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1.
Eur J Nucl Med Mol Imaging ; 48(1): 40-52, 2021 01.
Article in English | MEDLINE | ID: mdl-32378022

ABSTRACT

PURPOSE: To evaluate the feasibility and sensitivity of multimodality PET/CT and MRI imaging for non-invasive characterization of brain microglial/macrophage activation occurring during the acute phase in a mouse model of relapsing remitting multiple sclerosis (RR-MS) using [18F]DPA-714, a selective radioligand for the 18-kDa translocator protein (TSPO), superparamagnetic iron oxide particles (SPIO), and ex vivo immunohistochemistry. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in female SJL/J mice by immunization with PLP139-151. Seven symptomatic EAE mice and five controls underwent both PET/CT and MRI studies between 11 and 14 days post-immunization. SPIO was injected i.v. in the same animals immediately after [18F]DPA-714 and MRI acquisition was performed after 24 h. Regional brain volumes were defined according to a mouse brain atlas on co-registered PET and SPIO-MRI images. [18F]DPA-714 standardized uptake value (SUV) ratios (SUVR), with unaffected neocortex as reference, and SPIO fractional volumes (SPIO-Vol) were generated. Both SUVR and SPIO-Vol values were correlated with the clinical score (CS) and among them. Five EAE and four control mice underwent immunohistochemical analysis with the aim of identifying activated microglia/macrophage and TSPO expressions. RESULTS: SUVR and SPIO-Vol values were significantly increased in EAE compared with controls in the hippocampus (p < 0.01; p < 0.02, respectively), thalamus (p < 0.02; p < 0.05, respectively), and cerebellum and brainstem (p < 0.02), while only SPIO-Vol was significantly increased in the caudate/putamen (p < 0.05). Both SUVR and SPIO-Vol values were positively significantly correlated with CS and among them in the same regions. TSPO/Iba1 and F4/80/Prussian blue staining immunohistochemistry suggests that increased activated microglia/macrophages underlay TSPO expression and SPIO uptake in symptomatic EAE mice. CONCLUSIONS: These preliminary results suggest that both activated microglia and infiltrated macrophages are present in vulnerable brain regions during the acute phase of PLP-EAE and contribute to disease severity. Both [18F]DPA-714-PET and SPIO-MRI appear suitable modalities for preclinical study of neuroinflammation in MS mice models.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Animals , Encephalomyelitis, Autoimmune, Experimental/diagnostic imaging , Female , Macrophage Activation , Macrophages , Magnetic Resonance Imaging , Mice , Microglia , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Pyrazoles , Pyrimidines
2.
Sci Rep ; 9(1): 4208, 2019 03 12.
Article in English | MEDLINE | ID: mdl-30862866

ABSTRACT

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro, and of B cells before and after six months of GA administration in vivo. Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca2+ homeostasis in these cells.


Subject(s)
B-Lymphocytes/metabolism , Gene Expression Regulation/drug effects , Glatiramer Acetate/administration & dosage , Homeostasis/drug effects , Ion Channels/biosynthesis , Multiple Sclerosis, Relapsing-Remitting/metabolism , B-Lymphocytes/pathology , Calcium/metabolism , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/pathology , Female , Humans , Male , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/pathology
3.
Cell Death Differ ; 19(4): 562-72, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21959935

ABSTRACT

Changes in intracellular [Ca(2+)](i) levels have been shown to influence developmental processes that accompany the transition of human oligodendrocyte precursor cells (OPCs) into mature myelinating oligodendrocytes and are required for the initiation of the myelination and re-myelination processes. In the present study, we explored whether calcium signals mediated by the selective sodium calcium exchanger (NCX) family members NCX1, NCX2, and NCX3, play a role in oligodendrocyte maturation. Functional studies, as well as mRNA and protein expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently modulated during OPC differentiation into oligodendrocyte phenotype. In fact, whereas NCX1 was downregulated, NCX3 was strongly upregulated during oligodendrocyte development. The importance of calcium signaling mediated by NCX3 during oligodendrocyte maturation was supported by several findings. Indeed, whereas knocking down the NCX3 isoform in OPCs prevented the upregulation of the myelin protein markers 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) and myelin basic protein (MBP), its overexpression induced an upregulation of CNPase and MBP. Furthermore, NCX3-knockout mice showed not only a reduced size of spinal cord but also marked hypo-myelination, as revealed by decrease in MBP expression and by an accompanying increase in OPC number. Collectively, our findings indicate that calcium signaling mediated by NCX3 has a crucial role in oligodendrocyte maturation and myelin formation.


Subject(s)
Calcium Signaling/physiology , Cell Differentiation/physiology , Nerve Tissue Proteins/biosynthesis , Neural Stem Cells/metabolism , Oligodendroglia/metabolism , Sodium-Calcium Exchanger/biosynthesis , Animals , Cell Line , Gene Expression Regulation/physiology , Gene Silencing , Humans , Mice , Mice, Knockout , Myelin Sheath/genetics , Myelin Sheath/metabolism , Nerve Tissue Proteins/genetics , Neural Stem Cells/cytology , Oligodendroglia/cytology , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Sodium-Calcium Exchanger/genetics
4.
Minerva Ginecol ; 61(1): 1-12, 2009 Feb.
Article in Italian | MEDLINE | ID: mdl-19204656

ABSTRACT

AIM: The aim of this study was to evaluate if the surgical approach without pelvic lymphadenectomy and with adjuvant radiotherapy in the patients suffering from endometrioid adenocarcinoma type at high risk (of lymphatic metastasis) in early stage can be substituted by only surgery with pelvic lymphadenectomy (with or without para-aortic lymphadenectomy). METHODS: A retrospective study was carried out on 56 patients who underwent surgery with eventual adjuvant radiotherapy and were attended during the follow-up in the Operative Unit of Gynecology and Obstetrics from 1997 to 2004. The patients were divided into two groups: the low risk group and the high risk group. The cancer grading (G) was defined before the surgery with an hystological exam on endometrial biopsies. The follow-up had a medium duration of 30 months (range: 9-44 months) and consisted of the evaluation of: cancer related survival (CRS); recurrence free survival (RFS). Both were evaluated according to age, risk type, and therapy adopted. RESULTS: Four patients (7.1%) showed relapse during the period of study in a medium time of 24 months (range: 12-36): 2 of these patients (C and D cases; 36%) had a relapse both locally (pelvic wall) and distantly; the other two (A and B cases; 36%) had only a distant relapse. None of the patients at the stage IA had a relapse, but it occurred in the 8.7% of the cases (N.=2) IB and in the 10.5 % of the patients IC (N.=2). One patient of the low risk group (3.8%) (case A) had a distant relapse (lungs) 12 months after the surgery and died 6 months after the appearance of the relapse without any additional treatment, because of age and of concomitant pathologies which suggested another illness. Three patients of the high risk group (10%) had a local and /or distant relapse (one only distant, two both distant and local). One of them with distant relapse (36 months after the primary treatment) (case B) is still alive, even though she has got a controlled cancer, 8 months after the rescue treatment (chemotherapy), whereas two of them died in a medium time of 14 months (range 13-15 months) from the rescue treatment (C and D cases). One of the three patients of the high risk group underwent the standard surgical treatment with lympho-adenectomy (case B) whereas the other two underwent the standard surgical treatment with aiding radiotherapy (C and D cases). The CRS and the RFS were 96.2% and 96.2% in the low risk group, 93.3% and 90% in the high risk group, respectively. CONCLUSIONS: The standard surgery offers a good prognosis to the low risk group patients. To the high risk group the CRS and the RFS were better with standard surgery with lymphadenectomy than with standard surgery with adjuvant radiotherapy. The degree of differentiation of the cancer is the most important prognostic factor in relation to the survival free from relapse (RFS).


Subject(s)
Carcinoma, Endometrioid/radiotherapy , Carcinoma, Endometrioid/surgery , Endometrial Neoplasms/radiotherapy , Endometrial Neoplasms/surgery , Lymph Node Excision , Neoplasm Recurrence, Local , Aged , Aged, 80 and over , Biopsy , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Early Detection of Cancer , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Hysterectomy , Lymphatic Metastasis/prevention & control , Middle Aged , Neoplasm Staging , Pelvis , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis , Treatment Outcome
5.
Eur J Ophthalmol ; 19(1): 154-8, 2009.
Article in English | MEDLINE | ID: mdl-19123167

ABSTRACT

PURPOSE: To describe anatomic and functional outcomes in two patients with long-standing severe chronic central serous chorioretinopathy (CSC) with foveal and gravitational atrophy treated with low-fluence photodynamic therapy (PDT). METHODS: Two patients with a history of over 10 years of chronic CSC and development of gravitational tracts, with best-corrected visual acuity

Subject(s)
Fovea Centralis/pathology , Photochemotherapy , Retinal Diseases/drug therapy , Atrophy , Chronic Disease , Coloring Agents , Fluorescein Angiography , Humans , Indocyanine Green , Male , Middle Aged , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Retinal Diseases/diagnosis , Retinal Diseases/physiopathology , Retinal Pigment Epithelium/pathology , Serum , Verteporfin , Visual Acuity/physiology , Visual Field Tests , Visual Fields/physiology
7.
Mol Pharmacol ; 72(3): 665-73, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17495071

ABSTRACT

The aim of the present study was to investigate whether K(V)3.4 channel subunits are involved in neuronal death induced by neurotoxic beta-amyloid peptides (Abeta). In particular, to test this hypothesis, three main questions were addressed: 1) whether the Abeta peptide can up-regulate both the transcription/translation and activity of K(V)3.4 channel subunit and its accessory subunit, MinK-related peptide 2 (MIRP2); 2) whether the increase in K(V)3.4 expression and activity can be mediated by the nuclear factor-kappaB (NF-kappaB) family of transcriptional factors; and 3) whether the specific inhibition of K(V)3.4 channel subunit reverts the Abeta peptide-induced neurodegeneration in hippocampal neurons and nerve growth factor (NGF)-differentiated PC-12 cells. We found that Abeta(1-42) treatment induced an increase in K(V)3.4 and MIRP2 transcripts and proteins, detected by reverse transcription-polymerase chain reaction and Western blot analysis, respectively, in NGF-differentiated PC-12 cells and hippocampal neurons. Patch-clamp experiments performed in whole-cell configuration revealed that the Abeta peptide caused an increase in I(A) current amplitude carried by K(V)3.4 channel subunits, as revealed by their specific blockade with blood depressing substance-I (BDS-I) in both hippocampal neurons and NGF-differentiated PC-12 cells. The inhibition of NF-kappaB nuclear translocation with the cell membrane-permeable peptide SN-50 prevented the increase in K(V)3.4 protein and transcript expression. In addition, the SN-50 peptide was able to block Abeta(1-42)-induced increase in K(V)3.4 K(+) currents and to prevent cell death caused by Abeta(1-42) exposure. Finally, BDS-I produced a similar neuroprotective effect by inhibiting the increase in K(V)3.4 expression. As a whole, our data indicate that K(V)3.4 channels could be a novel target for Alzheimer's disease pharmacological therapy.


Subject(s)
Amyloid beta-Peptides/toxicity , Apoptosis/drug effects , Neurons/drug effects , Peptide Fragments/toxicity , Peptides/metabolism , Shaw Potassium Channels/metabolism , Up-Regulation/drug effects , Amyloid beta-Peptides/chemistry , Animals , Cell Death/drug effects , Cells, Cultured , Cnidarian Venoms/pharmacology , Electrophysiology , Hippocampus/cytology , Hippocampus/embryology , NF-kappa B/antagonists & inhibitors , Neurons/cytology , Neurons/physiology , PC12 Cells , Patch-Clamp Techniques , Peptide Fragments/chemistry , Peptides/genetics , Peptides/pharmacology , RNA, Messenger/analysis , Rats , Rats, Wistar , Sea Anemones/chemistry , Shaw Potassium Channels/genetics
8.
Ann N Y Acad Sci ; 1099: 413-26, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17446481

ABSTRACT

Over the last few years, although extensive studies have focused on the relevant function played by the sodium-calcium exchanger (NCX) during focal ischemia, a thorough understanding of its role still remains a controversial issue. We explored the consequences of the pharmacological inhibition of this antiporter with conventional pharmacological approach, with the synthetic inhibitory peptide, XIP, or with an antisense strategy on the extent of brain damage induced by the permanent occlusion of middle cerebral artery (pMCAO) in rats. Collectively, the results of these studies suggest that ncx1 and ncx3 genes could be play a major role to limit the severity of ischemic damage probably as they act to dampen [Na+]i and [Ca2+]i overload. This mechanism seems to be normally activated in the ischemic brain as we found a selective upregulation of NCX1 and NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive proteolytic degradation in the ipsilateral cerebral hemisphere. All together these results suggest that a rescue program centered on an increase NCX function and expression could halt the progression of the ischemic damage. On the basis of this evidence we directed our attention to the understanding of the transductional and transcriptional pathways responsible for NCX upregulation. To this aim, we are studying whether the brain isoform of Akt, Akt1, which is a downstream effector of neurotrophic factors, such as NGF can, in addition to affecting the other prosurvival cascades, also exert its neuroprotective effect by modulating the expression and activity of ncx1, ncx2, and ncx3 gene products.


Subject(s)
Brain Ischemia/metabolism , Brain/metabolism , Cell Hypoxia , Neurons/metabolism , Sodium-Calcium Exchanger/genetics , Animals , Base Sequence , RNA, Messenger/genetics , Rats , Sodium-Calcium Exchanger/drug effects
9.
Eur J Ophthalmol ; 15(4): 513-6, 2005.
Article in English | MEDLINE | ID: mdl-16001389

ABSTRACT

PURPOSE: Neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) has a poor natural history and the efficacy of any treatment has not yet been established. The authors describe a combined surgical treatment. METHODS: A 76-year-old woman presented with a best-corrected visual acuity (BCVA) of 20/600 in the right eye and macula with stage 3 RAP as identified by fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). After a standard three-port pars plana core vitrectomy (PPV), endodiathermy of the arteriolar and venous feeder vessels of each lesion was performed, intraretinal RAP feeder vessels were cut with manual vertical intraocular scissors, and 0.1 mL of triamcinolone acetonide (TAAC) was injected intravitreally. At 1 and 4 weeks and at the sixth month, the patient underwent a complete eye examination, FA, ICGA, and OCT to assess outcomes and complications. RESULTS: Six months later, BCVA was stable at 20/300, intraocular pressure was 15 mmHg, anterior segment and vitreous cavity were clear without evidence of TAAC granules, and retina was attached. FA and ICGA showed a complete occlusion of the RAP and absence of leakage or ischemia and OCT demonstrated decreased macular thickness with resolution of both intraretinal edema and pigment epithelium detachment, and the restoration of the normal macular profile. At the end of follow-up, the authors did not observe any ocular or systemic complication. CONCLUSIONS: Surgical approach to RAP stage 3 with intravitreal injection of 4 mg of TAAC was safe and anatomically effective.


Subject(s)
Angiomatosis/therapy , Diathermy , Glucocorticoids/therapeutic use , Macular Degeneration/therapy , Retinal Neovascularization/therapy , Triamcinolone Acetonide/therapeutic use , Vitrectomy , Aged , Angiomatosis/drug therapy , Angiomatosis/surgery , Combined Modality Therapy , Female , Fluorescein Angiography , Humans , Indocyanine Green , Intraocular Pressure , Macular Degeneration/drug therapy , Macular Degeneration/surgery , Retinal Artery/drug effects , Retinal Artery/surgery , Retinal Neovascularization/drug therapy , Retinal Neovascularization/surgery , Retinal Vessels/drug effects , Retinal Vessels/surgery , Tomography, Optical Coherence , Visual Acuity
10.
Minerva Ginecol ; 57(2): 189-98, 2005 Apr.
Article in Italian | MEDLINE | ID: mdl-15940081

ABSTRACT

AIM: The aim of the study was to 1) evaluate the gestational age at diagnosis and the incidence of single umbilical artery in an unselected population of 3750 pregnant women; 2) identify its association with malformations and/or karyotype aberrations in pre/postnatal age; 3) evaluate the fetal-neonatal outcome; 4) investigate the likelihood that a fetus might be affected by a cytogenetic abnormality even in presence of an apparently ''isolated'' single umbilical artery. METHODS: Transabdominal ultrasound of the umbilical vessels and histological confirmation at birth. In presence of single umbilical artery an accurate prenatal ultrasound assessment, karyotyping (pre/postnatal), and clinical follow-up after birth were performed. RESULTS: The incidence of single umbilical artery in our population resulted 1.07% (40/3750), being ''isolated'' in 40% of cases. The diagnosis of chromosomal aberration associated with single umbilical artery was made in 6 cases (15%), while structural fetal abnormalities in absence of causal chromosomal anomalies were present in 9 cases (22.5%), with syndromic patterns in 3 of them. In 2 cases with chromosomal anomalies the single umbilical artery was apparently ''isolated'' at the ultrasound examination between the 17th and the 22nd week of gestation. Excluding 4 terminations of pregnancy, the perinatal mortality percentage resulted 25% (9/36); similarly, fetal growth retardation was present in 25% of cases (9/36). CONCLUSIONS: The incidence of single umbilical artery in our population confirms that this fetal vascular anomaly is frequently identified in pregnancy. In the light of our cases and data in the literature it is evident that diligent surveillance in prenatal age and accurate clinical follow-up after birth are mandatory when a single umbilical artery has been diagnosed. Finally, the possibility, even if rare, that even when the single umbilical artery is apparently ''isolated'', a chromosomal aberration might be present (1/24 of our ''isolated'' cases) should be considered when addressing correct counselling to the couples.


Subject(s)
Infant, Newborn, Diseases/diagnostic imaging , Infant, Newborn, Diseases/epidemiology , Umbilical Arteries , Chromosome Aberrations , Gestational Age , Humans , Incidence , Infant, Newborn , Infant, Newborn, Diseases/mortality , Prenatal Diagnosis , Ultrasonography , Umbilical Arteries/abnormalities , Umbilical Arteries/cytology , Umbilical Arteries/diagnostic imaging
11.
Retina ; 25(4): 438-42, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15933589

ABSTRACT

PURPOSE: To report five cases of classic choroidal neovascularization (CNV) associated with choroidal nevus treated with photodynamic therapy (PDT) with verteporfin. METHODS: The patients underwent an ophthalmologic evaluation, including fluorescein angiography and indocyanine green angiography. Clinical and angiographic data were retrospectively analyzed to evaluate visual acuity outcomes and both clinical evolution and angiographic evolution. RESULTS: Two patients presented with subfoveal CNV, and three had juxtafoveal CNV. The mean follow-up was 25.8 months. Visual outcomes were extremely variable. Indeed, best-corrected visual acuity decreased in three eyes, stabilized in one case, and improved in the other case. The number of PDT sessions necessary to obtain CNV stabilization with cessation of fluorescein leakage varied from one to six. CONCLUSION: Bearing in mind that both the natural history and the post-PDT outcome may be extremely variable, further studies are needed to assess the real benefit of PDT for classic CNV secondary to choroidal nevus.


Subject(s)
Choroid Neoplasms/complications , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/etiology , Nevus, Pigmented/complications , Photochemotherapy , Aged , Capillary Permeability , Choroid Neoplasms/diagnosis , Choroid Neoplasms/drug therapy , Choroidal Neovascularization/diagnosis , Coloring Agents , Female , Fluorescein Angiography , Humans , Indocyanine Green , Male , Middle Aged , Nevus, Pigmented/diagnosis , Nevus, Pigmented/drug therapy , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Retreatment , Retrospective Studies , Verteporfin , Visual Acuity
12.
Eur J Ophthalmol ; 15(1): 89-95, 2005.
Article in English | MEDLINE | ID: mdl-15751245

ABSTRACT

PURPOSE: To evaluate safety and efficacy of intravitreal triamcinolone acetonide (TAAC) injections in the treatment of refractory pseudophakic cystoid macular edema (CME). METHODS: Seven eyes of six patients (age range: 50-74) with pseudophakic CME resistant to standard treatment received intravitreal injections of 4 mg of TAAC with all vehicle. Mean preinjection duration of CME was 18.3 months. A mean of 2.1+/-1.2 (range 1 to 4) treatments were performed in four eyes (57.1 %) when visual acuity deteriorated towards baseline levels. Visual acuity assessment, optical coherence tomography (OCT), and fluorescein angiography (FFA) were performed pre- and postoperatively to evaluate results of TAAC injections. Intraocular pressure (IOP) and complications related to treatment were assessed. RESULTS: After 11.1+/-3.9 months, mean best-corrected visual acuity (BCVA) increased (p =0.019) from 20/132 to a best value of 20/38. Mean macular thickness decreased from 517.29+/-146.98 mm to a best value of 263.71+/-83.13 mm (p=0.0018). Area of fluorescein leakage decreased (p<0.0001) from 11.84+/-0.93 mm2 at baseline to a minimal value of 3.86+/-0.98 mm2. The anatomic and functional improvement appeared after 1 month from the intravitreal injection and persisted through at least 3 months of follow-up. At the end of follow-up BCVA, macular thickness, and area of fluorescein leakage did not differ from baseline. Four eyes (57.1 %) developed IOP values higher than 21 mmHg, controlled by topical treatment. Two patients developed an endophthalmitis-like reaction. CONCLUSIONS: Intravitreal TAAC was relatively safe and effective in resistant cases of pseudophakic CME with a temporary beneficial effect on visual acuity and macular edema.


Subject(s)
Glucocorticoids/therapeutic use , Macular Edema/drug therapy , Pseudophakia/drug therapy , Triamcinolone Acetonide/therapeutic use , Aged , Fluorescein Angiography , Humans , Injections , Intraocular Pressure , Macular Edema/etiology , Macular Edema/physiopathology , Male , Middle Aged , Pilot Projects , Pseudophakia/complications , Pseudophakia/physiopathology , Safety , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity , Vitreous Body
13.
Eur J Neurosci ; 20(2): 441-58, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15233753

ABSTRACT

Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca(2+) (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB(1) cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism.


Subject(s)
Amidohydrolases/metabolism , Amygdala/enzymology , Cerebellum/enzymology , Hippocampus/enzymology , Monoacylglycerol Lipases/metabolism , Presynaptic Terminals/enzymology , Synapses/enzymology , Amidohydrolases/genetics , Amygdala/ultrastructure , Animals , Calbindin 2 , Calbindins , Cerebellum/ultrastructure , Cholecystokinin/metabolism , Fluorescent Antibody Technique/methods , Glutamate Decarboxylase/metabolism , Hippocampus/ultrastructure , Isoenzymes/metabolism , Male , Mice , Mice, Knockout , Microscopy, Immunoelectron/methods , Parvalbumins/metabolism , Rats , Rats, Wistar , S100 Calcium Binding Protein G/metabolism , Synapses/ultrastructure
14.
Eur J Ophthalmol ; 14(6): 572-4, 2004.
Article in English | MEDLINE | ID: mdl-15638111

ABSTRACT

PURPOSE: Sequential drainage of subretinal fluid (D), injection of air (A), cryotherapy (C), and application of local explants (E) (D-ACE) sequence was introduced in order to overcome the problems encountered in managing superior bullous detachments from multiple large equatorial breaks. The authors recently observed the occurrence of a full-thickness macular hole in one patient developing the day after he underwent a D-ACE procedure. METHODS: A 61-year-old man presented a bullous retinal detachment in the right eye extending from the 9:30 to the 2 o'clock position, and posteriorly to the vascular arcades two retinal tears were noted, at the equator at 11 o'clock, and anterior to the equator at 12 o'clock. The patient underwent a D-ACE procedure. Subretinal fluid was drained above the lateral rectus muscle at the equator. One and a half milliliters of air were injected 3.5 mm from the limbus midway between the superior and the medial rectus insertions. Cryotherapy was applied to the retinal breaks. A 240 encircling band was used in conjunction with a 276 tyre segment at the level of the tears. RESULTS: One day after surgery, the retina was flat, but a full-thickness macular hole could be seen with a surrounding cuff of subretinal fluid. CONCLUSIONS: The mechanisms proposed to explain the occurrence of full-thickness macular holes after D-ACE may involve the concurrence of scleral elongation and vitreofoveal traction by means of previous partial posterior vitreous detachment with persistent posterior attachments at the fovea.


Subject(s)
Ophthalmologic Surgical Procedures/adverse effects , Postoperative Complications , Retinal Detachment/surgery , Retinal Perforations/etiology , Air , Cryotherapy , Drainage/methods , Humans , Injections , Male , Middle Aged , Scleral Buckling , Visual Acuity
15.
Eur J Ophthalmol ; 13(6): 532-5, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12948310

ABSTRACT

PURPOSE: To describe a technique for suturing a luxated intraocular lens (IOL) in the vitreous cavity directly to the ciliary sulcus using intraocular slipknot without IOL extraction. DESIGN: Noncomparative interventional case series. MATERIALS AND METHODS: A three-port vitrectomy was performed in all cases. According to the Lewis procedure, two scleral flaps and relative sclerectomies were performed at 3 and 9 o'clock position. IOL was rescued from vitreous cavity by means of perfluorocarbon and stabilized in anterior chamber by intravitreal forceps. Corneal endothelium was preserved by a dispersive ophthalmic viscosurgical device coating. Double armed 10-0 polypropylene was introduced into the vitreous cavity through the 9 o'clock sclerotomy incision and both the needles were passed out of the eye by the 3-o'clock position sclerotomy, guided by a bent 27-gauge needle 1.5 mm from the limbus. Hooking the slipknot around the haptics of the IOL in the anterior chamber by means of vitreous forceps, the 10-0 polypropylene was pulled so that the IOL haptic was fixated onto the sulcus. The same procedure was used to fixate the opposite haptic to the ciliary sulcus at the opposite position. RESULTS: In all four cases, the IOL fixated stably and remained well positioned. No significant intraoperative or postoperative complications occurred. CONCLUSIONS: This technique enables secure fixation of the luxated IOL in the vitreous without extracting it.


Subject(s)
Anterior Chamber/surgery , Foreign-Body Migration/surgery , Lens Implantation, Intraocular/methods , Lenses, Intraocular , Sclera/surgery , Suture Techniques , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications , Refraction, Ocular , Treatment Outcome , Visual Acuity , Vitrectomy/methods
16.
Eur J Ophthalmol ; 13(2): 218-20, 2003 03.
Article in English | MEDLINE | ID: mdl-12696645

ABSTRACT

PURPOSE: Epiretinal membranes (ERM) are a common finding in old patients. Pars plana vitrectomy is effective for removing ERM from the macula, but some postoperative complications are relatively frequent. In the present report, we describe a 73-year-old man in whom extrafoveal choroidal neovascularization developed four months after surgery. METHODS: Choroidal neovascularization was treated by argon laser photocoagulation. RESULTS: Six months after treatment, the choroidal neovascularization was obliterated, with no recurrence of ERM. CONCLUSIONS: Choroidal neovascularization can be an unusual complication of ERM surgery, and should be suspected in case of poor visual outcome or recurrence of symptoms.


Subject(s)
Choroidal Neovascularization/etiology , Epiretinal Membrane/surgery , Vitrectomy/adverse effects , Aged , Choroidal Neovascularization/surgery , Humans , Laser Coagulation , Male , Tomography , Visual Acuity
17.
Ophthalmology ; 108(11): 2029-37, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11713074

ABSTRACT

OBJECTIVE: This study evaluated the efficacy, predictability, stability, and safety of a software program (Corneal Interactive Programmed Topographic Ablation [CIPTA], LIGI, Taranto, Italy), which, by transferring programmed ablation from the corneal topograph to a flying-spot excimer laser, provides customized laser ablation for correction of postkeratoplasty astigmatism. DESIGN: Noncomparative consecutive interventional case series. PARTICIPANTS: Ten eyes of 10 patients with a mean age of 41.4 years (range, 26-64) had CIPTA-guided photoastigmatic refractive keratectomy (PARK) at the Clinica Oculistica of Bari (Italy). Two patients were treated for hyperopic astigmatism and eight for myopic astigmatism. All the patients had irregular astigmatism after penetrating keratoplasty. OPERATION: Topography was acquired by a corneal topograph (Orbscan II, Orbtek, Inc., Salt Lake City, UT). This, together with refractive data, was processed to obtain a customized altimetric ablation profile that was transferred to a flying-spot laser (Laserscan 2000, Lasersight, Orlando, FL). MAIN OUTCOME MEASURES: Data on uncorrected (UCVA) and best-corrected (BCVA) visual acuity, predictability, stability of refraction, and any complications were analyzed. RESULTS: Mean follow-up was 8.4 months (range, 6-12; SD 2.4). At the last postoperative examination, seven eyes (70%) had a UCVA superior to 20/40. Three eyes (30%) had a UCVA of 20/20. Five eyes (50%) were within 0.50 diopters (D) of attempted correction in the spherical equivalent, and eight eyes (80%) within 1 D. Index of success of astigmatic correction was 0.19. All the eyes (100%) gained Snellen lines of BCVA. We did not observe any decentration and/or haze after PARK treatment performed in this study. CONCLUSIONS: The combination of topographic data with computer-controlled flying-spot excimer laser ablation is a suitable solution for correcting irregular astigmatism after penetrating keratoplasty.


Subject(s)
Astigmatism/surgery , Cornea/surgery , Corneal Topography , Keratoplasty, Penetrating/adverse effects , Photorefractive Keratectomy/methods , Adult , Astigmatism/etiology , Female , Follow-Up Studies , Humans , Lasers, Excimer , Male , Middle Aged , Safety , Visual Acuity
18.
Ophthalmology ; 108(9): 1695-703, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11535475

ABSTRACT

OBJECTIVE: This study evaluated the efficacy, predictability, stability, and safety of a software program (Corneal Interactive Programmed Topographic Ablation, CIPTA, LIGI, Taranto, Italy), which, by transferring programmed ablation from the corneal topograph to a flying-spot excimer laser, provides customized laser ablation for correction of postmyopic photorefractive keratectomy (PRK) decentrations. DESIGN: Noncomparative consecutive case series. PARTICIPANTS: Thirty-two eyes of 32 subjects with a mean age of 35 years (range, 19-49; standard deviation [SD], 7.9) had CIPTA-guided PRK at the Clinica Oculistica of Bari University (Italy). All the subjects had irregular astigmatism after postmyopic PRK because of clinically significant, decentered treatments of more than 1 mm. OPERATION: Individual topographies were acquired by a corneal topograph (Orbscan II, Orbtek, Inc., Salt Lake City, UT). These, together with refractive data, were processed to obtain a customized altimetric ablation profile that was transferred to a flying-spot laser (Laserscan 2000, Lasersight, Orlando, FL). MAIN OUTCOME MEASURES: The topographic study of centration and data on uncorrected (UCVA) and best-corrected (BCVA) visual acuity, predictability, and stability of refraction, and any complications, were analyzed. RESULTS: Mean follow-up was 10.3 months (range, 4-18 months; SD, 5.8). At the last postoperative examination, 29 eyes (90.6%) had a UCVA superior to 20/40. Nineteen eyes (59.4%) had a UCVA of 20/20. Twenty-two eyes (68.75%) were within 0.50 diopters (D) of attempted correction in the spherical equivalent and 28 eyes (87.5%) were within 1 D. The index of success of astigmatic correction was 0.15. No eye lost Snellen lines of BCVA, whereas 18 eyes (56.25%) gained Snellen lines. Postoperative topographies revealed well-centered treatments. CONCLUSIONS: The combination of topographic data with computer controlled flying-spot excimer laser ablation is a suitable solution for correcting irregular astigmatism after postmyopic PRK decentrations.


Subject(s)
Cornea/surgery , Corneal Topography/methods , Myopia/surgery , Photorefractive Keratectomy/methods , Adult , Astigmatism/surgery , Corneal Topography/instrumentation , Female , Follow-Up Studies , Humans , Lasers, Excimer , Male , Middle Aged , Refraction, Ocular , Reoperation , Safety , Software , Visual Acuity
20.
Ophthalmology ; 107(8): 1578-87, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10919913

ABSTRACT

OBJECTIVE: This study evaluated the efficacy, predictability, stability, and safety of a software program (Corneal Interactive Programmed Topographic Ablation (CIPTA) LIGI, Taranto, Italy) which, by transferring programmed ablation from the corneal topography to a flying-spot excimer laser, provides customized laser ablation. DESIGN: Noncomparative consecutive case series. PARTICIPANTS: Forty-two eyes of 34 subjects with a mean age of 33.9 (range, 20-54) had CIPTA at the Cattedra di Ottica Fisiopatologica of Bari (Italy). Twenty-eight eyes were treated for hyperopic astigmatism and 14 for myopic astigmatism. All the subjects had irregular astigmatism. OPERATION: Topography was acquired by a corneal topography mapping system (Orbscan, Orbtek, Inc., Salt Lake City, UT). These data were processed to obtain a customized altimetric ablation profile, which was transferred to a flying-spot laser (Laserscan 2000, Lasersight, Orlando, FL). MAIN OUTCOME MEASURES: Data on uncorrected (UCVA) and best-corrected visual acuity (BCVA), predictability, and stability of refraction and any complications were analyzed. RESULTS: Mean follow-up was 13.2 months. At the last postoperative examination, 26 eyes (92.8%) in the hyperopic group and 12 eyes (85.7%) in the myopic group had an UCVA superior to 20/40. Twelve hyperopic eyes (42.8%) and five myopic eyes (35.7%) had a UCVA of 20/20. All patients fell between 1 diopter of attempted correction in the spherical equivalent. Only 1 (2.4%) of the 42 eyes, belonging to the hyperopic group, lost 1 Snellen line of BCVA. We did not observe any decentration and/or haze after photorefractive keratectomy treatment or any irregularity in the flap-stroma interface in the three laser in situ keratomileusis operations performed in this study. CONCLUSIONS: The combination of topographic data with computer-controlled flying-spot excimer laser ablation is a suitable solution for correcting irregular astigmatism due to different causes.


Subject(s)
Astigmatism/surgery , Cornea/surgery , Corneal Topography , Hyperopia/surgery , Myopia/surgery , Photorefractive Keratectomy , Adult , Corneal Topography/instrumentation , Corneal Topography/methods , Female , Humans , Keratomileusis, Laser In Situ , Lasers, Excimer , Male , Middle Aged , Photorefractive Keratectomy/methods , Reproducibility of Results , Safety , Software , Treatment Outcome , Visual Acuity
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