Fertility clinics have a duty of care towards patients who do not have children with treatment.

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients' hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize 'success' and 'failure' in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop 'plan(s) B', to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.

Effects of tetracycline on entomopathogenic nematodes and their bacterial symbionts.

Among the new contaminants relevant for environment, one of the most significant roles is played by pharmaceuticals like antibiotic products for either human or veterinary use. Their presence could cause serious damage to bacteria and microfauna, like nematodes. Within the widely investigated nematodes, very little is known about the interaction between antibiotics and entomopathogenic nematodes (EPN). EPNs have been used for biological control of crops, due to their ability to penetrate arthropod pests and kill their hosts thanks to a complex symbiotic mechanism with specific gram-negative bacteria. Tetracycline is an antibiotic used in human and veterinary medicine, both for therapeutic purposes and for the growth of livestock. Since its action against gram-negative bacteria is documented, we verified in this study the survival, growth and pathogenicity of two species of EPNs, Steinernema vulcanicum and S. feltiae. All tests were performed with tetracycline in 1% ethanol solution and up to 300 mg/L. Apparently, this incubation did not harm the vitality of EPNs. Both S. vulcanicum as S. feltiae recovered their vitality and entomopathogenic ability after 48 h. Moreover, the latter EPN species did not grow nor reproduce in the hemolymph of the Greater Wax Moth, Galleria mellonella, and their endosymbionts did not grow on MacConkey Agar. Our results suggest that the first EPN species has always retained all its abilities and that endosymbionts have acquired resistance to tetracycline, while experiments with the second EPN species provided some contrasting results in time that will require further investigations.

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. PATIENTS AND METHODS: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. RESULTS: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. CONCLUSIONS: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

Patient-centered communication, patient satisfaction, and retention in care in assisted reproductive technology visits.

PURPOSE: To explore the association between patient-centered communication, patients' satisfaction, and retention in care in assisted reproductive technology (ART) visits. METHODS: ART visits at eight Italian clinics were videotaped and coded using the Roter Interaction Analysis System, which includes a Patient-Centered Index (PCI), a summary "patient-centered communication" ratio. After the visit, patients completed a satisfaction questionnaire (SATQ). After 3 months, patients were asked about their retention in care. Spearman correlations and Mann-Whitney tests were used to test associations between the study variables; the open-ended item of SATQ was analyzed through content analysis. RESULTS: Eighty-five visits were videotaped (involving 28 gynecologists and 160 patients). PCI score (µ = 0.51 ± 0.28) revealed a more disease-oriented communication during the visit. Patients reported high levels of satisfaction with the visit and identified in the information provision or in the doctor's humanity or kindness the main reasons of satisfaction. At the follow-up, the majority of the couples declared to have followed the clinicians' recommendations and to have remained related to the ART center. No associations were found among the study variables, except for a lower male satisfaction among couples who declared to have changed ART clinic. CONCLUSIONS: Contrary to what was expected, the style of physician-patient communication was not found to be associated with patient satisfaction and retention in care. However, patients were highly satisfied and engaged. The actual meaning of a communication that is "patient-centered" in the ART context might be wider, including the couples' need for information, as suggested by qualitative findings.

Doctor-couple communication during assisted reproductive technology visits.

STUDY QUESTION: What are the characteristics of doctor-couple communication content during actual ART visits? SUMMARY ANSWER: Physicians were mainly focused on providing biomedical information, while communication content from couples had a 2-fold focus on providing biomedical information and on positive talk. WHAT IS KNOWN ALREADY: Communication aspects in ART seem crucial for clinical decision-making, retention in care and critical conversations with couples due to low treatment success rates. However, no studies have been carried out on the actual interaction between the doctor and the couple in this context. STUDY DESIGN, SIZE, DURATION: This observational study involved 28 clinicians and 160 patients referred to eight Italian ART clinics during a one-year recruitment period. PARTICIPANTS/MATERIALS, SETTING, METHODS: ART visits at eight Italian clinics were videotaped. The visits were coded using the Roter Interaction Analysis System (RIAS), particularly focusing on RIAS composite categories, verbal dominance and patient-centeredness score. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 85 visits were eligible for analysis (62% acceptance rate), involving 28 clinicians and 160 patients (including 75 couples). The average visit duration was 37 ± 17.7 min. The mean verbal dominance was 1.9 ± 0.86 (range: 0.72-5.74). Physicians mainly focused on providing biomedical information. Communication content from couples had a 2-fold focus on providing biomedical information and on positive talk. The mean of patient centeredness index (PCI) was 0.51 (SD = 0.28; range 0.08-1.77); visits in which the doctor was a woman or the treatment indication was for heterologous fertilization showed higher PCI scores. Overall, females accounted for 67% of all patient talk. Taking this imbalance into account as expected frequencies for each composite category, males reported significantly more utterances in almost all of the socioemotional categories. LIMITATIONS, REASONS FOR CAUTION: These results are preliminary and observational and only regard Italy. Communication during visits may have been biased since the professionals who agreed to participate showed an interest in communication issues. Another limitation is a possible Hawthorne effect due to the fact that participants were aware of being videotaped. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that ART physicians mainly adopted an informative model of communication and a more disease-oriented approach. Findings revealed the complexity of communication content during ART consultations, given its triadic characteristic in which the third party is also a patient; clinicians should be aware of this complex aspect and of the specific male and female perspectives to be taken into account. The results could be useful for training ART professionals. STUDY FUNDING/COMPETING INTEREST(S): This study was possible thanks to an unconditional grant from Ferring Spa to the Department of Health Sciences, University of Milan. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

THE EURADOS-KIT TRAINING COURSE ON MONTE CARLO METHODS FOR THE CALIBRATION OF BODY COUNTERS.

Monte Carlo (MC) methods are numerical simulation techniques that can be used to extend the scope of calibrations performed in in vivo monitoring laboratories. These methods allow calibrations to be carried out for a much wider range of body shapes and sizes than would be feasible using physical phantoms. Unfortunately, nowadays, this powerful technique is still used mainly in research institutions only. In 2013, EURADOS and the in vivo monitoring laboratory of Karlsruhe Institute of Technology (KIT) organized a 3-d training course to disseminate knowledge on the application of MC methods for in vivo monitoring. It was intended as a hands-on course centered around an exercise which guided the participants step by step through the calibration process using a simplified version of KIT's equipment. Only introductory lectures on in vivo monitoring and voxel models were given. The course was based on MC codes of the MCNP family, widespread in the community. The strong involvement of the participants and the working atmosphere in the classroom as well as the formal evaluation of the course showed that the approach chosen was appropriate. Participants liked the hands-on approach and the extensive course materials on the exercise.

Biodiversity of entomopathogenic nematodes in Italy.

An investigation was carried out on the distribution and biodiversity of steinernematid and heterorhabdtid entomopathogenic nematodes (EPN) in nine regions of Italy in the period 1990-2010. More than 2000 samples were collected from 580 localities and 133 of them yielded EPN specimens. A mapping of EPN distribution in Italy showed 133 indigenous EPN strains belonging to 12 species: 43 isolates of Heterorhabditis bacteriophora, 1 of H. downesi, 1 of H. megidis, 51 of Steinernema feltiae, 12 of S. affine, 4 of S. kraussei, 8 of S. apuliae, 5 of S. ichnusae, 3 of S. carpocapsae, 1 of S. vulcanicum, 3 of Steinernema 'isolate S.sp.MY7' of 'S. intermedium group' and 1 of S. arenarium. Steinernematids are more widespread than heterorhabditids and S. feltiae and H. bacteriophora are the most commonly encountered species. Sampling sites were grouped into 11 habitats: uncultivated land, orchard, field, sea coast, pinewood, broadleaf wood, grasslands, river and lake borders, caves, salt pan and moist zones; the soil texture of each site was defined and the preferences of habitat and soil texture of each species was assessed. Except for the two dominant species, S. feltiae and H. bacteriophora, EPN occurrence tends to be correlated with a specific vegetation habitat. Steinernema kraussei, H. downesi and H. megidis were collected only in Sicily and three of the species recently described - S. apuliae, S. ichnusae and S. vulcanicum - are known only from Italy and seem to be endemic.

Structural-equation-modelling of the tropism impact on achieving viral suppression within six months in naïve HIV patients.

INTRODUCTION: Aim of the study was to evaluate the relevance of baseline (BL) plasma tropism of HIV on the achievement of a viral suppression within six months of antiviral therapy (ARV) in naïve patients by a structural-equation-modelling. MATERIALS AND METHODS: Two-hundred and twenty-seven patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by genotopheno algorithm. Booster atazanavir or lopinavir , or efavirenz or nevirapine were used, in combination with either abacavir/lamivudine or tenofovir-emtricitabine. RESULTS: X4-tropism correlate negatively with CD4 cell count at BL and follow-up (FU), and CD4 correlate negatively with BL-plasma viremia (PLV). BL-PLV correlate positively with FU-PLV. We have developed the hypothesis that the variables BL-CD4 and BL-PLV represent a mediators chain among X4-tropism and outcome of plasma viraemia at six months. This model, after structural-equation-modelling (SEM, Stata13), is shown in Figure 1. The indirect effect of X4-tropism on Fup-PLV is significant (p<0.01) but about 10 fold lower than the direct effect by BL-PLV. X4-tropism also has a direct negative effect on BL-CD4 (p<0.001) and an indirect positive effect on BL-PLV (p<0.001), irrespective of the drug regimen. Path model explaining direct and mediated effects of "tro (tropism)," "gender," "age," "cd0 (BL-CD4)" and "lrna0 (BL-PLV)" on the final outcome ("lrna1-Fup-PLV)," where "tro," "gender," and "age" are exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows indicate direct effects. Circles indicate residuals related to endogenous/dependent variables; numbers near to circles are the corresponding variances. CONCLUSIONS: This model shows the relevance of BL-tropism on the outcome of plasma viraemia in naïve patients after six months of therapy, irrespective of drug regimen used.

Upper body force production after a low-volume static and dynamic stretching.

This study investigated the acute effect of a low-volume static and dynamic stretching on maximal isometric peak force (MIPF), time to maximal isometric force (TMIF), rate of force production (RFP) and average amplitude of the surface EMG (AvgEMG) of the main agonist muscles acting on the bench press maximum isometric force exercise. Thirty subjects were randomly divided into three groups: static stretch (SG: 22.8 ± 5.6 years, 176.6 ± 3.5 cm, 74.4 ± 5.9 kg), dynamic stretch (DG: 21.4 ± 3.9 years, 178.4 ± 7.2 cm, 71.7 ± 8.2 kg) and control group (CG: 20.4 ± 3.6 years, 179.8 ± 5.8 cm, 74.4 ± 9.8 kg). SG performed two 30-s repetitions and DG performed 10 repetitions of each of the two different exercises for the pectoralis major and triceps brachii. The MIPF, TMIF, RFP and AvgEMG of the pectoralis major (sternocostal part) and triceps brachii (long and lateral head) were measured before and immediately after the stretching protocols. A significant decrease in the MIPF from pre- to post-stretching was observed in both SG (p <0.001) and DG (p <0.05). No significant differences were found in the CG for all force parameters. No significant differences in the TMIF and RFP from pre- to post-stretching were found in the three groups. The SG showed a significant (p <0.05) decrease in the AvgEMG of the three muscles, whereas no significant differences were found for the DG and CG. These findings suggest that a low-volume static and dynamic stretching adversely affects efforts of muscle maximal strength of the upper limb muscles studied, but it does not seem to affect TMIF or RFP.

Dead layer thickness characterization of an HPGe detector by measurements and Monte Carlo simulations.

To fully characterize the front dead layer (DL) of an HPGe detector at low photon energy range, its intrinsic efficiency curve was measured using a (241)Am radioactive source in 10-60 keV energy range. A comparison between experimental efficiency and MCNPX results showed that the DL value of 0.4 µm initially quoted by the manufacturer has to be changed to 7.5 µm to reproduce measurements.

Simulation of phoswich detectors using MCNPX and EGSNRC.

The in vivo monitoring Lab at KIT uses two phoswich detectors for routine lung counting. A simplified model of one of them has been implemented in the two Monte Carlo codes EGSnrc and MCNPX. The active part of the detector consists of a crystal of NaI(Tl) and one of CsI(Tl): the energy deposited in both the crystals have been studied to consider the effect of the anticoincidence logic, present in the read-out electronics of the detectors and not yet studied with Monte Carlo simulations. Only the NaI(Tl) crystal has then been used to study the escape peaks at several energies, which are more prominent at low energies. The results from the two codes have been compared. The comparison of the codes predictions for the escape peaks has been then extended using the model of a germanium detector.

Erroneously low continuous ScvO2 reading due to red blood cells transfusion.

Hemoglobin oxygen saturation in superior vena cava (ScvO(2)) is used as a parameter to guide hemodynamic management in shock patients and it can be continuously read through a central venous catheter equipped with a fiberoptic spectrophotometric probe (Edwards PreSep catheter) connected to a specific monitor (Edwards Vigileo). We report of an episode of erroneous ScvO(2) reading by this technology in a patient with septic shock who was receiving an erythrocytes transfusion through the PreSep catheter main lumen. We think this artifact should be known by intensivists since it can lead to ScvO(2) misinterpretation and subsequent erroneous therapeutic decisions.

[The incidence of dental caries during childhood. A clinical and epidemiologic study in Matera (Southern Italy)]. / Studio clinico epidemiologico della incidenza di carie dentale in bambini della città di Matera.

AIM: The aim of the present study is to obtain comprehensive epidemiological data of the incidence of oral and dental health conditions in an Italian homogeneous population of schoolchildren. MATERIALS AND METHODS: The study has been performed on schoolchildren born, living and attending the primary school in Matera, Basilicata, Southern Italy. Such data have been compared with the alimentary habits of the participants to the study, as well as with the social-economic family situations and with the social-environmental data. RESULTS: The data show a marked difference in the habits of oral hygiene, and in the health status of the oral structures also, based on both the sex and the environment of life. CONCLUSIONS: Such differences in the prevalence of caries among various urban areas and the behavioural habits related to sex and age ratios may be very useful findings for future regional prevention programs.

Antenatal post-hemorrhagic ventriculomegaly: a prospective follow-up study.

OBJECTIVE: The aim of this study was to evaluate the presence and the severity of neurological and cognitive impairment at 2 years of age in 16 infants (9 term born, 7 preterm of mean gestation 33.6 weeks) with cerebral ventriculomegaly of antenatal onset associated with intraventricular haemorrhage. METHODS: Ventricular dilatation, with or without associated lesions, was, with one exception, not identified on the antenatal routine scan at approximately 22 weeks but was obvious on the scans performed between weeks 27 and 33. In 8 of the 16 cases there were signs of parenchymal involvement or of abnormalities of the corpus callosum or cerebellum. In all patients the diagnosis of antenatal IVH was confirmed by early neonatal imaging. Outcome was measured using the Hammersmith infant neurological examination and the Griffiths developmental scales at 2 years. RESULTS AND CONCLUSIONS: At 2 years, 8 infants had normal motor outcome and 8 had cerebral palsy. The presence and severity of cerebral palsy or neurodevelopmental delay was not always related to the magnitude or symmetry of the ventricular dilatation per se. The presence of associated lesions was a negative prognostic marker. The early development of epilepsy was also associated with an abnormal outcome.

Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia.

The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.

[Nutritional problems in the surgical patients with head and neck tumours. Literature review and personal experience]. / Problematiche nutrizionali nei pazienti chirurgici con patolo- gie oncologiche del distretto cervico-cefalico. Revisione della letteratura alla luce dell'esperienza professionale.

During the last years the importance of the correct nutritional assessment as a part of the therapeutic process of the human pathologies has a greatly increased relevance. Still more in oncology, such relationship among nutritional assessment and good result of the therapeutic treatment have a fundamental importance. Among the neoplastic diseases those of the head and the neck result to be particularly aggressive, both for their nature and for the particular anatomical organization of such body areas, and the affected patients also need a precise evaluation of the nutritional assessment to obtain an optimal therapeutic result. On the basis of such premises and to their own clinical experience, the authors describe the main nutritional problems of the patients with tumours of the head and the neck and the possible therapeutic solutions.

Design, synthesis, and analysis of a polyethelene glycol-modified (PEGylated) small molecule inhibitor of integrin {alpha}4{beta}1 with improved pharmaceutical properties.

Integrin alpha4beta1 plays an important role in inflammatory processes by regulating the migration of leukocytes into inflamed tissues. Previously, we identified BIO5192 [2(S)-{[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino}-4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-amino)-pentanoylamino]-butyric acid], a highly selective and potent (K(D) of 9 pM) small molecule inhibitor of alpha4beta1. Although BIO5192 is efficacious in various animal models of inflammatory disease, high doses and daily treatment of the compound are needed to achieve a therapeutic effect because of its relatively short serum half-life. To address this issue, polyethylene glycol modification (PEGylation) was used as an approach to improve systemic exposure. BIO5192 was PEGylated by a targeted approach in which derivatizable amino groups were incorporated into the molecule. Two sites were identified that could be modified, and from these, five PEGylated compounds were synthesized and characterized. One compound, 2a-PEG (K(D) of 19 pM), was selected for in vivo studies. The pharmacokinetic and pharmacodynamic properties of 2a-PEG were dramatically improved relative to the unmodified compound. The PEGylated compound was efficacious in a rat model of experimental autoimmune encephalomyelitis at a 30-fold lower molar dose than the parent compound and required only a once-a-week dosing regimen compared with a daily treatment for BIO5192. Compound 2a-PEG was highly selective for alpha4beta1. These studies demonstrate the feasibility of PEGylation of alpha4beta1-targeted small molecules with retention of activity in vitro and in vivo. 2a-PEG, and related compounds, will be valuable reagents for assessing alpha4beta1 biology and may provide a new therapeutic approach to treatment of human inflammatory diseases.

[Drug/food interactions: an actual therapeutic outcome]. / Interazioni farmaco-alimentari: un problema terapeutico sempre più attuale.

The biological effects of specific interactions occurring between drugs and foods may greatly vary, determining severe side effects in some people. A lot of factors may influence such interactions, i.e. age, sex, dietary composition, and so. In addition, further interaction may be determined by cigarette smoking, alcohol abuse and coffee consumption. Older people, as well as children, chronic ill and malnourished people seems to be most commonly affected by side effects due to food/drugs interaction. The aim of this review is to give a synopsis of the drug/food interactions most commonly occurring in clinical practice.

An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis.

Integrin alpha 4 beta 1 plays an important role in inflammatory processes by regulating the migration of lymphocytes into inflamed tissues. Here we evaluated the biochemical, pharmacological, and pharmacodynamic properties and efficacy in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, of two types of alpha 4 beta 1 inhibitors, the anti-rat alpha 4 monoclonal antibody TA-2 and the small molecule inhibitor BIO5192 [2(S)-[[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino]-4-[4-methyl-2(S)-(methyl-[2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl]-amino)-pentanoylamino]-butyric acid]. TA-2 has been extensively studied in rats and provides a benchmark for assessing function. BIO5192 is a highly selective and potent (KD of <10 pM) inhibitor of alpha 4 beta 1. Dosing regimens were identified for both inhibitors, which provided full receptor occupancy during the duration of the study. Both inhibitors induced leukocytosis, an effect that was used as a pharmacodynamic marker of activity, and both were efficacious in the EAE model. Treatment with TA-2 caused a decrease in alpha 4 integrin expression on the cell surface, which resulted from internalization of alpha 4 integrin/TA-2 complexes. In contrast, BIO5192 did not modulate cell surface alpha 4 beta 1. Our results with BIO5192 indicate that alpha 4 beta 7 does not play a role in this model and that blockade of alpha 4 beta 1/ligand interactions without down-modulation is sufficient for efficacy in rat EAE. BIO5192 is highly selective and binds with high affinity to alpha 4 beta 1 from four of four species tested. These studies demonstrate that BIO5192, a novel, potent, and selective inhibitor of alpha 4 beta 1 integrin, will be a valuable reagent for assessing alpha 4 beta 1 biology and may provide a new therapeutic for treatment of human inflammatory diseases.