[Show abstract][Hide abstract] ABSTRACT: Glaucoma occurs when there are imbalances
between the production and the drainage of the eye liquid.
The vast majority of the aqueous humor leaves the eye through
the trabecular meshwork (TM). The cause of hypertonicity
may be due to an alteration in the thickness of the TM. In
the majority of cases the molecular changes that determine
primary open‑angle glaucoma (POAG) are unclear. However,
it has been hypothesized that the significant increase in the
extracellular matrix (ECM) of the fibrillary bands in the
TM is associated with possible inflammatory conditions. In
this study the tissue distribution of interleukin (IL)‑6, IL‑1β,
transforming growth factor-β1 (TGF‑β1), vascular endo‑
thelial growth factor (VEGF) and tumor necrosis factor α
(TNF‑α) was analyzed in TM samples from patients with
POAG by immunohistochemistry. Seven specimens from
patients with POAG and three control tissues were analyzed
by immunohistochemistry using specific antibodies against
these cytokines. Morphological changes in the TM, such as
increased cell content, macrophages, fibrosis and accumula‑
tion of neutrophils, were observed by transmission electron
microscopy. In human TM tissues, an evident immunoreac‑
tivity for IL‑6, IL‑1β and TNF‑α was observed in patients with
POAG when compared with the control subjects, indicating
that these cytokines may be correlated with disease activity.
TM endothelial cells secrete a number of factors and cytokines
that modulate the functions of the cells and the ECM of the
conventional outflow pathway. In the TM in glaucoma, macro‑
phages produce cytokines, including IL‑6, IL‑1β and TNF‑α,
leading to an acute inflammatory response and recruitment
of other immune cells, including T lymphocytes. In addition,
TGF‑β1 regulates and induces the expression of IL‑6 in TM
that indirectly induces angiogenesis by stimulating VEGF
expression. The present results support previous evidence that
suggests that growth factors and cytokines can induce ECM
remodelling and alter cytoskeletal interactions in the TM.
Molecular Medicine Reports 05/2014; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune‑modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.
International Journal of Molecular Medicine 03/2014; · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Congenital diaphragmatic hernia is a major malformation occasionally found in newborns and babies. Congenital diaphragmatic hernia is defined by the presence of an orifice in the diaphragm, more often to the left and posterolateral, that permits the herniation of abdominal contents into the thorax. The aim of this case series is to provide information on the presentation, diagnosis and outcome of three patients with late-presenting congenital diaphragmatic hernias. The diagnosis of congenital diaphragmatic hernia is based on clinical investigation and is confirmed by plain X-ray films and computed tomography scans.Case presentations: In the present report three cases of asymptomatic abdominal viscera herniation within the thorax are described. The first case concerns herniation of some loops of the large intestine into the left hemi-thorax in a 75-year-old Caucasian Italian woman. The second case concerns a rare type of herniation in the right side of the thorax of the right kidney with a part of the liver parenchyma in a 57-year-old Caucasian Italian woman. The third case concerns herniation of the stomach and bowel into the left side of the chest with compression of the left lung in a 32-year-old Caucasian Italian man. This type of hernia may appear later in life, because of concomitant respiratory or gastrointestinal disease, or it may be an incidental finding in asymptomatic adults, such as in the three cases featured here. CONCLUSIONS: Patients who present with late diaphragmatic hernias complain of a wide variety of symptoms, and diagnosis may be difficult. Additional investigation and research appear necessary to better explain the development and progression of this type of disease.
Journal of Medical Case Reports 05/2013; 7(1):125.
[Show abstract][Hide abstract] ABSTRACT: The positive effects of spa therapy on ear, nose, and throat pathology are known but robust literature in this field, is still lacking. The aim of this study was to assess through a retrospective analysis, the effects on otitis media with effusion of Politzer endotympanic inhalation of sulphurous waters in children aged 5-9 years.
A cohort of 95 patients was treated with Politzer insufflations of sulphurous water: 58 patients did a cycle consisting of a treatment of 12 days per year for three consecutive years; 37 patients followed the same procedure for 5 years consecutively. The control population was represented by untreated, age-matched children. A standard audiometric test was used before and after each cycle of treatment.
One cycle of Politzer inhalation of sulphur-rich water improved the symptoms. Three cycles definitively stabilized the improvement of hearing function.
Our results show that otitis media with effusion in children can be resolved by an appropriate non-pharmacological treatment of middle ear with sulphur-rich water.
Clinical and Experimental Otorhinolaryngology 03/2013; 6(1):7-11. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.
International Journal of Molecular Medicine 10/2012; · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: This study presents our experience with a series of patients suffering from petrous bone fractures violating the otic capsule who underwent subtotal petrosectomy combined with eustachian tube, middle ear, and mastoid obliteration, with the goal of preventing cerebrospinal fluid (CSF) leak and meningitis. METHODS: This study enrolled 26 patients between 1997 and 2011. The clinical symptoms, otoscopy, and preoperative and postoperative audiometry and facial function, as well as CSF leak or meningitis, were evaluated in each patient. The entire group underwent a subtotal petrosectomy using the technique described in detail by Fisch. In addition, each patient was interviewed using a questionnaire to evaluate the impact on quality of life. RESULTS: Intraoperatively, we found significant CSF leaks in 14 patients (42.5%). No patient reported other episodes of CSF leak or meningitis after the surgery. The patients' responses of facial nerve function were slightly worse than the House-Brackmann evaluation (50% versus 42.3%; p < 0.05). The vast majority (88.5%) of the patients experienced no social impact. CONCLUSION: Our findings suggest the importance of not underestimating the risk for CSF leak in the petrous bone fractures violating the otic capsule.Preoperative counseling regarding the various troublesome complications must adequately motivate candidates to undergo surgery by pointing out the positive impact of the proposed treatment.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 09/2012; · 1.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The alkali-burned corneas of 12 rabbits were studied with fluorescence microscopy 1 week, 3 weeks, and 6 months after injury
to identify the arrangement of catecholaminergic nerve fibers (CNF) and related levels of norepinephrine. In the wounded corneas,
CNF were reduced at both 1 and 3 weeks and were restored by 6 months, as shown by histofluorescent staining. Biochemical results
showed that norepinephrine also passes through surviving, degenerating, and regenerating phases.
Annals of Ophthalmology 04/2012; 32(4):307-312. · 0.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.
International Journal of Molecular Medicine 01/2011; 27(4):561-5. · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Of the 234 orbital tumors treated surgically in the authors' Department between 1953 and 1989, ten were primary orbital lymphomas. The salient clinical, diagnostic and therapeutic data on these lesions, relatively uncommon in neurosurgical and ophthalmological practice, are analyzed and discussed in the light of the relevant published work.
[Show abstract][Hide abstract] ABSTRACT: The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.
[Show abstract][Hide abstract] ABSTRACT: Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of this innervation on the release of locally active molecules is still unclear. Lingual tonsils belong to Waldeyer's Ring, in close association with palatine tonsils and nasopharyngeal (adenoids) tonsils, thus constituting part of NALT (nasal-associated lymphoid tissue) together with the tubal tonsils and lateral pharyngeal bands. In this study, we focused our attention on the expression of some neurotrophins (NTs) and their high- and low-affinity receptors in human lingual tonsils. Light immunohistochemistry showed that human tonsillar samples were generally positive for all the NTs investigated (NGF, BDNF, NT-3, NT-4) and their receptors (TrKA, TrKB, TrKC and p75) with some different expression levels. NGF and TrKC were strongly expressed in macrophages, but weakly in lymphocytes. However, BDNF and TrKB was highly expressed in lymphocytes and weaker in macrophages. The low-affinity receptor for NGF, p75, was mainly moderately expressed in the analysed samples. These results suggest the presence of a pattern of neurotrophin innervation in the human lingual tonsil which may play a role in sustaining inflammatory conditions and in modulating a close interaction between the nervous system and the different immune cellular subtypes.
[Show abstract][Hide abstract] ABSTRACT: Compared to the normal epidermal epithelium, cholesteatomas have altered growth properties characterized by the excessive growth of keratinocytes leading to mucosal destruction. Either congenital or acquired, these lesions, which grow in the middle ear space, the petrous apex or the mastoid of temporal bones, are mostly considered benign skin tumoral lesions. However, many questions remain concerning their pathophysiology. Numerous studies have been proposed to identify those cholesteatoma lesions at risk of recurrence, a possible event that may cause hearing loss. We examined patients with petrous apex or mastoid cholesteatoma in order to analyze the expression of various neurotransmitters, neurotrophins and their receptors and the Ki-67 antigen for identification of a possible relationship between clinical outcome and histopathological behaviour in terms of the proliferative activity of cholesteatomas. Expression of the analyzed molecules was studied using immunohistochemical methods in seven adult patients with petrous apex cholesteatoma who underwent surgical removal of the lesion. Our results, in accordance with published data, confirm that Molecular Immunology Borstel-1 (MIB-1) and certain neurotransmitters could be useful in the prognostic evaluation of the risk of recurrence of aggressive forms of cholesteatoma.
Molecular Medicine Reports 05/2008; 1(3):347-53. · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Signal transduction from plasma membrane to cell nucleus is a complex process depending on various components including lipid signaling molecules, in particular phosphoinositides and their related enzymes, which act at cell periphery and/or plasma membrane as well as at nuclear level. As far as the nervous system may concern the inositol lipid cycle has been hypothesized to be involved in numerous neural as well as glial functions. In this context, however, a precise panel of glial PLC isoforms has not been determined yet. In the present experiments we investigated astrocytic PLC isoforms in astrocytes obtained from foetal primary cultures of rat brain and from an established cultured (C6) rat astrocytoma cell line, two well known cell models for experimental studies on glia. Identification of PLC isoforms was achieved by using a combination of RT-PCR and immunocytochemistry experiments. While in both cell models the most represented PI-PLC isoforms were beta4, gamma1, delta4, and epsilon, isoforms PI-PLC beta2 and delta3 were not detected. Moreover, in primary astrocyte cultures PI-PLC delta3 resulted well expressed in C6 cells but was absent in astrocytes. Immunocytochemistry performed with antibodies against specific PLC isoforms substantially confirmed this pattern of expression both in astrocytes and C6 glioma cells. In particular while some isoenzymes (namely isoforms beta3 and beta4) resulted mainly nuclear, others (isoforms delta4 and epsilon) were preferentially localized at cytoplasmic and plasma membrane level.
Journal of Cellular Biochemistry 04/2007; 100(4):952-9. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of these neuromediators on the release of locally active molecules is still unknown. Here we focused our attention on the expression of some neurotrophins (NTs), their high- and low-affinity receptors and several neurotransmitters in human palatine tonsils. Light and electron microscopy immunohistochemistry showed that human tonsillar samples were positive for all analyzed neurotrophins (NGF, BDNF and NT-3) and their high-affinity receptors (TrkA, TrkB and TrkC, respectively). All of these molecules were strongly expressed in macrophages whereas, in some patients, a weaker specific staining of lymphocytes and blood vessels was also found. The low-affinity receptor for NGF (p75) was always absent in the analysed samples. RT-PCR confirmed the occurrence of specific transcripts for NTs and their high-affinity receptors as well as the absence of mRNA for p75 protein. Also, specific immunoreactivity for neurotransmitters SP, VIP, CGRP, ChAT and nNOS was mainly expressed by macrophagic cells. These results suggest the presence of an extensive network of innervation in the human palatine tonsils which may play a role in the regulation of some immune functions as well as in the modulation of a possible functional scenario of interactions among different immune cellular subtypes.
International Journal of Molecular Medicine 08/2006; 18(1):49-58. · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial dysfunctions have been implicated in the pathophysiology of several age-related diseases including age-related macular degeneration (AMD), a progressive neurodegenerative disease affecting primarily the retinal pigment epithelium (RPE). The aims of our electron microscopic and morphometric studies were to reveal qualitative and quantitative alterations of mitochondria in human RPE from AMD and from age- and sex-matched controls. With increasing age a significant decrease in number and area of mitochondria, as well as loss of cristae and matrix density were found in both AMD and control specimens. These decreases were significantly greater in AMD than in normal aging. Alterations of mitochondria were accompanied by proliferation of peroxisomes and lipofuscin granules in both AMD and control specimens, although the difference between groups was significant only for peroxisomes. Unexpectedly, morphometric data showed that the RPE alterations seen in AMD may also develop in normal aging, 10-15 years after appearing in AMD patients. These findings suggest that (i) the severity of mitochondrial and peroxisomal alterations are different between AMD and normal aging, and (ii) the timing of damage to RPE may be critical for the development of AMD. We conclude that besides the well-documented age-related changes in mitochondrial DNA, alterations of mitochondrial membranes may also play a role in the pathogenesis of AMD. These membranes could be a new target for treatment of AMD and other age-related diseases.
Neurobiology of Aging 08/2006; 27(7):983-93. · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant transformation of breast epithelia is frequently associated with an altered expression of MHC products and of antigen processing molecular machinery. The consequent impairment of tumor immune recognition is thought to confer to tumor cells a selective advantage with respect to survival and metastatization. In order to understand if metastatic breast cancer lesions might be associated with a defective proteasome subunit expression that, in turn, might limit the peptide availability and prevent stable cell surface HLA class I-tumor antigen expression, we studied by immunostaining the expression of beta2-microglobulin, HLA class I antigens and proteasome subunits LMP-2 and LMP-10 in 35 matched primary and metastatic human breast carcinoma lesions. Overall, we found a downregulation of LMP-2 in 51.4% of the lesions, of LPM-10 in 45.7% of the lesions, of HLA class I heavy chain in 40.0% of the lesions, while beta2-microglobulin was downregulated in 25.7% of the lesions studied. In most primary and metastatic lesions the downmodulation of each antigen examined was coordinated. In the cases where a selective downmodulation of antigens was observed in the primary or in the metastatic lesion (with the exception of beta2-microglobulin), it was rather observed in the primary lesions. However, LMP-10 showed a significant selective downmodulation in the metastases as well. Antigen downmodulation does not appear therefore to represent a strategy for the primary tumor to metastasize successfully.
International Journal of Oncology 01/2005; 25(6):1625-9. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.
International Journal of Molecular Medicine 11/2004; 14(4):615-20. · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a previous study, scanning electron microscopy (SEM) showed age-related changes in the rat retina. We carried out a study to evaluate age-related changes in the human retina.
Samples of fresh retinal tissue obtained from younger (age 22 years or less) and older (age 66 years or more) donors were studied by means of traditional histologic methods and by SEM. Eight retinas were obtained from four donors whose corneas had been used for transplantation, and four retinas were obtained from four subjects whose eyes had been enucleated owing to injury. All morphologic results were subjected to quantitative analysis of images. The concentration of cytoplasmic (free) and structural (tissue-associated) protein in retinal tissue homogenates was determined by means of biochemical methods.
There was a decrease in all features studied with the exception of structural protein concentration. The mean retinal thickness (and standard error of the mean) was 426 (34.2) microm in the younger subjects and 261 (18.9) microm in the older subjects. The mean numbers of ganglion cells (and standard error of the mean) were 413.5/mm2 (32.3/mm2) and 256.2/mm2 (26.8/mm2) respectively, of capillaries 3.6/mm2 (1.4/mm2) and 1.8/mm2 (1.2/mm2) respectively, of synaptic bodies 122.4 (4.9) conventional units (CU)/area observed and 38.5 (1.6) CU/area observed respectively, of cellular processes 82.3 (3.1) CU/area observed and 13.1 (1.5) CU/ area observed respectively, and of intercellular connections 36.4 (2.5) CU/area observed and 14.3 (1.4) CU/area observed respectively. The mean concentration of total protein per milligram of fresh tissue (and standard error of the mean) was 92.1 (1.8) microg in the younger subjects and 78.7 (1.3) microg in the older subjects; the corresponding values for cytoplasmic protein were 27.6 (1.3) microg and 11.8 (0.8) microg, and for structural protein, 64.4 (1.6) microg and 86.9 (1.4) microg. All differences between the younger and older subjects were significant (p < 0.001) with the exception of mean concentration of cytoplasmic and of structural protein.
The human retina undergoes specific changes with aging. SEM provides new morphometric information regarding age-related changes in photoreceptor cells, bipolar cells and ganglion cells that increases our understanding of this topic. Our results may be adopted as a model or as normal values when studying other changes that may occur in the human retina in pathological conditions.
Canadian Journal of Ophthalmology 03/2004; 39(1):61-8. · 1.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the use of autologous bone for reconstruction of the cranial and facial skeleton underwent a partial reappraisal following the introduction of a vast range of alloplastic materials for this purpose, it has demonstrated definite advantages over the last century and, particularly, during the last decade.
Fifteen patients underwent cranial and/or cranio-facial reconstruction using autologous bone grafting in the Department of Neurologic Sciences-Neurosurgery and the Division of Maxillo-Facial Surgery of the Rome "La Sapienza" University between 1987 and 1995. This group of patients consisted of 8 females and 7 males whose average age was 29.5 years (range 7.5 to 59 years, mean age 30). In all these patients cranioplasty and/or cranio-facial reconstruction had been performed to repair bone defects secondary to benign tumors or tumor-like lesions (12 cases), trauma (2 cases), or, in the remaining case, to wound infection after craniotomy for a neurosurgical operation.
The results obtained in a series of 15 patients treated using this method are described with reference to the abundant data published on this topic.
The mechanical, immunologic, and technical-grafting properties of autologous bone, together with its superior esthetic and psychological effects, probably make it the best material for cranioplasty.
[Show abstract][Hide abstract] ABSTRACT: The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.