of Nitella. As the ANC and pH slowly returned to pretreatment conditions, Nitella again increased in coverage and depth range, with a concomitant decrease in P. pusillus and N. flexilis. The moss, S. platyphyllum, had not reinvaded the lake by 1993, 2 years after its dramatic decline.
Physiological Performance of Andropogon gerardii, Panicum virgatum, and Sorghastrum nutans on Reclaimed Mine Spoil
Authors: Skeel Virginia A. , Gibson David J.
Published: April 2006

Physiological and vegetative performances of three prairie grasses were investigated to assess their adaptation to soil conditions at two strip mine sites and a nearby railroad prairie. Additionally, rhizomes of the species were transplanted to a pot experiment and grown in both field soil and greenhouse potting medium to investigate the extent to which plants are limited under field conditions. Field measurements of photosynthetic rate and stomatal conductance to water vapor were made on the three species monthly from May to late August. Gas exchange measurements on potted plants were made biweekly from early May to mid‐July. In September, vegetative and flowering characteristics were measured on both field and potted plants. Field gas exchange rates were highest at one of the mines. Sorghastrum nutans had the highest rates at the mine sites, whereas Panicum virgatum had the highest rates at the prairie site. Potted plants from the prairie site usually exhibited the highest gas exchange rates, and Sorghastrum nutans had higher rates than Panicum virgatum and Andropogon gerardii. Potted plants in field soil generally had higher gas‐exchange rates than plants growing in greenhouse potting medium, and potted plants had higher gas‐exchange rates than field‐grown plants. Vegetative and reproductive performance of field plants was highest at one of the mine sites. Potted plants in greenhouse medium had up to twice the vegetative and reproductive output as potted plants in field soil or plants growing in the field. The physiological and vegetative performance of these species indicates that they are well adapted to the soil conditions at these strip mine sites, and that they are a viable alternative to nonnative plantings for restoration.
Vital Landscape Attributes: Missing Tools for Restoration Ecology
Authors: Aronson James , Le Floc'h Edouard
Published: April 2006

Twenty‐three “vital ecosystem attributes” (VEAs) were previously proposed to aid in quantitative evaluation of whole ecosystem structure, composition, and functional complexity over time. We here introduce a series of 16 quantifiable attributes for use at a higher spatial scale and ecological organizational level, the landscape. “Vital landscape attributes” (VLAs) should be useful in evaluating the results of ecological restoration or rehabilitation undertaken with a landscape perspective, provided that clear definitions and boundaries are agreed upon for the different spatial and ecological entities involved. Like VEAs, VLAs should be sensitive to changes wrought by human as well as to nonhuman factors leading to ruptures in flow processes or vegetation “switches.” They should be applicable over a wide range of landscape types and therefore aid in conducting rigorous interlandscape comparisons. We present three groups of VLAs: (1) landscape structure and biotic composition, (2) functional interactions among ecosystems within the landscape, and (3) degree, type, and causes of landscape fragmentation and degradation. Ecotones between ecosystems are touched upon by several different VLAs. Because conflicting terminology abounds in this area, we append a glossary defining the problematic terms used.
Control of Legumes in a Species‐Rich Meadow Re‐created on Land Restored after Opencast Coal Mining
Authors: Chapman R. , Collins J. , Younger A.
Published: April 2006

Aggressive growth by legumes may restrict the diversity of species‐rich meadows recreated on sites restored after mineral extraction. We investigated the ability of mineral nitrogen (N) applications and spring grazing to control the legume component of such meadows. The use of N suppressed Trifolium repens but had no effect on other legume species or on the species richness, diversity, or equitability of the meadow community. Spring grazing significantly reduced the yield from the legume component of the meadow. This was accompanied by an increase in the equitability index of the community, suggesting that the aggressive nature of the legumes had been checked. Spring grazing may therefore provide a means of controlling aggressive legume growth and may maintain the diversity of species‐rich meadows established on restored sites.
Influence of Campsites on Black Bear Habitat Use and Potential Impact on Caribou Restoration
Authors: Pitt William C. , Jordan Peter A.
Published: April 2006

Ursus americanus(black bear) predation could limit the success of the proposed restoration ofRangifer tarandus(woodland caribou) to Minnesota. The problem was recently identified as a major factor in the failure of a similar restoration effort in Maine. During the summer of 1991 we conducted a survey in the region of the proposed restoration, using bait stations to identify bear presence. Four settings were sampled: islands with campsites, islands without campsites, mainland areas with campsites, and mainland areas without campsites. Results from the survey suggest that black bears use areas with campsites more than those without. Whereas caribou may use islands preferentially for calving to escape predation, islands with campsites may be unfavorable for caribou calf survival due to frequent bear visitation.
Association between serum albumin and periodontal disease in community‐dwelling elderly
Authors: Ogawa Hiroshi , Yoshihara Akihiro , Amarasena Najith , Hirotomi Toshinobu , Miyazaki Hideo
Published: April 2006

Aim: The purpose of this study was to evaluate the relationship between periodontal disease and general health status in community‐dwelling elderly using serum albumin concentration as a criterion index of the severity of an underlying disease and nutrition status.

Methods: Serum albumin level was detected by the bromcresol green albumin (BCG) method and the data for serum albumin were available in 368 subjects aged 75 years. Pressure‐sensitive probes were used to measure loss of attachment (LA) on six sites of all teeth present. Information relevant to gender and smoking habit was obtained by means of a personal interview, while body mass index (BMI) and biochemical serum markers were investigated.

Results: Serum albumin concentration ranged from 3.2 to 4.8 g/dl with a mean of 4.1±0.2. More than 70% of subjects had at least one site with LA 6+ mm, while 91 exhibited 10% or more sites with LA 6+ mm. Using a multiple regression analysis, we found that sites of LA 6+ mm had a significant effect on serum albumin level (correlation coefficient=−0.14; p<0.05), which was independent of the other covariates.

Conclusions: The findings of the present study indicated that there might be an inverse relationship between periodontal disease and serum albumin concentration in these elderly subjects.
Is there a relationship between juvenile idiopathic arthritis and periodontitis?
Authors: Reichert Stefan , Machulla Helmut K. G. , Fuchs Corinna , John Vera , Schaller Hans‐Günter , Stein Jamal
Published: April 2006

Aim: The aim was to compare the prevalence of periodontal conditions in patients with juvenile idiopathic arthritis (JIA) (n=78, age 14.4 years) with those revealed in a healthy control group (n=75, age 15.5 years).

Material and Methods: In both groups, the approximal plaque index (API), the modified sulcular bleeding index (SBI), and the clinical attachment loss (CAL) were determined. Laboratory parameters for JIA activity included the capsule‐reactive protein (CRP) and the immunoglobulins A, G, M.

Results: JIA patients had a significantly higher API (64.6%versus 49.9%, p=0.004) and slightly higher mean percentages of sites with CAL>3.5 mm (0.58%versus 0.22%, p=0.041). There was no significant difference in the prevalence of patients and controls who had sites with CAL >3.5 mm (25.6%versus 17.3%, p=0.212). The mean CAL was slightly greater (0.2 mm; p=0.030) in patients with CRP5.0 mg/l compared with patients with CRP<5.0 mg/l. Patients who took non‐steroidal anti‐inflammatory drugs (NSAIDs) had a significantly decreased SBI (26.2%versus 51.1%, p=0.019).

Conclusion: After adjustment for microbial plaque, JIA is not a risk factor for periodontitis.
Time as a factor in the identification of subjects with different susceptibility to plaque‐induced gingivitis
Authors: Trombelli Leonardo , Scapoli Chiara , Calura Giorgio , Tatakis Dimitris N.
Published: April 2006

Objectives: The purpose of this study was to assess whether identification of subjects with different susceptibility to plaque‐induced gingival inflammation is dependent on the length of time of de novo plaque accumulation.

Methods: Retrospective analysis of data obtained from a recently reported (J Clin Periodontol31, 239, 2004) randomized split‐mouth localized experimental gingivitis trial involving 96 healthy non‐smokers. Gingival and plaque index, gingival crevicular fluid volume (GCF), angulated bleeding score, and the derived parameter cumulative plaque exposure (CPE) were recorded at days 0, 7, 14, and 21. The primary outcome variable to express severity of inflammation was GCF and each subject was a statistical unit. Based on subject distribution of GCF‐day 21 residuals after standardization for CPE‐day 21, two sub‐populations (upper and lower distribution quartiles) were selected. They were, respectively, defined as “high responders” (HR) (n=24) and “low responders” (LR) (n=24) and characterized by significantly different severity of gingivitis to similar amounts of plaque deposits. The same analysis was repeated at days 7 and 14. Prevalence of HR and LR was compared between days using the χ2 [ML] test.

Results: For both day 7 and day 14, the quartile distribution of LR and HR was statistically significant (p=0.02). Fifty percent of LR and 71% of HR presented a consistent level of susceptibility to plaque‐induced gingival inflammation even after only 7 and/or 14 days of plaque accumulation.

Conclusions: These findings support the concept that the subject‐based susceptibility to plaque‐induced gingival inflammation is an individual trait, only partly related to the length of time of exposure to plaque.
Persistence of Helicobacter pylori in the oral cavity after systemic eradication therapy
Authors: Gebara E. C. E. , Faria C. M. , Pannuti C. , Chehter L. , Mayer M. P. A. , Lima L. A. P. A.
Published: April 2006

Aim: The present study aimed to evaluate if the oral cavity of chronic periodontitis patients can harbor Helicobacter pylori after systemic eradication therapy.

Materials and Methods: Samples of 30 patients (15 with gingivitis and 15 with chronic periodontitis) positive for H. pylori in the stomach were evaluated. Samples were collected 3 months after triple systemic antibiotic therapy from saliva, microbiota from the dorsum of the tongue, supra‐ and sub‐gingival plaque as well as gastric biopsies. DNA of each sample was extracted by the boiling method and used as a template in polymerase chain reaction with the primers JW22/23.

Results: Eighteen patients (60%) harboured H. pylori in their mouths. Five patients (16.6%) were positive in saliva, two (6.6%) on the dorsum of the tongue, nine (30%) in supra‐gingival plaque, 14 (46.6%) in sub‐gingival plaque and three (10%) in the stomach. There was no statistically significant difference between study groups.

Conclusion: Eradication of H. pylori after therapy was more effective for the stomach than for the mouth (p<0.001). Mouths of patients with gingivitis or with chronic periodontitis, who are positive for H. pylori in their stomachs, may be considered as reservoirs of these bacteria.
Differences in efficacy of two commercial 0.2% chlorhexidine mouthrinse solutions: a 4‐day plaque re‐growth study
Authors: Arweiler Nicole B. , Boehnke Nils , Sculean Anton , Hellwig Elmar , Auschill Thorsten M.
Published: April 2006

Background: The purpose of this clinical cross‐over study was to examine the antibacterial and plaque‐inhibiting properties of two chlorhexidine solutions compared with a negative control.

Material and Methods: Twenty‐one volunteers refrained from all oral hygiene measures, but rinsed instead twice daily with 10 ml of a conventional chlorhexidine solution (0.2%; CHX), a chlorhexidine solution with anti‐discolouration system (ADS) (0.2%, alcohol‐free chlorhexidine solution (CSP)) or a placebo solution (Pla). Plaque index (PI), plaque area (PA) and bacterial vitality were assessed after 24 h (PI1, vital flora (VF)1) and 96 h (PI2; VF2, PA). After a 10‐day wash‐out period, a new test cycle was started.

Results: Results for Pla were 0.94, 1.59, 27.4 (PI1, PI2, PA) and 79% and 72% (VF1 and VF2). CSP significantly reduced the parameter PI1, PI2 and PA to 0.67 (p=0.012), 1.0 and 15.7 (p<0.001). VF1 and VF2 (63% and 53%) were not significantly affected. The corresponding figures of CHX were 0.42, 0.43, 6.77, 33 and 16%, which were all significantly lower (all p<0.001). On comparing the two chlorhexidine solutions, CHX showed significantly higher reductions of all parameters.

Conclusion: The results suggest that the 0.2% alcohol‐containing solution showed superiority in inhibiting plaque re‐growth and reducing bacterial vitality compared with the solution with ADS.
The Alkaline Comet Assay: Towards Validation in Biomonitoring of DNA Damaging Exposures
Authors: Møller Peter
Published: April 2006

Abstract: Generation of DNA damage is considered to be an important initial event in carcinogenesis. The single cell gel electrophoresis (comet) assay is a technically simple and fast method that detects genotoxicity in virtually any mammalian cell type without requirement for cell culture. This review discusses the strength of the comet assay in biomonitoring at its present state of validation. The simple version of the alkaline comet assay detects DNA migration caused by strand breaks, alkaline labile sites, and transient repair sites. By incubation with bacterial glycosylase/endonuclease enzymes, broad classes of oxidative DNA damage, alkylations, and ultraviolet light‐induced photoproducts are detected as additional DNA migration. The most widely measured enzyme sensitive sites have been those detected by formamidopyrimidine DNA glycosylase (FPG) and endonuclease III (ENDOIII). Reports from biomonitoring studies show that the basal level of DNA damage in leukocytes is influenced be a variety of lifestyle and environmental exposures, including exercise, air pollution, sunlight, and diet. Although not all types of carcinogenic exposures should be expected to damage DNA in leukocytes, the comet assay is a valuable method for detection of genotoxic exposure in humans. However, the predictive value of the comet assay is unknown because it has not been investigated in prospective cohort studies. Also, it is important that the performance of the assay is investigated in multi‐laboratory validation trials. As a tool in risk assessment the comet assay can be used in characterization of hazards.
The Prevalence of Suspected and Challenge‐Verified Penicillin Allergy in a University Hospital Population
Authors: Borch Jakob E. , Andersen Klaus E. , Bindslev‐Jensen C.
Published: April 2006

Abstract: Suspected penicillin allergy is common among hospitalised patients, but the quality of the information given by the patient is often doubtful. Alleged penicillin allergics are likely to be treated with more toxic, broad‐spectered, and more expensive antibiotics, with effects on microbial resistance patterns and public economy as a consequence. We performed a cross‐sectional case‐control study with two visits to all clinical departments of a large university hospital in order to find in‐patients with medical files labelled “penicillin allergy” or who reported penicillin allergy upon admission. Patient histories were obtained via a questionnaire, and they were offered investigation for penicillin allergy with specific IgE, basophil histamine release, skin prick tests, intradermal tests and drug challenge tests. Finally, the pharmaco‐economical consequences of the penicillin allergy were estimated. In a cohort of 3642 patients, 96 fulfilled the inclusion criteria giving a point‐prevalence of alleged penicillin allergy of 5% in a hospital in‐patient population. Mean time elapsed since the alleged first reaction to penicillin was 20 years. The skin was the most frequently affected organ (82.2%), maculo‐papular exanthema (35.4%) and urticaria (10.4%) being the most frequently reported reactions. 25% did not recall the time of their reaction. 82.2% did not remember the name of the penicillin they reacted to. 34.8% had been treated with penicillins after suspicion of penicillin allergy had been raised. None of these reacted to penicillins. 33.3% of the patients receiving antibiotics during their current hospitalisation were prescribed penicillins. 2% developed non‐severe exanthema. The average acquisition costs for antibiotics to penicillin allergic patients were € 278, compared to € 119 had they been non‐allergics. The prevalence of suspected penicillin allergy was lower than reported elsewhere. A substantial number of patients failed to recall basic information about their alleged allergy. Patients reporting penicillin allergy upon admission and labels stating penicillin allergy on medical files are ignored in almost a third of patients receiving antibiotics. The acquisition costs for antibiotics to penicillin allergic patients were higher, compared to the cost had the patients been non‐allergics.
Rewarding Properties of 1‐Benzylpiperazine, a New Drug of Abuse, in Rats
Authors: Meririnne Esa , Kajos Miina , Kankaanpää Aino , Seppälä Timo
Published: April 2006

Abstract: 1‐Benzylpiperazine (also known as ‘Legal X’, ‘Legal E’, or ‘A2’) is a psychoactive compound increasingly encountered on the clandestine market. Previous experimental data suggest that the compound possesses addictive properties. In the present study, we used the conditioned place preference method in the rat to test whether 1‐benzylpiperazine possesses rewarding properties. Furthermore, the mechanisms of the 1‐benzylpiperazine reward were investigated using selected dopamine and serotonin receptor antagonists. 1‐Benzylpiperazine (1.25, 5, and 20 mg/kg) induced dose‐dependently place preference. This place preference was attenuated by the antagonists SCH23390 (0.2 mg/kg; dopamine D1‐like receptors) and MDL72222 (1.0 mg/kg; serotonin3 receptors), but not by raclopride (0.8 mg/kg; dopamine D2‐like receptors) or ketanserin (2 mg/kg; preferentially serotonin2 receptors). Our results show that 1‐benzylpiperazine possesses rewarding properties in the rat, which suggests the compound to be susceptible to human abuse. The brain dopaminergic and serotonergic systems appear to be involved in the 1‐benzylpiperazine reward.
Treatment of Experimental Chronic Chagas Disease with Trifluralin
Authors: Zaidenberg Anibal , Luong Tai , Lirussi Darío , Bleiz Jorge , Buono María Beatriz Del , Quijano Graciela , Drut Ricardo , Kozubsky Leonora , Marron Adriana , Buschiazzo Héctor
Published: April 2006

Abstract: We tested trifluralin against Trypanosoma cruzi in a model of chronic Chagas disease in mice. CF1 mice (n=148) were intraperitoneally infected with 105 trypomastigotes of T. cruzi, H510C8C3 clone. One hundred mice were partially treated with benznidazole. Mortality was 100% at day 41 in the control group (n=48). At day 90 of the chronic disease (74% survival) mice were divided into three groups and treated orally with trifluralin (50 mg/kg/day, n=26), benznidazole (50 mg/kg/day, n=25) and vehicle (peanut oil; control group, n=23) for 60 days. Electrocardiography (under pentobarbital anaesthesia, 30 mg/kg/dose), serologic immunofluorescence and microstrout were performed at the beginning and at the end of the treatment. Mice were sacrificed at day 10 after treatment; cardiac tissue was studied histopathologically and polymerase chain reaction (PCR) was performed. Spontaneous mortality was 30.43%, 3.85% and 4% in the control, trifluralin and benznidazole groups, respectively (significant survival, P=0.03). Microstrouts were negative in all three groups. Negative immunofluorescence titers were 0%, 16% (P=0.05) and 29% (P<0.02) in the control, trifluralin and benznidazole groups, respectively. The prevailing electrocardiographic disorder was prolongation of the PR interval in the control group, which was not significantly altered in trifluralin‐ and benznidazole‐treated mice, suggesting that trifluralin and benznidazole improve or even stop the damage caused by the disease on the conduction system. Trifluralin‐ and benznidazole‐treated animals showed similar histologic patterns of myocarditis. PCR results were negative for benznidazole and trifluralin (100% and 70.8%, respectively). These results show the therapeutic potential of trifluralin in the treatment of chronic Chagas disease.
Choline‐Modulated Arsenic Trioxide‐Induced Prolongation of Cardiac Repolarization in Guinea Pig
Authors: Sun Hong‐Li , Chu Wen‐Feng , Dong De‐Li , Liu Yan , Bai Yun‐Long , Wang Xiao‐Hui , Zhou Jin , Yang Bao‐Feng
Published: April 2006

Abstract: Arsenic trioxide (As2O3) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As2O3‐induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As2O3‐caused QT prolongation in guinea pig. Intravenous administration of As2O3 prolonged the QT interval in a dose‐ and time‐dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole‐cell patch clamp technique and confocal laser scanning microscopy, we found that As2O3 significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L‐type calcium currents (ICa‐L), inhibited delayed rectifier potassium currents (IK), and increased intracellular calcium concentration ([Ca2+]i) in guinea pig ventricular myocytes. Choline corrected As2O3‐mediated alterations of action potential duration, ICa‐L and [Ca2+]i, but had no effect on the IK inhibition. As2O3 markedly disturbed the normal equilibrium of transmembrane currents (increasing ICa‐L and suppressing IK) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated ICa‐L and [Ca2+]i in ventricular myocytes during As2O3 application.
Neonatal Jaundice and Bilirubin UDP‐Glucuronosyl Transferase 1A1 Gene Polymorphism in Turkish Patients
Authors: Babaoglu Melih O. , Yigit Sule , Aynacioglu A. Sukru , Kerb Reinhold , Yurdakok Murat , Bozkurt Atila
Published: April 2006

Abstract: Bilirubin uridine diphosphate‐glucuronosyltransferase (B‐UGT) is the rate‐limiting enzyme for the conjugation of bilirubin with glucuronic acid in its excretion process into the bile. Variations in B‐UGT gene (UGT‐1A1) have been related to disorders characterised by hyperbilirubinaemia. The aim of this study was to investigate whether the number of thymine‐adenine repeats in the promoter region of UGT‐1A1 was related to non‐physiologic hyperbilirubinemia of unexplained aetiology in Turkish newborns. These patients (n=106) were genotyped for their thymine‐adenine repeat number in the promoter region of UGT‐1A1, and were divided into two groups according to their bilirubin level. Forty‐nine newborns with bilirubin levels higher than 17 mg/dl within the first ten days of life comprised the hyperbilirubinaemia group and 25 newborns with bilirubin levels higher than 10 mg/dl after fifteen days of life formed the prolonged jaundice group. Thirty‐two newborns were included as healthy controls. The observed frequencies for the wild‐type six repeat allele thymine‐adenine (TA6) within each subject group were similar (P>0.05; 75.5%, 78.0% and 73.4%, respectively). Likewise, the distribution of TA6/6, TA6/7 and TA7/7 genotypes among three groups were similar. These results imply that the TA7 repeat allele of UGT1A1 (UGT1A1*28) is a common variant in the Turkish population. Our results do not suggest an association between thymine‐adenine repeat polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or prolonged jaundice in Turkish neonates.
Best‐practice algorithms for the use of a bilayered living cell therapy (Apligraf®) in the treatment of lower‐extremity ulcers
Authors: Cavorsi Joseph , Vicari Frank , Wirthlin Douglas J. , Ennis William , Kirsner Robert , O'Connell Sean M. , Steinberg John , Falanga Vincent
Published: April 2006

Tissue‐engineered skin substitutes such as Apligraf® have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard‐to‐heal wounds since 1998, Apligraf® has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound‐healing technologies, such as tissue‐engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf®, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf® treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user‐friendly direction simplifying both patient selection and appropriate use of Apligraf® within the context of good wound‐healing practice.
Assessment of health‐related quality of life in patients with lymphedema of the lower limb
Authors: Franks Peter J. , Moffatt Christine J. , Doherty Debra C. , Williams Anne F. , Jeffs Eunice , Mortimer Peter S.
Published: April 2006

The purpose of this study was to examine the use of a number of tools in the evaluation of health‐related quality of life in patients with lower limb lymphedema, and to determine the consequences of cancer history and concurrent leg ulceration. Patients in one health trust having lower limb lymphedema were identified and interviewed at entry and after 24 weeks. The short form‐36 (SF‐36), modified Barthel scale, McGill short form pain questionnaire, and Euroqol were administered at both time points. Of the 164 (median age=76.9 years, 70.7% women) patients who comprised the study population, 15.2% had a history of cancer and 30.4% had coexisting current leg ulceration. Internal consistencies were high for all scales (Cronbach's α >0.80). There were high ceiling effects for a number of SF‐36 scores, and high floor effects in these and the McGill short form pain questionaire, scales. Despite these limitations, there was strong evidence that treatment led to significant improvements in six of eight scores of the SF‐36, three of three scores of the McGill short form pain questionnaire and the modified Barthel scale (all p<0.05). The improvement in physical functioning was significantly greater for patients who entered the study with a leg ulcer (mean different=9.1, 95% confidence interval 2.1–16.1, p=0.011). Patients treated with compression bandaging had significantly greater improvements for physical functioning (10.2) than those treated with compression hoisery (−1.5) or no treatment (−2.0), p=0.001. Of the tools assessed, the SF‐36, appears to be the most appropriate for use in this patient group.
Low serum zinc level as a predictive factor of delayed wound healing in total hip replacement
Authors: Zorrilla Pedro , Gómez Luis A. , Salido José A. , Silva Agustín , López‐Alonso Antonio
Published: April 2006

Delayed wound healing after total arthroplasty puts the patient at risk for superficial and deep infection, with substantial economic and social consequences. The objective of this study was to assess serum zinc levels as a tool for predicting such a delay in patients with primary osteoarthritis or osteoarthritis secondary to avascular necrosis. We conducted a prospective study of 80 total hip arthroplasties, analyzing possible correlations between delayed healing and serum zinc, nutritional parameters, and other demographic and epidemiological variables. The predictive value of preoperative serum zinc levels and lymphocyte counts was confirmed; thus, an arthroplasty procedure could be timed to minimize risk.
Inhibition of procollagen C‐proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring
Authors: Reid Russell R. , Mogford Jon E. , Butt Richard , DeGiorgio‐Miller Alex , Mustoe Thomas A.
Published: April 2006

Hypertrophic scarring, which results from excessive collagen deposition at sites of dermal wound repair, can be functionally and cosmetically debilitating to the surgical patient. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. One of the key steps in collagen stabilization is the cleavage of the C‐terminal propeptide from the precursor molecule to form collagen fibrils, a reaction catalyzed by procollagen C‐proteinase (PCP). We tested the ability of a PCP inhibitor to reduce hypertrophic scar formation in a rabbit ear model. After the placement of four, 7‐mm dermal wounds on each ear, New Zealand white rabbits received PCP inhibitor subcutaneously in the left ear at four time points postwounding: days 7, 9, 11, 13 (early treatment; n=20 wounds) or days 11, 13, 15, 17 (late treatment; n=20 wounds). The right ear of each animal served as a control (vehicle alone). Wounds were harvested on postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. Early treatment of wounds with PCP inhibitor did not reduce scar formation compared with controls (p>0.05). However, late treatment resulted in a statistically significant reduction in the scar elevation index (p<0.01). Our results point not only to the potential use of PCP inhibitors to mitigate hypertrophic scarring but also to the temporal importance of drug delivery for antiscarring therapy.
Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice
Authors: Braun Michael , Lelieur Karin , Kietzmann Manfred
Published: April 2006

As membrane‐bound receptors for adenosine, purines, and pyrimidines, purinoceptors are expressed in nearly all cell types throughout the mammalian organism. Previous studies showed that purinoceptors are involved in the regulation of proliferation and differentiation of most target cells. The present study was performed to elucidate their role in keratinocyte proliferation and wound healing. The expression of the mRNA of several adenosine and P2Y receptors was shown in the immortalized murine keratinocyte cell line MSC‐P5 and primary cultured keratinocytes of four different mouse strains. The nonselective adenosine receptor agonist 5′‐(N‐ethyl)‐carboxamidoadenosine enhanced the growth of MSC‐P5 cells in vitro via the A2Breceptor. The proliferative stimulus of adenosine triphosphate and uridine triphosphate on this cell line was mediated by the P2Y2receptor. The mitogenic effect of the purinergic substances was inhibited by simultaneous treatment with respective antagonists. Studies in a mouse model of dexamethasone‐induced impaired wound healing showed the in vivo efficacy of the purinoceptor agonists. These studies confirm that pharmacological actions via purinoceptors offer an intriguing possibility in the treatment of impaired wound healing. Nevertheless, further investigations are needed to elucidate fully the role of purinergic mechanisms involved in wound healing.
Expression and possible mechanism of c‐ski, a novel tissue repair‐related gene during normal and radiation‐impaired wound healing
Authors: Liu Xia , Zhang En , Li Ping , Liu Jianzhong , Zhou Ping , Gu Da‐yong , Chen Xingyun , Cheng Tianmin , Zhou Yuanguo
Published: April 2006

C‐ski is a complicated regulating factor for fibroblast proliferation and an important co‐repressor of Smad3. Although inhibiting Smad3 activity can markedly promote wound healing because Smad3 mediates the role of transforming growth factor‐β in inhibiting cell proliferation and inducing cell apoptosis; there has been no report on whether c‐ski is expressed during wound healing and the relationship between its expression and wound healing. By establishing animal models of normal and radiation‐impaired wound healing and using immunohistochemistry, in situ hybridization, and reverse transcription‐polymerase chain reaction, we found that c‐ski was expressed after wounding and reached its peak on day 9 and then significantly decreased. C‐ski was present in all repair cells, and was especially prominent in fibroblasts. Compared with the control side, the irradiated side showed a lower expression of c‐ski on postwound days 3–9, but higher on day 15, and not significantly different after the wound was healed. The expression of Smad3 was in contrast to the c‐ski and cellular proliferation was similar to that of c‐ski expression. The apoptosis index was significantly higher on the irradiated side on days 3–9 compared with the control side. In vitro, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide results showed that c‐ski could reverse the inhibitory role of Smad3 on fibroblast proliferation. Flow cytometry analysis found that c‐ski also diminished fibroblast apoptosis induced by Smad3 transfection. These results suggest that there is not only obvious expression of this regulatory protein but there is also a significant change in the levels of c‐ski during wound healing. Its in vivo expression pattern and experiments in vitro suggest that c‐ski may be involved in tissue repair by repressing Smad3 activity. Radiation can reduce c‐ski and increase Smad3 expression, resulting in elevated Smad3 activity, resulting in diminished cell proliferation, cell apoptosis, and wound‐healing delays.
Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression
Authors: Shannon Diane B. , McKeown Scott T.W. , Lundy Fionnuala T. , Irwin Chris R.
Published: April 2006

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, α‐smooth muscle actin expression (α‐SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor ‐β1 and ‐β3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7‐day period. α‐SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme‐linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of α‐SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor‐β1 and ‐β3, over the concentration range of 0.1–10 ng/mL, had similar effects on cell function, stimulating both gel contraction and α‐SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.
Serum‐dependent effects on adult and fetal tendon fibroblast migration and collagen expression
Authors: Brink Hallie E. , Miller Gregory J. , Beredjiklian Pedro K. , Nicoll Steven B.
Published: April 2006

Cell migration and extracellular matrix synthesis play an important role in the wound‐healing response to injury. Several studies have described differences in migratory behavior and collagen biosynthetic activity in adult vs. fetal skin fibroblasts. The objective of this study was to examine the serum‐ and age‐dependent effects on cell migration and collagen expression in tendon fibroblasts. Medial tendon fibroblasts were isolated from pregnant ewes and their fetuses, and cultured with and without serum for up to 7 days. Cell migration was determined by quantitative image analysis, and collagen expression was assessed by reverse transcription‐polymerase chain reaction and immunohistochemical staining. In serum‐containing medium, tendon fibroblasts migrated significantly faster than cells in serum‐free medium. Additionally, fetal tendon fibroblasts migrated significantly faster than adult tendon fibroblasts under both culture conditions. The expression of types I and III collagen mRNA was significantly up‐regulated in tendon cell populations in serum‐free medium compared with those in serum‐containing medium. Quantitative assessment of collagen staining indicated that fetal tenocytes produced more type I collagen than adult tenocytes under both culture conditions. These findings suggest that there is an inherent difference between adult and fetal tendon fibroblasts, which may have implications in the wound‐healing response in tendons.
Higher skeletal muscle α2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise
Authors: Roepstorff Carsten , Thiele Maja , Hillig Thore , Pilegaard Henriette , Richter Erik A. , Wojtaszewski Jørgen F. P. , Kiens Bente
Published: April 2006

5′AMP‐activated protein kinase (AMPK) is an energy sensor activated by perturbed cellular energy status such as during muscle contraction. Activated AMPK is thought to regulate several key metabolic pathways. We used sex comparison to investigate whether AMPK signalling in skeletal muscle regulates fat oxidation during exercise. Moderately trained women and men completed 90 min bicycle exercise at 60%. Both AMPK Thr172 phosphorylation and α2AMPK activity were increased by exercise in men (∼200%, P < 0.001) but not significantly in women. The sex difference in muscle AMPK activation with exercise was accompanied by an increase in muscle free AMP (∼164%, P < 0.01), free AMP/ATP ratio (159%, P < 0.05), and creatine (∼42%, P < 0.001) in men but not in women (NS), suggesting that lack of AMPK activation in women was due to better maintenance of muscle cellular energy balance compared with men. During exercise, fat oxidation per kg lean body mass was higher in women than in men (P < 0.05). Regression analysis revealed that a higher proportion of type 1 muscle fibres (∼23%, P < 0.01) and a higher capillarization (∼23%, P < 0.05) in women than in men could partly explain the sex difference in α2AMPK activity (r=−0.54, P < 0.05) and fat oxidation (r= 0.64, P < 0.05) during exercise. On the other hand, fat oxidation appeared not to be regulated via AMPK. In conclusion, during prolonged submaximal exercise at 60%, higher fat oxidation in women cannot be explained by higher AMPK signalling but is accompanied by improved muscle cellular energy balance in women probably due to sex specific muscle morphology.
Polar PIN Localization Directs Auxin Flow in Plants
Authors: Wiśniewska Justyna , Xu Jian , Seifertová Daniela , Brewer Philip B. , Růžička Kamil , Blilou Ikram , Rouquié David , Benková Eva , Scheres Ben , Friml Jiří
Published: April 2006

Polar flow of the phytohormone auxin requires plasma membrane‐associated PIN proteins and underlies multiple developmental processes in plants. Here we address the importance of the polarity of subcellular PIN localization for the directionality of auxin transport in Arabidopsis thaliana. Expression of different PINs in the root epidermis revealed the importance of PIN polar positions for directional auxin flow and root gravitropic growth. Interfering with sequence-embedded polarity signals directly demonstrates that PIN polarity is a primary factor in determining the direction of auxin flow in meristematic tissues. This finding provides a crucial piece in the puzzle of how auxin flow can be redirected via rapid changes in PIN polarity.
PIN Proteins Perform a Rate-Limiting Function in Cellular Auxin Efflux
Authors: Petrášek Jan , Mravec Jozef , Bouchard Rodolphe , Blakeslee Joshua J. , Abas Melinda , Seifertová Daniela , Wiśniewska Justyna , Tadele Zerihun , Kubeš Martin , Čovanová Milada , Dhonukshe Pankaj , Skůpa Petr , Benková Eva , Perry Lucie , Křeček Pavel , Lee Ok Ran , Fink Gerald R. , Geisler Markus , Murphy Angus S. , Luschnig Christian , Zažímalová Eva , Friml Jiří
Published: April 2006

Intercellular flow of the phytohormone auxin underpins multiple developmental processes in plants. Plant-specific pin-formed (PIN) proteins and several phosphoglycoprotein (PGP) transporters are crucial factors in auxin transport–related development, yet the molecular function of PINs remains unknown. Here, we show that PINs mediate auxin efflux from mammalian and yeast cells without needing additional plant-specific factors. Conditional gain-of-function alleles and quantitative measurements of auxin accumulation in
Arabidopsis
and tobacco cultured cells revealed that the action of PINs in auxin efflux is distinct from PGP, rate-limiting, specific to auxins, and sensitive to auxin transport inhibitors. This suggests a direct involvement of PINs in catalyzing cellular auxin efflux.
Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A
Authors: Huang Ying , Fang Jia , Bedford Mark T. , Zhang Yi , Xu Rui-Ming
Published: April 2006

Biological responses to histone methylation critically depend on the faithful readout and transduction of the methyl-lysine signal by “effector” proteins, yet our understanding of methyl-lysine recognition has so far been limited to the study of histone binding by chromodomain and WD40-repeat proteins. The double tudor domain of JMJD2A, a Jmjc domain–containing histone demethylase, binds methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an interdigitated structure, and the unusual fold is required for its ability to bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound in a cage of three aromatic residues, two of which are from the tudor-2 motif, whereas the binding specificity is determined by side-chain interactions involving amino acids from the tudor-1 motif. Our study provides mechanistic insights into recognition of methylated histone tails by tudor domains and reveals the structural intricacy of methyl-lysine recognition by two closely spaced effector domains.
Evaluation of Multiplex Flow Cytometric Opsonophagocytic Assays for Determination of Functional Anticapsular Antibodies to
Streptococcus pneumoniae
Authors: Martinez Joseph E. , Clutterbuck Elizabeth A. , Li Han , Romero-Steiner Sandra , Carlone George M.
Published: April 2006

The determination of functional antipneumococcal capsular polysaccharide antibodies by sequential testing of pre- and postvaccination serum samples one serotype at a time is sample-intensive and time-consuming and has a relatively low throughput. We tested several opsonophagocytic assay (OPA) formats, including the reference killing method, a monovalent bacterium-based flow method, a trivalent bacterium-based flow method, and a tetravalent bead-based flow method using a panel of sera (4 prevaccination and 16 postvaccination, from healthy adults immunized with the 23-valent pneumococcal polysaccharide vaccine). The trivalent and tetravalent methods allow simultaneous measurements of opsonic antibodies to multiple pneumococcal serotypes. The trivalent bacterial-flow OPA had significant correlation to the reference OPA method and to a previously published flow cytometric OPA (
r
values ranged from 0.61 to 0.91,
P
< 0.05) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The tetravalent OPA had significant correlation to all OPA method formats tested (
r
values from 0.68 to 0.92,
P
< 0.05) for all seven serotypes tested. This tetravalent OPA is an alternative to other OPA methods for use during vaccine evaluation and clinical trials. Further, the flow cytometric multiplex OPA format has the potential for expansion beyond the current four serotypes to eight or more serotypes, which would further increase relative sample throughput while reducing reagent and sample volumes used.