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1.
PLoS One ; 16(12): e0260029, 2021.
Article in English | MEDLINE | ID: mdl-34855775

ABSTRACT

PURPOSE: The purpose of this study was to investigate the changes in structural spectral-domain optical coherence tomography (SD-OCT), OCT Angiography (OCTA) parameters, and visual acuity, 1 year after endoscopic endonasal approach for the removal of an intra-suprasellar pituitary adenoma compressing optic chiasm and compare outcomes with 48 hours postoperative data. METHODS: Sixteen eyes of eight patients (4 males, 4 females, mean age 52 ± 11 years) were enrolled in this prospective study. The primary outcome was to evaluate the changes over time before and after surgery, analyzing the Best Corrected Visual Acuity (BCVA), Ganglion Cell Complex (GCC), Retinal Nerve Fiber Layer (RNFL) thicknesses, the retinal vessel density (VD) of Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), Radial Peripapillary Capillary (RPC) and the Foveal Avascular Zone (FAZ). The secondary outcome was to identify potential biomarkers that could predict visual acuity changes after 1-year follow-up. RESULTS: When comparing SD-OCT and OCTA measurements obtained after 1 year with those observed 48 hours after surgery, GCC and RNFL were significantly improved. After a significant reduction at 48 hours, GCC thickness showed a significant increase at 1 year after surgery (p = 0.007), while a significant restoration of RNFL thickness was found at 1 year (p = 0.005), as well as the VD of SCP, DCP, and RPC values. FAZ area did not change over time. BCVA significantly improved at each time after surgery (p = 0.037, p = 0.013). A statistically significant correlation was found between the preoperative BCVA, VD of SCP, DCP, RPC, and the postoperative BCVA at 1 year (p = 0.017, p = 0.029, p = 0.031, p = 0.023). CONCLUSION: SD-OCT and OCTA provide helpful information to identify the retinal structural and vascular improvements 1 year after surgery. OCTA parameters could serve as potential predictive markers for visual acuity recovery at long-term follow-up.


Subject(s)
Adenoma/surgery , Natural Orifice Endoscopic Surgery/methods , Pituitary Neoplasms/surgery , Retina/diagnostic imaging , Tomography, Optical Coherence/methods , Adenoma/pathology , Adult , Female , Fluorescein Angiography , Humans , Longitudinal Studies , Male , Middle Aged , Nerve Fibers , Pituitary Neoplasms/pathology , Preoperative Care , Prospective Studies , Retina/anatomy & histology , Treatment Outcome , Visual Acuity
2.
Mar Pollut Bull ; 149: 110580, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31546112

ABSTRACT

Marine litter has significant ecological, social and economic impacts, ultimately raising welfare and conservation concerns. Assessing marine litter hotspots or inferring potential areas of accumulation are challenging topics of marine research. Nevertheless, models able to predict the distribution of marine litter on the seabed are still limited. In this work, a set of Artificial Neural Networks were trained to both model the effect of environmental descriptors on litter distribution and estimate the amount of marine litter in the Central Mediterranean Sea. The first goal involved the use of self-organizing maps in order to highlight the importance of environmental descriptors in affecting marine litter density. The second goal was achieved by developing a multilayer perceptron model, which proved to be an efficient method to estimate the regional quantity of seabed marine litter. Results demonstrated that machine learning could be a suitable approach in the assessment of the marine litter issues.


Subject(s)
Environmental Monitoring/methods , Neural Networks, Computer , Waste Products/analysis , Algorithms , Machine Learning , Mediterranean Sea , Sicily
3.
Faraday Discuss ; 206: 497-522, 2018 01 01.
Article in English | MEDLINE | ID: mdl-28944811

ABSTRACT

The vacuum-liquid interfaces of a number of ionic-liquid mixtures have been investigated using the combination of reactive-atom scattering with laser-induced fluorescence detection (RAS-LIF), selected surface tension measurements, and molecular dynamics (MD) simulations. The mixtures are based on the widespread 1-alkyl-3-methylimidazolium ([Cnmim]+) cation, including mixed cations which differ in chain length or chemical functionality with a common anion; and different anions for a common cation. RAS-LIF results imply that the surface compositions exhibit a general form of non-stoichiometric behaviour that mimics the well-known Henry's and Raoult's laws at low and high mole fraction, respectively. The extended Langmuir model provides a moderately good single-parameter fit, but higher-order terms are required for an accurate description. The quantitative relationship between RAS-LIF and surface tension, which probes the surface composition only indirectly, is explored for mixtures of [C2mim]+ and [C12mim]+ with a common bis(trifluoromethylsulfonyl)imide ([NTf2]-) anion. Extended Langmuir model fits to surface tension data are broadly consistent with those to RAS-LIF; however, several other common approaches to extracting surface compositions from measured surface tensions result in much larger discrepancies. MD simulations suggest that RAS-LIF faithfully reports on the alkyl-chain exposure at the surface, which is only subtly modified by composition-dependent structural reorganisation.

4.
Clin Microbiol Infect ; 23(5): 332.e1-332.e9, 2017 May.
Article in English | MEDLINE | ID: mdl-27693528

ABSTRACT

OBJECTIVE: To explore the social, cultural, psychological and organizational factors associated with inequality in the workplace among clinical microbiologists (CM) and infectious disease (ID) specialists in European hospitals. METHODS: We analysed data from 52 interviews and five focus groups involving 82 CM/ID specialists selected from university, research or community hospitals in five countries, one each in Northern, Western, Eastern, Southeastern and Southwestern Europe. The 80 hours of recordings were transcribed, and the anonymous database coding process was cross-checked iteratively by six researchers. RESULTS: Inequality affects all the institutions in all the countries we looked at, denying or reducing access to professional assets with intensity and form that vary largely according to the cultural and organizational context. Discrimination is generally not explicit and uses disrespectful microbehaviours that are hard to respond to when they occur. Inequality affected also loans, distribution of research funds and gender and country representation in boards and conference faculty. Parenthood has a major impact on women's careers, as women are still mainly responsible for family care. Responses to discrimination range from reactive to surrender strategies. CONCLUSIONS: Our study offers an effective model for diagnosing discriminatory behaviours in a medical professional setting. Knowledge of inequality's drivers could help national ID/CM societies in collaboration with major European stakeholders to further reduce such discrimination. The effect of discrimination on the quality of healthcare in Europe needs further exploration.


Subject(s)
Communicable Diseases , Microbiology , Physicians , Specialization , Education, Medical , Europe , Female , Hospitals , Humans , Male , Societies, Medical , Socioeconomic Factors , Workplace
5.
Chemistry ; 22(16): 5534-7, 2016 Apr 11.
Article in English | MEDLINE | ID: mdl-26938670

ABSTRACT

Conformational constrained ß-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the ß-hairpin peptide. The entity of the stability of the ß-hairpin peptide depends on the length of the bridge.


Subject(s)
Peptides/chemistry , Triazoles/chemistry , Amino Acid Sequence , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Models, Molecular , Protein Conformation
6.
Neurobiol Learn Mem ; 124: 71-87, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26220900

ABSTRACT

Autism Spectrum Disorders are a heterogeneous group of neurodevelopmental disorders, with rising incidence but little effective therapeutic intervention available. Currently two main clinical features are described to diagnose ASDs: impaired social interaction and communication, and repetitive behaviors. Much work has focused on understanding underlying causes of ASD by generating animal models of the disease, in the hope of discovering signaling pathways and cellular targets for drug intervention. Here we review how ASD behavioral phenotypes can be modeled in the mouse, the most common animal model currently in use in this field, and discuss examples of genetic mouse models of ASD with behavioral features that recapitulate various symptoms of ASD.


Subject(s)
Autism Spectrum Disorder/genetics , Disease Models, Animal , Translational Research, Biomedical , Aggression/physiology , Animals , Autism Spectrum Disorder/psychology , Compulsive Behavior/genetics , Humans , Interpersonal Relations , Memory Disorders/genetics , Mice , Motor Activity/genetics , Obsessive Behavior/genetics , Phenotype , Signal Transduction , Vocalization, Animal/physiology
7.
Musculoskelet Surg ; 98(1): 53-60, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23979725

ABSTRACT

PURPOSE: Pediatric closed femoral shaft fractures are commonly related to a good prognosis. There is no consensus on treatment. We aimed to evaluate the treatment, features, radiological findings and management strategies, creating an algorithm of treatment. MATERIALS AND METHODS: Fifty-two simple femoral shaft fractures in children were retrospectively evaluated for age and gender distribution, side of the fracture, etiology of injuries, limb length discrepancy, range of knee and hip motion and parents satisfaction with a mean clinical and radiographic follow-up of 3 years and 6 months. Twenty-eight patients were treated with reduction and early hip spica cast while 24 patients were treated with external fixation (EF). RESULTS: Nearly 58 % of the cases were caused by traffic accidents and were predominantly male (61.5 %). Most of the fractures were of the middle femoral shaft (57.6 %). Muscle strength was normal (MRC scale) in all patients with no pain (NIPS and PRS scale). Knee and Hip range of motion were similar in both types of treatment. Patients treated with EF had shorter limb length discrepancy compared with SC. There were no reports of re-fracture. We found a higher familiar satisfaction in patients treated with EF. CONCLUSIONS: An algorithm for the management of femoral shaft fractures in the pediatric population is proposed. Results on the study population gave raise to a satisfactory clinical and radiological results.


Subject(s)
Algorithms , Disease Management , Femoral Fractures/therapy , Fracture Fixation/methods , Accidental Falls , Accidents, Traffic , Athletic Injuries/therapy , Bone Nails , Bone Remodeling , Casts, Surgical , Child , Child, Preschool , Exercise , Female , Femoral Fractures/complications , Femoral Fractures/diagnostic imaging , Femoral Fractures/economics , Follow-Up Studies , Fracture Fixation, Internal , Humans , Infant , Infant, Newborn , Leg Length Inequality/epidemiology , Leg Length Inequality/etiology , Male , Patient Satisfaction , Radiography , Range of Motion, Articular , Recovery of Function , Retrospective Studies , Socioeconomic Factors , Surveys and Questionnaires
8.
J. venom. anim. toxins incl. trop. dis ; 15(2): 305-324, 2009. mapas, tab
Article in English | LILACS, Sec. Est. Saúde SP | ID: lil-517288

ABSTRACT

Despite measures adopted to control American visceral leishmaniasis (AVL), the disease is spreading in a fast and worrying way throughout western São Paulo state. The aim of this work was to study the variables involved in the disease cycle as well as the effectiveness of controlling measures. The study was carried out in the microregion of Dracena, which is composed of twelve cities and belongs to Alta Paulista, a region of western São Paulo. The necessary data were provided by the Superintendence for Endemic Disease Control and Adolfo Lutz Institute, Regional Laboratory of Presidente Prudente. From August 2005 to January 2008, the following factors were observed: detection of phlebotomine sandflies in the cities and periods in which dogs or humans were diagnosed; number of human deaths; prevalence of suspected dogs tested by serology; percentage of euthanasia in suspected dogs; a possible correlation between positive dogs and cases of the disease in humans; and the disease prevalence among municipalities from the studied region. It was verified that, despite the strategies adopted in Dracena microregion to control AVL, the disease continues to rise. Thus, some procedures of the AVL Monitoring and Control Program should be reviewed, to grant the initiative more credibility and effectiveness.


Subject(s)
Leishmaniasis, Visceral/prevention & control , Seroepidemiologic Studies
11.
Pediatr Pulmonol ; 30(6): 445-52, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11109055

ABSTRACT

The prevalence of moderate to severe sleep-disordered breathing (SDB) in patients with myelomeningocele may be as high as 20%, but little information is available regarding treatment of these patients. To assess the efficacy and complications of treatments for these children, we collected data on 73 patients from seven pediatric sleep laboratories. Obstructive sleep apnea (OSA, n = 30) and central apnea (n = 25) occurred more frequently than central hypoventilation (n = 12). We also describe a sleep-exacerbated restrictive lung disease type of SDB in 6 patients who had hypoxemia during sleep without apnea or central hypoventilation. For each type of SDB, effective treatments were identified in a stepwise process, moving towards more complex and invasive therapies. For OSA, adenotonsillectomy was often ineffective (10/14), whereas nasal continuous positive airway pressure (CPAP) was usually successful (18/21). For central apnea, methylxanthines and/or supplemental oxygen proved sufficient in 2 of 9 and 3 of 6, respectively, but noninvasive positive pressure ventilation was required in 7 children. For central hypoventilation, supplemental oxygen (alone or with methylxanthines), noninvasive positive pressure ventilation, and tracheostomy with positive pressure ventilation were effective in 3, 2, and 2 patients, respectively. Sleep-exacerbated restrictive lung disease always required supplemental oxygen treatment, but in 2 cases also required noninvasive positive pressure ventilation; nutritional and orthopedic procedures also were helpful. Posterior fossa decompression was used for the first three types of SDB, but data were insufficient to delineate specific recommendations for or against its use. In summary, evaluation by an experienced, multidisciplinary team can establish an effective treatment regime for a child with myelomeningocele and SDB.


Subject(s)
Sleep Apnea Syndromes/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Meningomyelocele/complications , Oximetry , Oxygen Inhalation Therapy , Respiratory Physiological Phenomena , Risk Factors , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/diagnosis , Sleep Apnea, Central/therapy , Sleep Apnea, Obstructive/therapy , Tonsillectomy
12.
Spine (Phila Pa 1976) ; 25(14): 1795-802, 2000 Jul 15.
Article in English | MEDLINE | ID: mdl-10888948

ABSTRACT

STUDY DESIGN: A radiographic assessment has been developed to include coronal, sagittal, and axial parameters. OBJECTIVE: To determine the correlation of postoperative radiographic results and percentage postoperative radiographic improvement with patient clinical self-assessment. SUMMARY OF BACKGROUND DATA: With the increasing interest in outcome studies, the authors wanted to determine whether Scoliosis Research Society clinical questionnaire results would correlate with objective radiographic improvement. INCLUSION CRITERIA: adolescent idiopathic scoliosis treated with anterior or posterior instrumentation, a solid fusion, minimum 2-year follow-up, and a completed postoperative Scoliosis Research Society questionnaire. Seventy-eight patients met the criteria. Measurements included in the radiographic score: Cobb angles of the coronal curve, C7 to the center sacral vertical line, apical translation, apical vertebral rotation, T1 rib angle, end-instrumented vertebrae angulation, angulation of the disc below the end-instrumented vertebra, and curve type. Sagittal measurements included T2-T12, T5-T12, T2-T5, T12-L2, and L1-S1. RESULTS: The preoperative radiographic score of these 78 patients was mean 60.1 +/- 9.7 (range 41-88, maximum radiographic score, 100). The 2-year postoperative radiographic score was mean 83.8 +/- 8.8 (range, 65-100). The median Scoliosis Research Society questionnaire score was 98 +/- 12.3 (range, 58-116, maximum score, 125, showing that the patient is highly satisfied and asymptomatic). The postoperative radiographic score versus the questionnaire score showed a Spearman rank correlation of 0.04 (P = 0.68, little or no correlation throughout). Percentage improvement of the radiographic score versus the questionnaire score showed a Spearman rank correlation of 0.1 (P = 0.38, little or no correlation throughout). CONCLUSION: In this initial group of patients, the radiographic assessment shows a significant improvement between preoperative and 2-year postoperative scores. However, little correlation between the radiographic assessment and the questionnaire scores was found in this adolescent population, suggesting that separate analyses of radiographic and clinical outcome data are required when evaluating results of postoperative scoliosis surgery.


Subject(s)
Patient Satisfaction , Scoliosis/diagnostic imaging , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Male , Radiography , Scoliosis/surgery , Spinal Fusion/instrumentation , Spinal Fusion/methods , Surveys and Questionnaires , Treatment Outcome
13.
Am J Cardiol ; 85(9): 1131-6, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10781765

ABSTRACT

The aim of this study was to assess the effects of endurance training on myocardial regional systolic and diastolic function by pulsed Doppler tissue imaging (DTI). Twenty male water polo players and 20 male control subjects underwent standard Doppler echocardiography and pulsed DTI, performed in apical views by placing a sample volume on left ventricular (LV) basal septal and inferior walls. Age, body surface area, and blood pressure were comparable between the 2 groups, with lower heart rate in athletes (p <0.001). They had significantly increased LV mass index (due to both higher wall thickness and end-diastolic diameter), greater endocardial fractional shortening, higher transmitral early/atrial (E/A) peak velocities ratio. In athletes, DTI analysis showed significantly prolonged myocardial deceleration time and greater myocardial E/A peak velocity ratio of septal and inferior walls, whereas myocardial early peak velocity was increased (p <0.01) only at the inferior wall. In the overall group, we found univariate relations of septal and inferior E/A peak velocity ratio and myocardial deceleration time with LV mass levels, and, in particular, with the sum of wall thickness. By separate multivariate analyses, however, these relations disappeared, being dependent on heart rate degree. Another association found between LV end-diastolic diameter and myocardial early diastolic wave peak velocity of the inferior wall (r = 0.68, p <0.0001) remained significant (standardized beta coefficient 0.60, p <0.00001), even after adjusting for heart rate, body surface area, age, and stroke volume (R(2) = 0.71, p <0.00001). In conclusion, DTI is a useful tool for detecting regional changes in myocardial function induced by training, because athletes present with an improvement in diastolic passive properties of myocardium. The higher early diastolic velocity of the inferior wall and its relation to increased preload may represent an indicator of aerobic training, allowing quantification of the degree of LV adaptation to endurance exercise.


Subject(s)
Diastole/physiology , Echocardiography, Doppler, Pulsed , Heart Ventricles/diagnostic imaging , Sports , Ventricular Function, Left/physiology , Adult , Dilatation, Pathologic , Heart Ventricles/pathology , Humans , Male , Sports/physiology
14.
Spine (Phila Pa 1976) ; 25(7): 813-8, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10751292

ABSTRACT

STUDY DESIGN: Retrospective analysis of radiographs on a prospective cohort of patients undergoing anterior instrumentation for thoracic idiopathic scoliosis. OBJECTIVES: To analyze the change in sagittal profile after growth. SUMMARY OF BACKGROUND DATA: The authors previously reported some advantages of anterior instrumentation for treatment of thoracic idiopathic scoliosis. However, postsurgery hyperkyphosis has resulted in some patients, especially those who were skeletally immature at the time of surgery. METHODS: Inclusion criteria required that participants have thoracic idiopathic scoliosis treated with anterior instrumentation and a confirmed solid fusion, no rod breakage, and a minimum follow-up period of 2 years. The 47 patients meeting the criteria were divided into a study group of 10 patients who were Risser 0 at the time of surgery and a control group of 37 patients who were Risser 1 to 5. Progressive sagittal kyphosis was defined as an increase of 10 degrees or more (T5-T12) after surgery. RESULTS: Sagittal progression greater than 10 degrees (average, 15 degrees ) occurred in 6 of 10 patients (60%) in the study group (Risser 0). Five patients progressed from 10 degrees to 19 degrees, and one patient from 20 degrees to 30 degrees. In contrast, sagittal progression occurred in only 10 of 37 patients (27%) in the control group (Risser 1 to 5). CONCLUSIONS: Some patients with thoracic adolescent idiopathic scoliosis treated with anterior instrumentation may be at risk for progressive sagittal kyphosis secondary to growth. Skeletal immaturity (Risser 0) appears to be a risk factor. In these immature patients, preserving the sagittal profile with intervertebral spacers, rigid rods, and bone graft (allowing for an average 15 degrees increase of kyphosis with growth) may be appropriate.


Subject(s)
Scoliosis/physiopathology , Scoliosis/surgery , Spinal Fusion/instrumentation , Thoracic Vertebrae/growth & development , Adolescent , Bone Nails , Child , Cohort Studies , Female , Humans , Kyphosis/diagnostic imaging , Kyphosis/etiology , Male , Radiography , Retrospective Studies , Risk Factors , Scoliosis/diagnostic imaging , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery
15.
Int J Emerg Ment Health ; 2(1): 33-41, 2000.
Article in English | MEDLINE | ID: mdl-11232102

ABSTRACT

The role of the Mental Health Professional (MHP) on Critical Incident Stress Management (CISM) teams has been described as one of assess and refer. That is, to assess participants who are reacting strongly to a critical incident and refer them for additional psychological help. The purpose of this article is to present guidelines, from practice and from the research literature, for MHPs to use to help them predict which participants are likely to experience high-stress reactions following the critical incident. The stages of a CISD are briefly described and the predictive features associated with each stage are discussed.


Subject(s)
Crisis Intervention/methods , Emergency Medical Services , Guidelines as Topic , Health Personnel , Mental Health Services , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology , Humans , Workforce
16.
Eur Cytokine Netw ; 10(2): 227-36, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10400829

ABSTRACT

The role of the polymorphonuclear leukocyte (PMN) cytoskeleton during the transmigration across colonic epithelial cells is not very well understood. In order to study the role of different components of the PMN cytoskeleton during transepithelial migration across a colonic epithelial cell monolayer (T84), PMN were preincubated with drugs affecting either the actin cytoskeleton (cytochalasin B, iota toxin of Clostridium perfringens, and phalloidin) or the microtubules (colchicine and taxol). The role of PMN myosin during transepithelial migration was investigated using the inhibitor 2,3-butanedione monoxime (BDM) and DC3B toxin. PMN intracellular Ca2+, during neutrophil adhesion and translocation across the epithelium, was assessed by the Ca2+ chelator 1, 2bis-(2-aminophenoxy)-ethane-N,N,N', N'-tetra-acetic acid tetrakis (acetoxymethyl) ester (BAPTA-AM). Transmigration of PMN was initiated by applying either interleukin-8 or formyl-met-leu-phe (fMLP). While colchicine and taxol preexposure did not influence PMN transepithelial migration, treatment with cytochalasin B, iota toxin, phalloidin, BDM, DC3B toxin and BAPTA-AM greatly diminished migration of PMN across T84 monolayers. Similarly, cell-cell contacts established between PMN and epithelial cells during the transmigration were diminished after treatment of PMN with iota toxin or cytochalasin B. These data show that the neutrophil actin cytokeleton and myosin, but not the microtubules, evoke a Ca2+ -dependent motility that facilitates migration across the colonic epithelial barrier.


Subject(s)
ADP Ribose Transferases , Actins/physiology , Chemotaxis, Leukocyte/drug effects , Interleukin-8/pharmacology , Intestinal Mucosa/cytology , Microtubules/physiology , Myosins/physiology , Neutrophils/physiology , Bacterial Toxins/pharmacology , Calcium/metabolism , Cell Adhesion/drug effects , Cells, Cultured , Chelating Agents/pharmacology , Colchicine/pharmacology , Colonic Neoplasms/pathology , Cytochalasin B/pharmacology , Cytoskeleton/drug effects , Cytoskeleton/physiology , Cytoskeleton/ultrastructure , Diacetyl/analogs & derivatives , Diacetyl/pharmacology , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Epithelial Cells/cytology , Humans , Microtubules/drug effects , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , Neutrophils/drug effects , Neutrophils/ultrastructure , Paclitaxel/pharmacology , Phalloidine/pharmacology , Tumor Cells, Cultured
17.
Biopolymers ; 47(1): 5-22, 1998.
Article in English | MEDLINE | ID: mdl-9692324

ABSTRACT

The present paper highlights and reviews current research in the field of hemoprotein models. Hemoproteins have been extensively studied in order to understand structure-function relationships, and to design new molecules with desired functions. A wide number of synthetic analogues have been developed, using quite different approaches. They differ in molecular structures, ranging from simple meso-substituted tetraaryl-metalloporphyrins and peptide-porphyrin conjugates. In this paper we summarize the state of the art on peptide based hemoprotein models. We also report here the approach used by us to develop a new class of molecules, named mimochromes. They can be regarded as miniaturized hemoproteins, because mimochromes are low molecular weight compounds with some structural and functional properties common to those of the parent high molecular weight protein. The basic structure of mimochromes is a deuteroporphyrin ring covalently linked to two helical peptide chains. Two molecules of this series have been fully characterized. All the information derived from their structural analysis has been applied to the design of new analogues with additional functions.


Subject(s)
Hemeproteins/chemistry , Amino Acid Sequence , Biopolymers/chemistry , Drug Design , Hemeproteins/chemical synthesis , Models, Chemical , Models, Molecular , Molecular Sequence Data , Molecular Weight , Porphyrins/chemical synthesis , Porphyrins/chemistry
18.
J Leukoc Biol ; 63(3): 312-20, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9500518

ABSTRACT

A variety of bacterial enterocolitis in their active stages are characterized by the migration of polymorphonuclear leukocytes (PMNs) across epithelial surfaces. These mechanisms could explain some effects of enterotoxins observed in the intestinal mucosae. Here, using specific inhibitors, we investigated the potential role of CD10 (E.C. 3.4.24.11), present at the surface of human neutrophils, on formyl-Met-Leu-Phe (fMLP)-induced PMN migration across cultured monolayers of the human intestinal cell line T84. Transmigration of human neutrophils across T84 epithelial cells was observed for concentrations of fMLP as low as 10(-9) M, whereas maximal effect was achieved at 10(-7) M as determined by transepithelial resistances and PMN myeloperoxidase assays. RB25, a CD10 inhibitor, reduced by two orders of magnitude the concentration of fMLP required to obtain full neutrophil transmigration across T84 epithelial cell line. RB25 response was concentration dependent with half-maximal and maximal effect occurring at 10(-9) and 10(-7) M, respectively. These concentrations of RB25 corresponded exactly to the half-maximal and maximal inhibition of endopeptidase 24.11 at the neutrophil cell surface. However, the effect of CD10 inhibitors on PMN transmigration cannot be accounted for by a direct action on T84 epithelial cells, since these cells fail to express any detectable endopeptidase 24.11 activity. Moreover, blocking of CD10 enzymatic activity by various and selective inhibitors potentiated the effect of low concentrations of fMLP on PMN transmigration. Finally, RB25 failed to affect interleukin-8 (IL-8)-induced PMN transmigration across T84 epithelial cells, in agreement with the preference of CD10 for small peptidic substrates. Taken together, these results demonstrate that inhibition of CD10 significantly reduced the concentration of fMLP needed for eliciting transmigration of PMN across intestinal epithelia.


Subject(s)
Benzylidene Compounds/pharmacology , Chemotaxis, Leukocyte/physiology , Glycine/analogs & derivatives , Intestinal Mucosa/physiology , Neprilysin/antagonists & inhibitors , Neutrophils/physiology , Chemotaxis, Leukocyte/drug effects , Colonic Neoplasms , Drug Synergism , Enzyme Inhibitors/pharmacology , Glycine/pharmacology , Humans , In Vitro Techniques , Neprilysin/blood , Neutrophils/drug effects , Peroxidase/blood , Tumor Cells, Cultured
20.
Bioorg Med Chem Lett ; 8(10): 1153-6, 1998 May 19.
Article in English | MEDLINE | ID: mdl-9871726

ABSTRACT

We report here the synthesis and preliminary pharmacological characterization of a novel Neurokinin A receptor antagonist. This molecule contains a dehydroalanine residue. It displays a high conformational rigidity and possesses very high activity. Its pharmacological properties as a neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and were compared to those of Neuronorm and MEN10627.


Subject(s)
Alanine/analogs & derivatives , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/pharmacology , Receptors, Neurokinin-2/antagonists & inhibitors , Amino Acid Sequence , Animals , Male , Models, Molecular , Molecular Structure , Peptides, Cyclic/chemistry , Protein Conformation , Rats , Structure-Activity Relationship , Vas Deferens/drug effects , Vas Deferens/physiology
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