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1.
Sports Biomech ; : 1-16, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38190252

ABSTRACT

This study aimed to evaluate the validity and reliability of a wearable device and a phone application for measuring spatiotemporal parameters and their relationship with running economy (RE) by comparing them with photocell data in runners of different abilities. Twenty-three male runners were divided into well-trained and recreational groups and performed a 4-min running bout at 17 and 13 km·h-1 respectively. During the bout, were measured the spatiotemporal parameters with three devices (Stryd, Runmatic, and Optojump) and RE with a gas analyser. Pearson correlation showed perfect relationships for stride frequency (SF) and stride length (SL) between the devices, and moderate for flight time (FT) and contact time (CT). There were no correlations between the spatiotemporal parameters and RE measurements. Coefficient of variation was ~ 5% in all devices for CT, SF, and SL, and higher for FT (15-24%). CT was underestimated (15-16% with Runmatic and Stryd, respectively) and FT was overestimated (36-40%) compared to Optojump. Bland-Altman plots revealed that Runmatic could be a more accurate system than Stryd. In conclusion, both devices were valid tools for measuring spatiotemporal parameters during running at RE speed. Runmatic was more valid and reliable in comparison with Stryd. In addition, at lower running speeds the devices showed less reliability.

2.
Ann Ig ; 35(6): 617-630, 2023.
Article in English | MEDLINE | ID: mdl-37796469

ABSTRACT

Background: During the COVID-19 pandemic, the paediatric population plays a minor role in the spread of the SARS-CoV-2 virus. However, in order to keep schools open and reduce SARS-CoV spreading, it is necessary to identify and isolate early SARS-CoV-2 positive paediatric patients even if they are asymptomatic. The aim of this study was to describe a setting for SARS-CoV 2 testing based on the spontaneous presentation of paediatric patients attending school without a medical prescription and explore its appropriateness. Study design: Cross-sectional study. Methods: The study performed between September 2020 and March 2021 among a sample of 13,283 paediatric patients who underwent a swab in four different hospital settings (school hot spot, emergency department, day hospital setting and hospital wards). For each patients we collected: date of swab execution, type of swab, execution setting of the swab, result of the swab, information about community spread of the virus in the 14 days prior to the swab execution, sex and age. Results: In our sample, females accounted for 45.8%. The median age was 6.8 years (IQR 3.0-11.2) and the most frequent age category was between 6 and 11 years (27.9%). At multivariable models with a swab tested positive as outcome. The swabs executed in all the hospital settings had a lower likelihood of resulting positive compared with the school hot spot setting. Compared with adolescents aged between 14 and 19 years old, new-borns below 3 months (adjOR 1.83, 95% C.I. 1.14-3) and patients aged between 11 and 14 years old (adjOR 1.32, 95% C.I. 1.07-1.63) reported a higher probability of a swab tested positive. Instead, children aged between 3 months and 3 years (adjOR 0.77, 95% C.I. 0.61-0.96) and children aged between 3 years and 6 years (adjOR 0.66, 95% C.I. 0.53-0.83) were less likely to result positive. The higher was the mean of pooled Rt in the 14 days preceding the swab, the higher was the likelihood of resulting positive (adjOR 1.75, 95% C.I. 1.53-1.99). Conclusion: In conclusion, we found a high incidence of paediatric patients positive to the test for the detection of SARS-CoV-2 at the school hot spot compared with other settings during the period of observation. The free access modality to the nasopharyngeal swab was effective in identifying patients with COVID-19. Public health authorities should implement these testing modality in order to help reduce the spread of SARS-CoV-2 in school settings.


Subject(s)
COVID-19 , SARS-CoV-2 , Female , Adolescent , Humans , Child , Child, Preschool , Infant , COVID-19/diagnosis , COVID-19/epidemiology , Pandemics , Cross-Sectional Studies , COVID-19 Testing
3.
Life Sci Space Res (Amst) ; 18: 1-11, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30100142

ABSTRACT

As manned spaceflights beyond low Earth orbit are in the agenda of Space Agencies, the concerns related to space radiation exposure of the crew are still without conclusive solutions. The risk of long-term detrimental health effects needs to be kept below acceptable limits, and emergency countermeasures must be planned to avoid the short-term consequences of exposure to high particle fluxes during hardly predictable solar events. Space habitat shielding cannot be the ultimate solution: the increasing complexity of future missions will require astronauts to protect themselves in low-shielded areas, e.g. during emergency operations. Personal radiation shielding is promising, particularly if using available resources for multi-functional shielding devices. In this work we report on all steps from the conception, design, manufacturing, to the final test on board the International Space Station (ISS) of the first prototype of a water-filled garment for emergency radiation shielding against solar particle events. The garment has a good shielding potential and comfort level. On-board water is used for filling and then recycled without waste. The successful outcome of this experiment represents an important breakthrough in space radiation shielding, opening to the development of similarly conceived devices and their use in interplanetary missions as the one to Mars.


Subject(s)
Astronauts , Cosmic Radiation/adverse effects , Radiation Protection/instrumentation , Space Suits/standards , Clothing , Humans , Models, Theoretical , Phantoms, Imaging , Radiation Dosage , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Space Flight
4.
EBioMedicine ; 25: 112-121, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29100778

ABSTRACT

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1ß, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study.


Subject(s)
Biomarkers/blood , Severity of Illness Index , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/drug therapy , Adult , Aged , Antitubercular Agents , Drug Combinations , Ethambutol/administration & dosage , Female , Humans , Isoniazid/administration & dosage , Male , Middle Aged , Pyrazinamide/administration & dosage , Rifampin/administration & dosage , Treatment Outcome , Tuberculosis, Pulmonary/pathology
5.
Pathologica ; 108(3): 148-150, 2016 Sep.
Article in English | MEDLINE | ID: mdl-28195268

ABSTRACT

Vulvar tumors are not very common and account for about 4% of all cancers affecting the female genital organs. Frequently, malignant neoplasia of this site have squamous phenotype and the rare cases of metastasization are reported in the locoregional lymph nodes and in the surrounding organs. We report a case of metastasization of a vulvar squamous cell carcinoma in an unusual place such as the parietal pleura, in a relapsing patient that was submitted to a surgical vulvectomy the previous year.


Subject(s)
Carcinoma, Squamous Cell/secondary , Pleural Effusion, Malignant/pathology , Pleural Neoplasms/secondary , Vulvar Neoplasms/pathology , Aged , Biomarkers, Tumor/analysis , Biopsy , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/complications , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/etiology , Pleural Neoplasms/chemistry , Pleural Neoplasms/complications , Predictive Value of Tests , Tomography, X-Ray Computed
6.
Curr Mol Med ; 14(2): 246-54, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24467204

ABSTRACT

The caspases are a family of ubiquitously expressed cysteine proteases best known for their roles in programmed cell death. However, caspases play a number of other roles in vertebrates. In the case of caspase-8, loss of expression is an embryonic lethal phenotype, and caspase-8 plays roles in suppressing cellular necrosis, promoting differentiation and immune signaling, regulating autophagy, and promoting cellular migration. Apoptosis and migration require localization of caspase-8 in the periphery of the cells, where caspase-8 acts as part of distinct biosensory complexes that either promote migration in appropriate cellular microenvironments, or cell death in inappropriate settings. In the cellular periphery, caspase-8 interacts with components of the focal adhesion complex in a tyrosine-kinase dependent manner, promoting both cell migration in vitro and metastasis in vivo. Mechanistically, caspase-8 interacts with components of both focal adhesions and early endosomes, enhancing focal adhesion turnover and promoting rapid integrin recycling to the cell surface. Clinically, this suggests that the expression of caspase-8 may not always be a positive prognostic sign, and that the role of caspase-8 in cancer progression is likely context-dependent.


Subject(s)
Caspase 8/metabolism , Cell Movement/physiology , Animals , Apoptosis/genetics , Apoptosis/physiology , Caspase 8/genetics , Cell Movement/genetics , Humans
7.
Radiol Med ; 116(2): 302-9, 2011 Mar.
Article in English, Italian | MEDLINE | ID: mdl-21076886

ABSTRACT

PURPOSE: This study retrospectively analysed the results of biopsies obtained during percutaneous vertebroplasty (PVP) in patients with presumed osteoporotic vertebral compression fractures, with a view to highlighting the importance of coaxial biopsy in determining the aetiology of vertebral fractures and planning subsequent treatment. MATERIALS AND METHODS: Between November 2003 and March 2009, 98 patients (78 women; 20 men) with a clinical and imaging suspicion of osteoporotic vertebral compression fractures underwent coaxial biopsy in conjunction with PVP of the thoracic and lumbar vertebrae. Mean age at the time of the procedure was 72.6 years. A pathologist interpreted all the biopsy samples. RESULTS: In 83 patients, the biopsy results were consistent with the presumed osteoporotic aetiology. In two patients, a malignancy was identified. Biopsy samples from 13 patients were considered insufficient or unsuitable by the pathologist for evaluation. CONCLUSIONS: Despite the number of biopsy samples considered insufficient or unsuitable, coaxial biopsy during PVP is useful in verifying the presumed aetiology of vertebral compression fractures, which is often unclear on the basis of clinical and imaging examinations. It is therefore both convenient and advisable to perform a vertebral coaxial biopsy in all patients undergoing a PVP.


Subject(s)
Biopsy, Needle/methods , Fractures, Compression/pathology , Fractures, Compression/surgery , Osteoporotic Fractures/pathology , Osteoporotic Fractures/surgery , Spinal Fractures/pathology , Spinal Fractures/surgery , Vertebroplasty/methods , Aged , Aged, 80 and over , Biopsy, Needle/instrumentation , Female , Humans , Male , Middle Aged , Radiography, Interventional , Retrospective Studies , Tomography, X-Ray Computed , Vertebroplasty/instrumentation
8.
Oncogene ; 28(40): 3551-62, 2009 Oct 08.
Article in English | MEDLINE | ID: mdl-19668227

ABSTRACT

Microtubule-perturbing drugs have become front-line chemotherapeutics, inducing cell-cycle crisis as a major mechanism of action. However, these agents show pleiotropic effects on cells and can induce apoptosis through other means. Paclitaxel, a microtubule-stabilizing agent, induces a caspase-dependent apoptosis, although the precise mechanism(s) remain unclear. Here, we used genetic approaches to evaluate the role of caspase 8 in paclitaxel-mediated apoptosis. We observed that caspase 8-expressing cells are more sensitive to paclitaxel than caspase 8-deficient cells. Mechanistically, caspase 8 was found associated with microtubules, and this interaction increased after paclitaxel treatment. The prodomains death effector domains (DEDs) of caspase 8 were sufficient for interaction with microtubules, but the caspase 8 holoprotein was required for apoptosis. DED-only forms of caspase 8 were found in both primary and tumor cell lines, associating with perinuclear microtubules and the centrosome. Microtubule association, and paclitaxel sensitivity, depends on a critical lysine (K156) within a microtubule-binding motif (KLD) in DED-b of caspase 8. The results show an unexpected pathway of apoptosis mediated by caspase 8.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Caspase 8/physiology , Microtubules/physiology , Neuroblastoma/drug therapy , Paclitaxel/pharmacology , Caspase 8/chemistry , Cell Line, Tumor , Centrosome/physiology , Humans , Neuroblastoma/pathology , Protein Structure, Tertiary
9.
Radiol Med ; 114(4): 595-607, 2009 Jun.
Article in English, Italian | MEDLINE | ID: mdl-19444592

ABSTRACT

PURPOSE: The purpose of this study was to compare exposure of patient and operator to ionising radiation during percutaneous vertebroplasty performed under combined computed tomography (CT) and fluoroscopic guidance or fluoroscopic guidance alone. MATERIALS AND METHODS: With the collaboration of our physics department, we measured exposure on ten patients undergoing vertebroplasty with combined CT and fluoroscopic guidance and on ten undergoing vertebroplasty with fluoroscopic guidance alone. RESULTS: Mean operator dose was approximately 0.8 microSv during vertebroplasty done with combined CT and fluoroscopic guidance and 5.8 microSv in procedures with fluoroscopic guidance alone. Mean patient dose was approximately 6 mSv for combined guidance and 8 mSv for fluoroscopic guidance, a difference that was not found to be statistically significant. CONCLUSIONS: Although combined CT and fluoroscopic guidance is normally preferred for difficult areas such as the cervical and upper thoracic vertebrae, to ensure operator radiation protection, the technique should also be considered for areas normally treated under fluoroscopic guidance alone. However, a larger patient series is needed to correctly evaluate the real contribution of low-dose CT to patient exposure.


Subject(s)
Fluoroscopy/adverse effects , Occupational Exposure/analysis , Radiation Monitoring/methods , Radiography, Interventional/methods , Vertebroplasty/methods , Algorithms , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Fluoroscopy/methods , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Occupational Exposure/prevention & control , Radiation Dosage , Radiation, Ionizing , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery
10.
Radiol Med ; 113(1): 101-13, 2008 Feb.
Article in English, Italian | MEDLINE | ID: mdl-18338131

ABSTRACT

PURPOSE: This article reports on our experience treating vertebral fractures with percutaneous vertebroplasty. A clinical and imaging follow-up designed to identify the early (especially pulmonary embolism of bone cement) and late complications of the technique is proposed. MATERIAL AND METHODS: On the basis of the current guidelines, 101 patients were selected: 64 osteoporotic and 37 neoplastic. A total of 173 vertebrae were treated. Procedures were performed with both computed tomography and fluoroscopic guidance. Residual pain was evaluated with a visual analogue scale score immediately after vertebroplasty and 1, 15, 30, 90, 180 and 270 days later. Spine and chest radiographs were obtained 24 h after vertebroplasty; spine radiography was repeated 30 days later. RESULTS: Therapeutic success was obtained in 88% of osteoporotic patients and in 84% of neoplastic patients. Pulmonary cement emboli were identified in four patients, all of whom were asymptomatic. CONCLUSIONS: Percutaneous vertebroplasty is a safe and effective technique for the treatment of osteoporotic and neoplastic vertebral fractures. Clinical and imaging followup allows effective patient monitoring and early detection of possible complications.


Subject(s)
Spinal Fractures/surgery , Vertebroplasty/methods , Adult , Aged , Aged, 80 and over , Bone Cements/adverse effects , Female , Fluoroscopy/methods , Follow-Up Studies , Fractures, Spontaneous/surgery , Humans , Lumbar Vertebrae/surgery , Male , Middle Aged , Osteoporosis/surgery , Pain Measurement , Pain, Postoperative/etiology , Postoperative Complications/diagnosis , Pulmonary Embolism/diagnostic imaging , Radiography, Interventional/methods , Spinal Diseases/surgery , Spinal Neoplasms/surgery , Thoracic Vertebrae/surgery , Tomography, X-Ray Computed/methods , Treatment Outcome
11.
Radiol Med ; 109(1-2): 118-24, 2005.
Article in English, Italian | MEDLINE | ID: mdl-15729192

ABSTRACT

PURPOSE: The aim of this study is to assess the effectiveness and safety of the use of Vasoseal ES collagen plug in heavily anticoagulated patients with high risk of complications at the vascular access site who had undergone vascular radiological intervention. MATERIALS AND METHODS: Between January 2002 and March 2003 180 consecutive transfemoral arterial accesses in 169 patients subjected to vascular radiological procedures were performed (bilateral access was performed in 11 patients): 140 percutaneous transluminal angioplasties and 40 transarterial chemoembolisations. All the patients who underwent angioplasty were given 3,000 IU of sodic heparin intravenously during the procedure and later a prolonged antiaggregant therapy was undertaken (ticlopidine 500 mg/day and aspirin 150 mg/day). The sheaths were removed at the end of the surgical manoeuvre and two cartridges of collagen were positioned on the external surface of the artery. The mean values of platelets and partial thromboplastin time were 42,000/ml and 170 s, respectively, in cirrhotic patients against 250,000/ml and 200 s in patients with peripheral arteriopathy. The next day a colour Doppler examination was performed at the puncture site. RESULTS: The technique proved successful in 89.4% of cases (161/180). In 19/180 vascular accesses placement of the haemostatic cartridges was not possible owing to the inability to compress the common femoral artery proximal to the release site (4/19), owing to a pre-existing haematoma (5/19) and owing to the limited presence of subcutaneous tissue (10/19). The mean time required for the placement of Vasoseal ES was 4 min. The mean time-to-haemostasis was 6 min. The mean time-to-mobilisation was 4 hr. Only in two patients was there an onset of a pseudoaneurysm of the right common femoral artery; the lesions were treated with ultrasonography -guided compression. In addition, 16 small local haematomas were recorded. In 4 cases early re-puncture of the femoral artery was performed (24-48 hr following the use of the device) without consequences. CONCLUSIONS: Vasoseal ES is a safe collagen closure device characterised by a high success rate. In anticoagulated patients the device can reduce the time-to-mobilisation and the incidence of complications.


Subject(s)
Catheterization, Peripheral , Femoral Artery , Hemostatic Techniques/instrumentation , Adult , Aged , Aged, 80 and over , Catheterization, Peripheral/adverse effects , Collagen/administration & dosage , Female , Hemostatic Techniques/adverse effects , Humans , Male , Middle Aged
12.
Invest Ophthalmol Vis Sci ; 42(13): 3349-56, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11726644

ABSTRACT

PURPOSE: To evaluate the optical aberrations induced by LASIK refractive surgery for myopia on the anterior surface of the cornea and the entire optical system of the eye. METHODS: Total and corneal aberrations were measured in a group of 14 eyes (preoperative myopia ranging from -2.5 to -13 D) before and after LASIK surgery. Total aberrations were measured using a laser ray-tracing technique. Corneal aberrations were obtained from corneal elevation maps measured using a corneal system and custom software. Corneal and total wave aberrations were described as Zernike polynomial expansions. Root-mean-square (RMS) wavefront error was used as a global optical quality metric. RESULTS: Total and corneal aberrations (third-order and higher) showed a statistically significant increase after LASIK myopia surgery, by a factor of 1.92 (total) and 3.72 (corneal), on average. This increase was more pronounced in patients with the highest preoperative myopia. There is a good correlation (r = 0.97, P < 0.0001) between the aberrations induced in the entire optical system and those induced in the anterior corneal surface. However, the anterior corneal spherical aberration increased more than the total spherical aberration, suggesting also a change in the spherical aberration of the posterior corneal surface. Pupil centration and internal optical aberrations, which are not accounted for in corneal topography, play an important role in evaluating individual surgical outcomes. CONCLUSIONS: Because LASIK surgery induces changes in the anterior corneal surface, most changes in the total aberration pattern can be attributed to changes in the anterior corneal aberrations. However, because of individual interactions of the aberrations in the ocular components, a combination of corneal and total aberration measurements is critical to understanding individual outcomes, and by extension, to designing custom ablation algorithms. This comparison also reveals changes in the internal aberrations, consistent with the posterior corneal changes reported using scanning slit corneal topography.


Subject(s)
Corneal Topography , Eye/physiopathology , Keratomileusis, Laser In Situ , Myopia/surgery , Adult , Cornea/pathology , Cornea/physiopathology , Female , Humans , Male , Postoperative Period , Treatment Outcome
13.
Biochem Biophys Res Commun ; 288(2): 301-8, 2001 Oct 26.
Article in English | MEDLINE | ID: mdl-11606043

ABSTRACT

We investigated the role of the HIV-1 protein Tat in AIDS-associated dementia, by studying its toxicity on rat cortical and hippocampal neurons in vitro. We evaluated the involvement of astroglial cells and of caspase transduction pathway in determining Tat toxicity. Here we report that synthetic Tat(1-86) induced apoptotic death on cultured rat neurons in a time-dependent manner that was not influenced by glial coculture, and that was abolished by blocking caspase transduction pathway. A microfluorimetric analysis on the Tat excitatory properties on neurons, and its effect on intracellular calcium concentrations, revealed that Tat(1-86) induced increase in cytoplasmic free calcium concentrations in rat hippocampal and cortical neurons. This effect required extracellular calcium and was differently reduced by voltage dependent calcium channel blockers and both NMDA and non-NMDA glutamate receptors antagonists. Furthermore, we observed that Tat(1-86)-treated neurons showed increased sensitivity to the glutamate excitotoxicity. Thus, the Tat-induced neuronal injury seems to occur through a direct interaction of the protein with neurons, requires activation of caspases, and is likely to derive from Tat(1-86)-induced calcium loads and disruption of glutamatergic transmission.


Subject(s)
Apoptosis , Calcium/metabolism , Gene Products, tat/pharmacology , Homeostasis/drug effects , Neurons/drug effects , Animals , Cells, Cultured , Neurons/cytology , Neurons/metabolism , Rats , Rats, Sprague-Dawley
14.
Front Neuroendocrinol ; 22(3): 147-84, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11456467

ABSTRACT

Chemokines are a family of proteins associated with the trafficking of leukocytes in physiological immune surveillance and inflammatory cell recruitment in host defence. They are classified into four classes based on the positions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors. Besides their well-established role in the immune system, several recent reports have demonstrated that these proteins also play a role in the central nervous system (CNS). In the CNS, chemokines are constitutively expressed by microglial cells, astrocytes, and neurons, and their expression can be increased after induction with inflammatory mediators. Constitutive expression of chemokines and chemokine receptors has been observed in both developing and adult brains, and the role played by these proteins in the normal brain is the object of intense study by many research groups. Chemokines are involved in brain development and in the maintenance of normal brain homeostasis; these proteins play a role in the migration, differentiation, and proliferation of glial and neuronal cells. The chemokine stromal cell-derived factor 1 and its receptor, CXCR4, are essential for life during development, and this ligand-receptor pair has been shown to have a fundamental role in neuron migration during cerebellar formation. Chemokine and chemokine receptor expression can be increased by inflammatory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions. In the CNS, chemokines play an essential role in neuroinflammation as mediators of leukocyte infiltration. Their overexpression has been implicated in different neurological disorders, such as multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression, and acquired immunodeficiency syndrome-associated dementia. An emerging area of interest for chemokine action is represented by the communication between the neuroendocrine and the immune system. Chemokines have hormone-like actions, specifically regulating the key host physiopathological responses of fever and appetite. It is now evident that chemokines and their receptors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to neuroinflammation. These molecules constitute crucial regulators of cellular communication in physiological and developmental processes.


Subject(s)
Central Nervous System/physiology , Chemokines/physiology , Receptors, Chemokine/physiology , Animals , Central Nervous System Diseases/genetics , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/physiopathology , Humans , Neurosecretory Systems/physiology
15.
J Neurochem ; 77(5): 1226-36, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11389173

ABSTRACT

Stromal cell-derived factor-1 (SDF-1), the ligand of the CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co-receptor for HIV-1 infection. We previously demonstrated that CXCR4 and SDF-1alpha are expressed in cultured type-I cortical rat astrocytes, cortical neurones and cerebellar granule cells. Here, we investigated the possible functions of CXCR4 expressed in rat type-I cortical astrocytes and demonstrated that SDF-1alpha stimulated the proliferation of these cells in vitro. The proliferative activity induced by SDF-1alpha in astrocytes was reduced by PD98059, indicating the involvement of extracellular signal-regulated kinases (ERK1/2) in the astrocyte proliferation induced by CXCR4 stimulation. This observation was further confirmed showing that SDF-1alpha treatment selectively activated ERK1/2, but not p38 or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Moreover, both astrocyte proliferation and ERK1/2 phosphorylation, induced by SDF-1alpha, were inhibited by pertussis toxin (PTX) and wortmannin treatment indicating the involvement of a PTX sensitive G-protein and of phosphatidyl inositol-3 kinase in the signalling of SDF-1alpha. In addition, Pyk2 activation represent an upstream components for the CXCR4 signalling to ERK1/2 in astrocytes. To our knowledge, this is the first report demonstrating a proliferative effect for SDF-1alpha in primary cultures of rat type-I astrocytes, and showing that the activation of ERK1/2 is responsible for this effect. These data suggest that CXCR4/SDF-1 should play an important role in physiological and pathological glial proliferation, such as brain development, reactive gliosis and brain tumour formation.


Subject(s)
Astrocytes/drug effects , Chemokines, CXC/pharmacology , Receptors, CXCR4/drug effects , Signal Transduction/drug effects , Animals , Blotting, Western , Calcium/metabolism , Cell Division/drug effects , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Chemokine CXCL12 , DNA/biosynthesis , Indicators and Reagents , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Rats , Receptors, CXCR4/metabolism , Thymidine/metabolism
16.
Invest Ophthalmol Vis Sci ; 42(6): 1396-403, 2001 May.
Article in English | MEDLINE | ID: mdl-11328757

ABSTRACT

PURPOSE: To determine objectively the changes in the ocular aberrations (3rd order and above) induced by myopic LASIK refractive surgery and its impact on image quality. METHODS: The ocular aberrations of 22 normal myopic eyes (preoperative refraction ranged from -13 to -2 D) were measured before (2.9 +/- 4.3 weeks) and after (7.7 +/- 3.2 weeks) LASIK refractive surgery using a laser ray tracing technique. A set of laser pencils is sequentially delivered onto the eye through different pupil locations. For each ray, the corresponding retinal image is collected on a CCD camera. The displacement of the image centroid with respect to a reference provides direct information of the ocular aberrations. Root-mean-square (RMS) wavefront error was taken as image quality metric. RESULTS: RMS wavefront error increased significantly in all eyes but two after surgery. On average, LASIK induced a significant (P = 0.0003) 1.9-fold increase in the RMS error for a 6.5-mm pupil. The main contribution was due to the increase (fourfold, P < 0.0001) of spherical aberration. The increase in the RMS for a 3-mm pupil (1.7-fold) was also significant (P = 0.02). The modulation transfer (computed for 6.5-mm pupil) decreased on average by a factor of 2 for middle-high spatial frequencies. CONCLUSIONS: (1) Laser ray tracing is a well-suited, robust, and reliable technique for the evaluation of the change of ocular aberrations with refractive surgery. (2) Refractive surgery induces important amounts of 3rd and higher order aberrations. The largest increase occurs for spherical aberration. Decentration of the ablation pattern seems to generate 3rd order aberrations. (3) This result is important for the design of customized ablation algorithms, which should cancel existing preoperative aberrations while avoiding the generation of new aberrations.


Subject(s)
Cornea/surgery , Keratomileusis, Laser In Situ , Myopia/surgery , Ocular Physiological Phenomena , Vision, Ocular/physiology , Adult , Female , Humans , Lasers , Male , Psychophysics , Pupil/physiology , Retina/physiology
17.
Brain Res Brain Res Protoc ; 5(3): 273-81, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10906493

ABSTRACT

Ciliary neurotrophic factor (CNTF) promotes the survival of several populations of neurons, including sensory and motor neurons. It is mainly produced by Schwann cells and astrocytes and exerts its biological function via a specific membrane receptor. We recently determined the nuclear localization of CNTF in producing cells, after transfection and in the heterologous system of Xenopus oocytes. In the present paper, we describe in detail the techniques for the detection of CNTF in the nucleus of rat astrocytes, transfected cells, isolated nuclei and injected Xenopus oocytes.


Subject(s)
Astrocytes/chemistry , Cell Nucleus/chemistry , Ciliary Neurotrophic Factor/analysis , Fluorescent Antibody Technique, Indirect , Transfection/methods , Animals , Antibodies, Monoclonal , COS Cells , Ciliary Neurotrophic Factor/immunology , Female , Glioma , Microinjections , Microscopy, Confocal/methods , Oocytes/physiology , Precipitin Tests/methods , RNA, Messenger , Rats , Rats, Sprague-Dawley , Tumor Cells, Cultured , Xenopus laevis
18.
J Neurochem ; 73(6): 2348-57, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10582593

ABSTRACT

Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell-derived factor 1, (SDF1), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and acts to modulate cell migration, differentiation, and proliferation. CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down-regulation of CXCR4, whereas treatment with phorbol esters did not affect SDF1 expression and down-modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1alpha (hSDF1alpha) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1alpha with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.


Subject(s)
AIDS Dementia Complex/metabolism , Astrocytes/metabolism , Calcium Signaling/drug effects , Chemokines, CXC/biosynthesis , HIV-1/physiology , Nerve Tissue Proteins/biosynthesis , Neuroglia/metabolism , Neurons/metabolism , Receptors, CXCR4/biosynthesis , Animals , Blotting, Northern , Blotting, Western , COS Cells , Cells, Cultured , Cerebellum/cytology , Cerebral Cortex/cytology , Chemokine CXCL12 , Chemokines, CXC/genetics , Chlorocebus aethiops , Colforsin/pharmacology , Cyclic AMP/biosynthesis , Fluorescent Antibody Technique, Indirect , GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors , GTP-Binding Protein alpha Subunits, Gi-Go/physiology , Gene Expression Regulation , HIV Envelope Protein gp120/pharmacology , Humans , Ligands , Lipopolysaccharides/pharmacology , Nerve Tissue Proteins/genetics , Organ Specificity , Rats , Rats, Sprague-Dawley , Receptors, CXCR4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Second Messenger Systems/drug effects , Virulence Factors, Bordetella/pharmacology
20.
Ann N Y Acad Sci ; 876: 201-9, 1999 Jun 22.
Article in English | MEDLINE | ID: mdl-10415611

ABSTRACT

Human immunodeficiency virus (HIV-1) infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults called AIDS dementia complex. Evidence from in vitro and in vivo studies suggests a role for the viral envelope glycoprotein gp120, as a mediator of neurotoxicity. However, the site of interaction of gp120 with neurons and astrocytes to mediate neuronal death is still unknown. Recently the chemokine receptors, CCR5 and CXCR4, have been identified as co-receptors together with CD4 for HIV-1 entry into the target cells, suggesting a possible role for these receptors in the pathogenesis of the HIV-1 infection in the brain. Here we report the expression of CCR5 and CXCR4 in many different rat brain areas. We also found both receptors in cultured type I astrocytes demonstrating that glial cells may represent an important target for chemokines in vivo. Indeed, the functional capacity of CXCR4 receptor in astrocytes was demonstrated showing that SDF 1 alpha induced an increase of intracellular calcium concentration.


Subject(s)
Brain/metabolism , Receptors, Chemokine/metabolism , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Calcium/metabolism , Cells, Cultured , Chemokine CXCL12 , Chemokines, CXC/pharmacology , Fluorescent Antibody Technique , Rats , Rats, Sprague-Dawley , Receptors, CCR5/metabolism , Receptors, CXCR4/metabolism
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