Biliary atresia: Swiss national study, 1994-2004.

OBJECTIVES: To determine the epidemiology of biliary atresia (BA) in Switzerland, the outcome of the children from diagnosis, and the prognostic factors. PATIENTS AND METHODS: The records of all patients with BA born in Switzerland between January 1994 and December 2004 were analyzed. Survival rates were calculated with the Kaplan-Meier method, and prognostic factors evaluated with the log rank test. Median follow up was 58 months (range, 5-124). RESULTS: BA was diagnosed in 48 children. Incidence was 1 in 17,800 live births (95% confidence interval 1/13,900-1/24,800), without significant regional, annual, or seasonal variation. Forty-three children underwent a Kasai portoenterostomy (PE) in 5 different Swiss pediatric surgery units. Median age at Kasai PE was 68 days (range, 30-126). Four-year survival with native liver after Kasai PE was 37.4%. Liver transplantation (LT) was needed in 31 in 48 children with BA, including 5 patients without previous Kasai PE. Four patients (8%, all born before 2001) died while waiting for LT, and 29 LT were performed in 27 patients (28 in Geneva and 1 in Paris). All of the transplanted patients are alive. Four-year overall BA patient survival was 91.7%. Four-year survival with native liver was 75% in patients who underwent Kasai PE before 46 days, 33% in patients operated on between 46 and 75 days, and 11% in patients operated on after 75 days (P = 0.02). CONCLUSIONS: Overall survival of patients with BA in Switzerland compares favorably with current international standards, whereas results of the Kasai operation could be improved to reduce the need for LTs in infancy and early childhood.

Is Less Chemotherapy Detrimental in Adults with Philadelphia Chromosome (Ph)-Positive Acute Lymphoblastic Leukemia (ALL) Treated with High-Dose Imatinib? Results of the Prospective Randomized Graaph-2005 Study

Aim: To compare a less intensive regimen based on high-dose imatinib (IM) to an intensive IM/HyperCVAD regimen in adults with Ph+ ALL, in terms of early response and outcome after stem cell transplantation (SCT). Methods: Patients aged 18-60 years with previously untreated Ph+ ALL not evolving from chronic myeloid leukemia were eligible if no contra-indication to chemotherapy and SCT (ClinicalTrials.gov ID, NCT00327678). After a steroid prephase allowing Ph and/or BCR-ABL diagnosis, cycle 1 differed between randomization arms. In arm A (IM-based), IM was given at 800 mg on day 1-28, combined with vincristine (2 mg, day 1, 8, 15, 22) and dexamethasone (40 mg, day 1-2, 8-9, 15-16, and 22-23) only. In arm B (IM/HyperCVAD), IM was given at 800 mg on day 1-14, combined with adriamycin (50 mg/m2, day 4), cyclophosphamide (300 mg/m2/12h, day 1, 2, 3), vincristine (2 mg, day 4 and 11), and dexamethasone (40 mg, day 1-4 and 11-14). All patients received a cycle 2 combining high-dose methotrexate (1 g/m2, day 1) and AraC (3 g/m2/12h, day 2 and 3) with IM at 800 mg on day 1-14, whatever their response. Four intrathecal infusions were given during this induction/consolidation period. Minimal residual disease (MRD) was centrally evaluated by quantitative RQ-PCR after cycle 1 (MRD1) and cycle 2 (MRD2). Major MRD response was defined as BCR-ABL/ABL ratio <0.1%. Then, all patients were to receive allogeneic SCT using related or unrelated matched donor stem cells or autologous SCT if no donor and a major MRD2 response. IM/chemotherapy maintenance was planned after autologous SCT. In the absence of SCT, patients received alternating cycles 1 (as in arm B) and cycles 2 followed by maintenance, like in the published IM/HyperCVAD regimen. The primary objective was non-inferiority of arm A in term of major MRD2 response. Secondary objectives were CR rate, SCT rate, treatment- and transplant-related mortality, relapse-free (RFS), event-free (EFS) and overall (OS) survival. Results: Among the 270 patients randomized between May 2006 and August 2011, 265 patients were evaluable for this analysis (133 arm A, 132 arm B; median age, 47 years; median follow-up, 40 months). Main patient characteristics were well-balanced between both arms. Due to higher induction mortality in arm B (9 versus 1 deaths; P=0.01), CR rate was higher in the less intensive arm A (98% versus 89% after cycle 1 and 98% versus 91% after cycle 2; P= 0.003 and 0.006, respectively). A total of 213 and 205 patients were evaluated for bone marrow MRD1 and MRD2. The rates of patients reaching major MRD response and undetectable MRD were 45% (44% arm A, 46% arm B; P=0.79) and 10% (in both arms) at MRD1 and 66% (68% arm A, 63.5% arm B; P=0.56) and 25% (28% arm A, 22% arm B; P=0.33) at MRD2, respectively. The non-inferiority primary endpoint was thus demonstrated (P= 0.002). Overall, EFS was estimated at 42% (95% CI, 35-49) and OS at 51% (95% CI, 44-57) at 3 years, with no difference between arm A and B (46% versus 38% and 53% versus 49%; P=0.25 and 0.61, respectively). Of the 251 CR patients, 157 (80 arm A, 77 arm B) and 34 (17 in both arms) received allogeneic and autologous SCT in first CR, respectively. Allogeneic transplant-related mortality was similar in both arms (31.5% versus 22% at 3 years; P=0.51). Of the 157 allografted patients, 133 had MRD2 evaluation and 89 had MRD2 <0.1%. In these patients, MRD2 did not significantly influence post-transplant RFS and OS, either when tested with the 0.1% cutoff or as a continuous log covariate. Of the 34 autografted patients, 31 had MRD2 evaluation and, according to the protocol, 28 had MRD2 <0.1%. When restricting the comparison to patients achieving major MRD2 response and with the current follow-up, a trend for better results was observed after autologous as compared to allogeneic SCT (RFS, 63% versus 49.5% and OS, 69% versus 58% at 3 years; P=0.35 and P=0.08, respectively). Conclusions: In adults, the use of TK inhibitors (TKI) has markedly improved the results of Ph+ ALL therapy, now close to those observed in Ph-negative ALL. We demonstrated here that chemotherapy intensity may be safely reduced when associated with high-dose IM. We will further explore this TKI-based strategy using nilotinib prior to SCT in our next GRAAPH-2013 trial. The trend towards a better outcome after autologous compared to allogeneic SCT observed in MRD responders validates MRD as an important early surrogate endpoint for treatment stratification and new drug investigation in this disease.

Business Sphere, Vol. 18, no.2

The biosciences industry significantly impacts Iowa’s economy. Kemin, Integrated DNA Technologies, Archer Daniels Midland Co., Roquette America, Cargill, Monsanto and DuPont’s Pioneer Hi-Bred International are only a few of Iowa’s 1,800 bioscience companies employing more than 83,000 people. Everyday, Kemin and other Iowa life sciences companies seek to commercialize new bioscience innovations. Together with Iowa’s outstanding business climate, a skilled, well educated and adaptable workforce, and an enviable quality of life, Iowa is providing bioscience companies with an exciting new resource to assist us in our endeavors: The Biosciences Alliance of Iowa.

Business Sphere, Vol. 21, no.4

Iowans have long been proud of our educational heritage. With I-VREP, business and educational leaders are taking steps to enhance its world-class education for Iowans, while ensuring the qualified workforce needed by Iowa’s businesses competing in a global economy. For more information on the Iowa Virtual Reality Education Pathfinder, or a confidential consultation on how Iowa innovation can fuel your company’s growth, contact IDED at 800.245.IOWA or visit iowalifechanging.com

Business Sphere, Vol. 20, no.1

Wind power is the fastest growing source of energy in the nation. New installations have expanded total U.S. generating capacity by 45 percent and injected over $9 billion in new investments into the economy in 2007. These new wind projects accounted for about 30 percent of the entire new power-producing capacity added nationally in 2007. According to our figures at the American Wind Energy Association, installed wind power capacity in the U.S. is now over 16,800 megawatts, and the future looks bright. With every wind turbine that goes up, America’s dependence on fossil fuels for power generation goes down. Wind energy represents a tremendous opportunity to use a non-polluting, inexhaustible source to meet our electric power needs.

K-T transition in Deccan Traps of central India marks major marine Seaway across India

Deccan intertrappean sediments in central India are generally considered as terrestrial deposits of Maastrichtian age, but the Cretaceous-Tertiary (K-T) position is still unknown. Here we report the discovery of the K-T transition, a marine incursion and environmental changes preserved within the intertrappean sediments at Jhilmili, Chhindwara District, Madhya Pradesh. Integrative biostratigraphic, sedimentologic, mineralogic and chemostratigraphic analyses reveal the basal Danian in the intertrappean sediments between lower and upper trap basalts that regionally correspond to C29r and the C29R/C29N transition, respectively. Intertrappean deposition occurred in predominantly terrestrial semi-humid to and environments. But a short aquatic interval of fresh water ponds and lakes followed by shallow coastal marine conditions with brackish marine ostracods and early Danian zone P1a planktic foraminifera mark this interval very close to the K-T boundary. This marine incursion marks the existence of a nearby seaway, probably extending inland from the west through the Narmada and Tapti rift valleys. The Jhilmili results thus identify the K-T boundary near the end of the main phase of Deccan eruptions and indicate that a major seaway extended at least 800 km across India. (C) 2009 Elsevier B.V. All rights reserved.

Capacidade de adsorção de fósforo em solos de várzea do Estado do Rio Grande do Sul

Os solos de várzea, sazonalmente alagados para o cultivo do arroz, apresentam alternância nas condições de oxidação e redução, a qual determina modificações intensas na fase sólida mineral do solo e na dinâmica de elementos altamente reativos, como o P. Assim, formas de óxidos e hidróxidos de Fe de baixa cristalinidade tornam-se predominantes com o passar do tempo e poderão ser os componentes mais importantes na adsorção de P durante o período em que o solo permanece drenado; além disso, elas controlariam a liberação de P provocada pelo posterior alagamento para cultivo do arroz. Os objetivos do presente trabalho foram avaliar a capacidade máxima de adsorção de P (CMAP) de amostras de 16 solos de várzea do Estado do Rio Grande do Sul (RS) e buscar características químicas ou físicas de solo que melhor se correlacionam com a CMAP. Foram coletadas 16 amostras da camada de 0 a 20 cm de solos de várzea, com ampla faixa de variação de características químicas e físicas. Logo em seguida, elas foram secas ao ar, moídas e peneiradas a 2 mm. A determinação da CMAP foi feita por meio do ajuste de isotermas de adsorção, em que subamostras foram colocadas em contato com concentrações crescentes de P (0, 50, 100, 200, 300, 600, 900 e 1.800 mg kg-1 de P no solo) durante 16 h. Após esse período, determinou-se o P em equilíbrio na solução, sendo a equação de Langmuir ajustada aos dados. Houve grande diversidade na CMAP entre os solos (71 a 933 mg kg-1 de P no solo), a qual foi correlacionada significativamente com os teores de argila, matéria orgânica e óxidos de Fe extraído por ditionito e oxalato de amônio. A diferente CMAP se refletiu na quantidade de P necessária para alterar o P disponível dos solos estimado pelo método Mehlich-1.

Recomendação de adubação nitrogenada para trigo em sucessão ao silho e soja sob sistema plantio direto no Paraguai

O nitrogênio (N) é um dos nutrientes mais requeridos pelo trigo e, muitas vezes, não é suprido nem na quantidade nem na época ideal. Devido à importância da adubação nitrogenada no trigo e à carência de informações disponíveis no Paraguai, foi desenvolvido este trabalho com o objetivo de propor uma recomendação nitrogenada para trigo sob sistema plantio direto. Cinco experimentos em rede foram realizados a campo, durante dois anos, em três departamentos do Paraguai, abrangendo os principais solos (Oxisols, Inceptisols e Ultisols) e regiões produtoras (Alto Paraná, Itapúa e Missiones). Os tratamentos utilizados no trigo (Triticum aestivum) foram cinco doses de N (0, 30, 60, 90 e 120 kg ha-1) após o milho (Zea mays) e a soja (Glycine max), sendo também investigado o efeito residual de N aplicado no milho (0, 60, 120, 180 e 240 kg ha-1) na nutrição do trigo, em parcelas de 5 x 8 m, em delineamento de blocos ao acaso com três repetições. O trigo respondeu economicamente, em média, à dose de 35 kg ha-1 de N após a soja para produtividades em torno de 3.100 kg ha-1; após o milho, respondeu economicamente, em média, até 30 kg ha-1 de N, atingindo produtividade de 2.100 kg ha-1. No solo com teor de matéria orgânica maior que 4 %, verificou-se capacidade de suprir, sem adubação nitrogenada mineral, quantidade suficiente de N para alcançar produtividades de até 2.500 kg ha-1. O trigo respondeu à adubação residual de N aplicado no milho, elevando a produtividade de 1.800 (0 kg ha-1) para 2.300 kg ha-1 (com a dose estimada de 213 kg ha-1 de N aplicado no milho, na média de todos os locais).

Topical therapy is underused in patients with ulcerative colitis.

The availability of new topical preparations for the treatment of left sided ulcerative colitis offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in left-sided colitis as compared to a systemic therapy. Therefore, we were interested in the use of topical therapy in patients with ulcerative colitis. The key question was whether topical treatment is more frequently used than oral therapy in patients with proctitis and left sided colitis. Data of 800 patients of the Swiss IBD cohort study were analyzed. Sixteen percent of patients of the cohort had proctitis, 21% proctosigmoiditis and 41% pancolitis. Topical therapy with 5-ASA or corticosteroids was given in 26% of patients with proctitis, a combined systemic and topical treatment was given in 13%, whereas systemic treatment with 5-ASA without topical treatment was given in 29%. Proportion of topical drug use decreased with respect to disease extension from 39% for proctitis to 13.1% for pancolitis (P=0.001). Patients with severe colitis received a significantly higher dose of topical 5-ASA than patients in remission. Side effects of topical or systemic 5-ASA or budesonide treatment were less frequently seen compared to other medications. Topical treatment was frequently stopped over time. The quality of life was the same in patients with limited disease compared to patients with pancolitis. Topical treatment in proctitis patients was underused in Switzerland. Since topical treatment is safe and effective it should be used to a larger extend.

Acúmulo de nutrientes em frutos de cafeeiro em quatro altitudes de cultivo: cálcio, magnésio e enxofre

As curvas de acúmulo de nutrientes em frutos permitem estimar sua exportação, bem como as épocas de maior demanda. Estudou-se o acúmulo de MS, Ca, Mg e S em frutos de Coffea arabica (L.) da antese à maturação em quatro altitudes, bem como a variação na concentração dos elementos em folhas dos ramos produtivos. O experimento foi constituído da variedade de cafeeiro Catuaí IAC 44 cultivada a 720, 800, 880 e 950 m de altitude, no município de Martins Soares-MG. O delineamento experimental foi inteiramente ao acaso, com três repetições, usando-se um esquema de parcela subdividida no tempo. O aumento da altitude influenciou o ciclo reprodutivo do cafeeiro, pois houve demanda de maior tempo para formação dos frutos. No estádio de expansão rápida, a percentagem de acúmulo de MS, Ca, Mg e S foi maior na altitude de 720 m, comparada, principalmente, à de 950 m. A TMAD (taxa máxima de acúmulo diário) no estádio de granação-maturação apresentou tendência de ser mais tardia com a elevação da altitude. O consumo de nutrientes pelos frutos, assim como o enchimento de grãos, é mais crítico em condições de menor altitude, já que a planta necessita completar esses processos em menor espaço de tempo. De modo geral, na altitude de 720 m ocorreu maior competição fruto/folha pela partição de Ca, Mg e S.

Mobilidade de cátions e correção da acidez de um Cambissolo em função da aplicação superficial de calcário combinado com sais de potássio

A menor reatividade do calcário abaixo dos locais de aplicação deve-se principalmente à sua baixa solubilidade, ao aumento das cargas negativas nas camadas aplicadas devido ao aumento do pH e à pequena permanência dos ânions adicionados na solução do solo. O presente trabalho teve por objetivo avaliar o efeito da adição de ânions a partir de sais de K sobre a superfície do solo, no incremento da reatividade do calcário e na mobilidade de seus cátions em um Cambissolo Húmico. O experimento foi realizado em 2005, em solo com 360 g kg-1 de argila, 60 g kg-1 de matéria orgânica e pH 4,1. Foram utilizadas três doses de calcário dolomítico (0, 0,74 e 1,48 kg m-2), combinadas com 40 g m-2 de K, na forma de KCl ou de KNO3, e com uma testemunha sem K, todos incorporados no primeiro centímetro da coluna do solo. As unidades experimentais (colunas de PVC com 10 x 30 cm, contendo 1,5 kg de solo) foram percoladas 21 vezes, a cada sete dias, com 300 mL de água destilada por semana, totalizando o equivalente a 800 mm de chuva. Os sais potássicos lixiviaram muito mais Ca e Mg do que o calcário. Na média dos três tratamentos de calagem, a adição dos sais aumentou a lixiviação total de Ca, Mg e K, respectivamente de 36 para 132 mg, de 5,8 para 26 mg e de 25 para 51 mg/coluna, relativamente ao tratamento sem adição de sal. Na ausência dos sais, a aplicação da maior dose de calcário dolomítico lixiviou apenas 5 mg de Ca e 1,2 mg/coluna de Mg, em relação ao tratamento sem calcário. A calagem superficial afetou o pH do solo e a concentração de Ca, Mg e Al trocável até a profundidade máxima de 5,0 cm, cujas alterações foram quase sempre proporcionais à dose aplicada, porém não foram influenciadas pela adição dos sais. A aplicação dos fertilizantes potássicos não influenciou a capacidade reativa do calcário aplicado na superfície do solo.

Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate

FSP27 (CIDEC in humans) is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed. However, little is known about its physiological role in liver. Here, we show that fasting regulates liver expression of Fsp27 in a time-dependent manner. Thus, during the initial stages of fasting a maximal induction of 800-fold was achieved, while during the later phase of fasting, Fsp27 expression decreased. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway since: i) CIDEC expression was induced by forskolin, ii) Fsp27 promoter activity was increased by CREB, and iii) Fsp27 expression was upregulated in the liver of Sirt1 knockout animals. Interestingly, pharmacological (etomoxir) or genetic (Hmgcs2 interference) inhibition of the FAO rate increases the in vivo expression of Fsp27 during fasting. Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of auto-regulation between short- and long-term fasting, by which free fatty acids delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, while over longer periods of fasting they are degraded in the mitochondria through the carnitine palmitoyl transferase (CPT) system.

Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function.

We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Comunidades microbianas, atividade enzimática e fungos micorrízicos em solo rizosférico de "Landfarming" de resíduos petroquímicos

As raízes das plantas podem estimular a microbiota do solo, a qual pode contribuir para o aumento da eficiência do processo de remediação. Assim, avaliar a magnitude dos efeitos das raízes sobre a microbiota do solo é de grande interesse e de relevância prática e ecológica. Neste trabalho, avaliaram-se a densidade microbiana, a atividade enzimática, a estrutura da comunidade bacteriana e a presença de fungos micorrízicos arbusculares (FMAs) na rizosfera de plantas de ocorrência espontânea em solo de sistema de "landfarming" de resíduos petroquímicos. Avaliaram-se também solos rizosféricos de cinco plantas e solo-controle sem planta por meio de contagens de microrganismos em placas, eletroforese em gel com gradiente desnaturante (DGGE) de fragmentos do gene rRNA 16S, seqüenciamento genético, atividades enzimáticas, percentagem de colonização radicular e contagem e identificação de esporos de FMAs. As plantas estimularam a densidade microbiana total e da população de degradadores de antraceno, com contagens médias de 1,5 x 10(6) e 2,2 x 10(6) UFC g-1 no solo seco, respectivamente, enquanto, no solo sem planta, essas contagens foram de 5,7 x 10(5) e 2,9 x 10(5) UFC g-1 no solo seco para os respectivos grupos microbianos. As espécies de maior efeito foram Bidens pilosa e Eclipta alba. Entretanto, esses efeitos estimulantes não foram verificados para a atividade enzimática do solo. A colonização micorrízica das raízes (em torno de 40 %) e a densidade de esporos nos solos rizosféricos foram elevadas (entre 900 e 4.800 esporos por 50 cm³ de solo), sendo maior na Brachiaria decumbens. Foram identificadas quatro espécies de FMAs: Acaulospora morrowiae, Glomus intraradices, Paraglomus occultum e Archaeospora trappei. Com exceção de G. intraradices, essas espécies não foram observadas em áreas contaminadas por hidrocarbonetos de petróleo. A análise por DGGE revelou que os solos rizosféricos apresentaram comunidades bacteriana diferente do solo sem plantas. As bactérias degradadoras de antraceno isoladas apresentaram relação filogenética com os gêneros Streptomyces, Nocardioides, Arthrobacter, Pseudoxanthomonas e com gêneros não identificados das famílias Cellulomonadaceae, Xanthomonadaceae e Rhodobacteraceae, sendo quatro destes isolados pertencentes aos actinomicetos. Apenas Nocardioides e o gênero relacionado com a família Cellulomonadaceae foram relatados em áreas brasileiras contaminadas com hidrocarbonetos de petróleo. Conclui-se que as plantas estimulam o aumento da densidade de células bacterianas e alteram a comunidade microbiana do solo de "landfarming" de resíduo petroquímico.

Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.