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Papers by Nila Volpi

Research paper thumbnail of Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy

European Journal of Ophthalmology

Introduction Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathog... more Introduction Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. Case report A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal micr...

Research paper thumbnail of Study of total duration of distal compound muscle action potential in demyelinating and axonal Guillain-Barre’ syndrome

Research paper thumbnail of Elongated styloid process: literature review and morphometric data on a collection of dried skulls

Italian Journal of Anatomy and Embryology

The styloid process is a subtle process of variable length that originates from the petrous part ... more The styloid process is a subtle process of variable length that originates from the petrous part of temporal bone . From the process originate three muscles: the stylopharyngeus,the styloglossus, the stylohyoideus and two ligaments :stylohyoid and stylomandibular . The styled process of the temporal bone has a variable length as demonstrated for studies conducted in three-dimensional computed tomography or dental panoramic three-dimensional scanning,and in dried skulls The normal length of the styloid process is particularly important to establish for the relations of closeness with vascular and nervous structures and their possible compression by an elongated styloid process.Several studies have focused on the effects of changes in length and course of the styloid process, highlighting the relations of the carotid artery and the glossopharyngeal nerve to explain cerebrovascular symptoms or Eagle’s syndrome characterized by neck pain and dysphagia .However the association for the ab...

Research paper thumbnail of Additional file 1: of Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Viability and apoptosis (left panel) and qPCR and ICC (right panel) data regarding control fibrob... more Viability and apoptosis (left panel) and qPCR and ICC (right panel) data regarding control fibroblasts stimulated with specific SSc-autoantibodies (anti-Cenp-B, anti-Topo-I IgGs 1:100) and with SSc-unrelated one (anti-Histone H3 IgGs 1:100) with and without the pre-incubation (2 h) with an anti-apoptotic compound (IAP, AZD 5582 dihydrochloride, 50 nM) (*p

Research paper thumbnail of Osteologic topography of the trochlear spine and fovea as landmarks to locate the superior oblique trochlea

The position of the superior oblique tendon, attached to the orbital roof by a cartilaginous troc... more The position of the superior oblique tendon, attached to the orbital roof by a cartilaginous trochlea, is marked by osteologic landmarks like the trochlear spine and/or fovea, approximately located at the superomedial angle of the orbit. Aim of the study is to place the trochlea within the orbit with a series of measurements to give the surgeon detailed references of the trochlea location. For this purpose, we undertook the study of a collection of dry skulls of known sex and age to investigate bony landmarks. Measurements were taken to assess the position of the trochlear spine/fovea on a frontal plane employing a system of vertical and horizontal lines passing through known bony reference points. Measurements were also recorded between the trochlear spine/fovea and the orbital opening on one side and the anterior rim of the optic canal on the other side. The distances of the trochlear spine/fovea from the lines passing along the supraorbital notch and the frontozygomatic suture were respectively 8.5 ± 2.3 mm and 5.7 ± 1.5 mm. The distances of the trochlear fovea/spine from the anterior orbital opening and from the anterior rim of the optic foramen were respectively 4.2 ± 0.11 and 37.5 ± 3.1 mm. Only the distance from the optic canal showed sex-related differences. In conclusion, to avoid unwanted injuries of the trochlea of the superior oblique in surgery of the superomedial angle of the orbit, the surgeon should be aware of its precise position.

Research paper thumbnail of Headache, seizures and repeated strokes in a young subject: A new case of MELAS-like syndrome?

Research paper thumbnail of Correlazioni cliniche, biochimiche e molecolari in 15 casi di Oftalmoplegia cronica progressiva

Correlazioni cliniche, biochimiche e molecolari in 15 casi di Oftalmoplegia cronica progressiv

Research paper thumbnail of Scleredema adultorum con coinvolgimento muscolare in paziente diabetica

Research paper thumbnail of Heat shock protein 70 in human ocular muscles: immunocytochemical, and immunochemical study

Research paper thumbnail of Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Arthritis Research & Therapy, 2019

Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become re... more Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc. The aim of the study is to assess the pathogenic capacity of anti-DNA-topoisomerase I (anti-Topo-I) and anti-centromeric protein B (anti-Cenp-B) autoantibodies to induce pro-fibrotic markers in dermal fibroblasts. Methods: Dermal fibroblasts were isolated from unaffected and affected skin samples of (n = 10) limited cutaneous SSc (LcSSc) patients, from affected skin samples of diffuse cutaneous (DcSSc) patients (n = 10) and from healthy subjects (n = 20). Fibroblasts were stimulated with anti-Topo-I, anti-Cenp-B IgGs, and control IgGs in ratios 1:100 and 1:200 for 24 h. Cells were also incubated with 10% SSc anti-Topo-I + and anti-Cenp-B + whole serum and with 10% control serum for 24 h. Viability was assessed by MTT test, while apoptosis was assessed by flow cytometry. Activation of pro-fibrotic genes ACTA2, COL1A1, and TAGLN was evaluated by quantitative real-time PCR (qPCR), while the respective protein levels alpha-smooth-muscle actin (α-SMA), type-I-collagen (Col-I), and transgelin (SM22) were assessed by immunocytochemistry (ICC). Results: MTT showed that anti-Cenp-B/anti-Topo-I IgGs and anti-Cenp-B + /anti-Topo-I + sera reduced viability (in a dilutiondependent manner for IgGs) for all the fibroblast populations. Apoptosis is induced in unaffected LcSSc and control fibroblasts, while affected LcSSc/DcSSc fibroblasts showed apoptosis resistance. Basal mRNA (ACTA2, COL1A1, and TAGLN) and protein (α-SMA, Col-1, and SM22) levels were higher in affected LcSSc/DcSSc fibroblasts compared to LcSSc unaffected and to control ones. Stimulation with anti-Cenp-B/anti-Topo-I IgGs and with anti-Cenp-B + /anti-Topo-I + sera showed a better induction in unaffected LcSSc and control fibroblasts. However, a statistically significant increase of all pro-fibrotic markers is reported also in affected LcSSc/DcSSc fibroblasts upon stimulation with both IgGs and sera. Conclusions: This study suggests a pathogenic role of SSc-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. Therefore, besides the diagnostic and prognostic use of those autoantibodies, these data might further justify the importance of immunosuppressive drugs in the early stages of the autoimmune disease, including SSc.

Research paper thumbnail of A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures

International Journal of Molecular Sciences, 2018

Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthriti... more Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were...

Research paper thumbnail of Trehalose inhibits cell proliferation and amplifies long‐term temozolomide‐ and radiation‐induced cytotoxicity in melanoma cells: A role for autophagy and premature senescence

Journal of Cellular Physiology, 2018

Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherap... more Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherapy (RT) offering little control of these lesions. We tested whether trehalose, a natural glucose disaccharide proved to induce autophagy, could enhance the effect of TMZ and ionizing radiation (IR). In two melanoma cell lines (A375 and SK-Mel-28), which greatly differ in chemosensitivity and radiosensitivity, trehalose significantly inhibited short-term cell proliferation and also enhanced IR-induced cytostasis. Interestingly, in TMZ-resistant SK-Mel-28 cells, trehalose was more effective than TMZ, and combined trehalose + TMZ further reduced cell proliferation. In long-term experiments, colony-forming capacity was dramatically reduced by trehalose, and even more by combined trehalose + TMZ or trehalose + IR. In resistant SK-Mel-28 cells, although growth was inhibited most with trehalose + TMZ + IR-6 Gy combined treatment, it is notable that trehalose + TMZ treatment was also very effective. Along with a direct antiproliferative effect, two further mechanisms may explain how trehalose potentiates TMZ-and IR-induced effects: the remarkable trehalose-stimulated autophagy in A375 cells, which were sensitive to TMZ-and IR-induced apoptosis; and the notable trehalose-stimulated premature senescence in SK-Mel-28 cells, which were resistant to apoptosis and less prone to autophagy. In normal melanocytes, trehalose induced a minor autophagy and cell proliferation inhibition, without affecting cell viability; moreover, when trehalose was used in combination with TMZ, the slight TMZinduced cytotoxicity was not significantly reinforced. Together, our results suggest that trehalose, a safe nutrient supplement able to cross the blood-brain barrier, is a promising candidate, worthy to be further explored in vivo, to augment the therapeutic efficacy of TMZ and RT in melanoma brain metastases.

Research paper thumbnail of Methylsulfonylmethane and mobilee prevent negative effect of IL-1β in human chondrocyte cultures via NF-κB signaling pathway

International Immunopharmacology, 2018

Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable sa... more Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable safety profile. Recent studies showed their potential activity on osteoarthritis (OA) inflammation and cartilage metabolism. We investigated the effect of methylsulfonylmethane (MSM) and mobilee in human OA chondrocyte cultures exposed to interleukin (IL)-1β. OA cartilage was obtained from femoral heads of five patients undergoing total replacement surgery. Chondrocytes were incubated with mobilee (200 and 500 μM) and MSM (2000 and 6000 μM) in presence of IL-1β (10 ng/mL) and nuclear factor (NF)-κB inhibitor (BAY 11-7082, 1 μM), for 24 and 48 h. Viability and apoptosis were performed by MMT and flow cytometry. The metalloproteinase (MMP)-1,-3,-13 and type II collagen (Col2a1) were analyzed by qRT-PCR and ELISA, and NF-κB activation by immunofluorescence. IL-1β stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline. Mobilee and MSM incubation significantly reversed the effect of IL-1β. IL-1β significantly induced NF-κB p50 nuclear translocation, which was significantly counteracted by the pre-treatment of OA chodrocytes with the tested compounds. BAY11-7082 significantly modulated MMPs and Col2a1 expression respectively to basal state. Co-treatment of IL-1β with mobilee, MSM and BAY11-7082 didn't cause changes of MMPs or Col2a1 beyond that caused by each single treatment. We demonstrated that MSM and mobilee have a beneficial effect on OA chondrocytes metabolism, probably due to the modulation of NF-κB pathway, providing a powerful rationale for the use of these substances in OA treatment.

Research paper thumbnail of Sensory-motor axonal multineuropathy during etanercept therapy for rheumatoid arthritis

Clinical and experimental rheumatology

Research paper thumbnail of Localization of RXFP1/LGR7 Receptor in Scleroderma

Research paper thumbnail of Peptidergic innervation of mesenteric lymphatics in guinea pigs: an immunocytochemical and pharmacological study

Lymphology, 1991

By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immu... more By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibers were examined in guinea pig mesenteric lymph collectors. The immunoreactive nerve fibers, located in the adventitia of lymphatics, were few and were irregularly distributed along the vessel wall. These fibers appeared to be more numerous and more evenly distributed along the corresponding artery and vein walls within the same area. SP immunoreactivity in the vascular nerves was depleted in guinea pigs injected with capsaicin but was unaffected by the injection of 6-hydroxydopamine. By contrast, VIP-IR nerve fibers were unaffected by both treatments. It is concluded that SP-IR nerve fibers in the lymphatics are likely to be of sensory origin and that VIP containing nerves in the lymph collectors are distinct from SP-containing and noradrenergic nerves. It is also suggested that lymph collectors possess a complex although limited innervation pattern not onl...

Research paper thumbnail of F2-Isoprostanes in soft oral tissues and degree of oral disability after mandibular third molar surgery

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2012

The aim of this study was to test the value of F 2-isoprostane (F 2-IsoP) levels in the pericoron... more The aim of this study was to test the value of F 2-isoprostane (F 2-IsoP) levels in the pericoronal gingiva as a potential predictor of oral disability after mandibular third molar (M3M) surgery. Study design. Thirteen patients (5 male, 8 female) with partially impacted M3M were enrolled. Pericoronal soft tissues histology was obtained, gingival F 2-IsoPs were measured by gas chromatography/negative-ion chemical ionization tandem mass spectrometry, and health-related quality of life (HRQOL) scores were assessed. Results. A variable degree of pericoronitis was evident before the M3M surgery, with a mean level of pericoronal F 2-IsoPs of 634.8 Ϯ 193.5 pg/mg of tissue. A significant positive correlation between pericoronal F 2-IsoPs and HRQOL was observed in male (r s ϭ 0.440; P ϭ .0011), but not female (r s ϭ Ϫ0.062; P ϭ .5124) patients. Conclusions. Levels of F 2-IsoPs in the pericoronal soft tissues are correlated with the degree of oral disability after M3Ms surgery in male, but not female, patients.

Research paper thumbnail of Human osteoarthritic chondrocytes exposed to extremely low-frequency electromagnetic fields (ELF) and therapeutic application of musically modulated electromagnetic fields (TAMMEF) systems: a comparative study

Rheumatology International, 2012

Osteoarthritis (OA) is the most common joint disease, characterized by matrix degradation and cha... more Osteoarthritis (OA) is the most common joint disease, characterized by matrix degradation and changes in chondrocyte morphology and metabolism. Literature reported that electromagnetic fields (EMFs) can produce benefits in OA patients, even if EMFs mechanism of action is debated. Human osteoarthritic chondrocytes isolated from femoral heads were cultured in vitro in bidimensional (2-D) flasks and in three-dimensional (3-D) alginate beads to mimic closely cartilage environment in vivo. Cells were exposed 30 min/day for 2 weeks to extremely low-frequency electromagnetic field (ELF) with fixed frequency (100 Hz) and to therapeutic application of musically modulated electromagnetic field (TAMMEF) with variable frequencies, intensities, and waveforms. Cell viability was measured at days 7 and 14, while healthy-cell density, heavily vacuolized (hv) cell density, and cluster density were measured by light microscopy only for 3-D cultures after treatments. Cell morphology was observed for 2-D and 3-D cultures by transmission electron microscopy (TEM). Chondrocyte exposure to TAMMEF enhances cell viability at days 7 and 14 compared to ELF. Light microscopy analysis showed that TAMMEF enhances healthy-cell density, reduces hv-cell density and clustering, compared to ELF. Furthermore, TEM analysis showed different morphology for 2-D (fibroblast-like) and 3-D (rounded shape) cultures, confirming light microscopy results. In conclusion, EMFs are effective and safe for OA chondrocytes. TAMMEF can positively interfere with OA chondrocytes representing an innovative non-pharmacological approach to treat OA.

Research paper thumbnail of Paraneoplastic necrotizing myopathy associated with adenocarcinoma of the lung – a rare entity with atypical onset: a case report

Journal of Medical Case Reports, 2013

Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recogni... more Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recognized paraneoplastic syndromes. However, paraneoplastic necrotizing myopathy is a more recently defined clinical entity, characterized by rapidly progressive, symmetrical, predominantly proximal muscle weakness with severe disability, and associated with a marked increase in serum muscle enzyme levels. Paraneoplastic necrotizing myopathy requires muscle biopsy for diagnosis, which typically shows massive necrosis of muscle fibers with limited or absent inflammatory infiltrates. Case presentation: We report the case of an 82-year-old Italian-born Caucasian man who was admitted to hospital because of heart failure and two drop attacks. Over the following days, he developed progressive severe weakness, dysphagia, and dysphonia. Testing showed increasing serum muscle enzyme levels. Electromyography showed irritative myopathy of the proximal muscles and sensorimotor polyneuropathy. Muscle biopsy (left vastus lateralis) showed massive necrosis of muscle fibers with negligible inflammatory infiltrates, complement membrane attack complex deposition on endomysial capillaries, and moderate upregulation of major histocompatibility complex-I. Computed tomography of the thorax showed a nodular mass in the apex of the right lung. The patient was diagnosed with paraneoplastic necrotizing myopathy. In spite of high-dose corticoid therapy, he died 1 month later because of his aggressive cancer. Subsequent electron microscopic examination of a muscle biopsy specimen showed thickened walls and typical pipestem changes of the endomysial capillaries, with swollen endothelial cells. Poorly differentiated adenocarcinoma of the lung was confirmed on post-mortem histological examination. Conclusions: Paraneoplastic necrotizing myopathy is a rare syndrome with outcomes ranging from fast progression to complete recovery. Treatment with corticosteroids is often ineffective, and prognosis depends mainly on the characteristics of the underlying cancer. This case shows that paraneoplastic necrotizing myopathy may have an atypical appearance, and should be considered in elderly patients with neoplastic disease. In this case, the diagnosis was delayed by the unusual clinical picture that suggested heart disease rather than muscle disease.

Research paper thumbnail of Human placenta and fetal membranes express nerve growth factor mRNA and protein

Journal of Endocrinological Investigation, 2006

Research paper thumbnail of Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy

European Journal of Ophthalmology

Introduction Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathog... more Introduction Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. Case report A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal micr...

Research paper thumbnail of Study of total duration of distal compound muscle action potential in demyelinating and axonal Guillain-Barre’ syndrome

Research paper thumbnail of Elongated styloid process: literature review and morphometric data on a collection of dried skulls

Italian Journal of Anatomy and Embryology

The styloid process is a subtle process of variable length that originates from the petrous part ... more The styloid process is a subtle process of variable length that originates from the petrous part of temporal bone . From the process originate three muscles: the stylopharyngeus,the styloglossus, the stylohyoideus and two ligaments :stylohyoid and stylomandibular . The styled process of the temporal bone has a variable length as demonstrated for studies conducted in three-dimensional computed tomography or dental panoramic three-dimensional scanning,and in dried skulls The normal length of the styloid process is particularly important to establish for the relations of closeness with vascular and nervous structures and their possible compression by an elongated styloid process.Several studies have focused on the effects of changes in length and course of the styloid process, highlighting the relations of the carotid artery and the glossopharyngeal nerve to explain cerebrovascular symptoms or Eagle’s syndrome characterized by neck pain and dysphagia .However the association for the ab...

Research paper thumbnail of Additional file 1: of Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Viability and apoptosis (left panel) and qPCR and ICC (right panel) data regarding control fibrob... more Viability and apoptosis (left panel) and qPCR and ICC (right panel) data regarding control fibroblasts stimulated with specific SSc-autoantibodies (anti-Cenp-B, anti-Topo-I IgGs 1:100) and with SSc-unrelated one (anti-Histone H3 IgGs 1:100) with and without the pre-incubation (2 h) with an anti-apoptotic compound (IAP, AZD 5582 dihydrochloride, 50 nM) (*p

Research paper thumbnail of Osteologic topography of the trochlear spine and fovea as landmarks to locate the superior oblique trochlea

The position of the superior oblique tendon, attached to the orbital roof by a cartilaginous troc... more The position of the superior oblique tendon, attached to the orbital roof by a cartilaginous trochlea, is marked by osteologic landmarks like the trochlear spine and/or fovea, approximately located at the superomedial angle of the orbit. Aim of the study is to place the trochlea within the orbit with a series of measurements to give the surgeon detailed references of the trochlea location. For this purpose, we undertook the study of a collection of dry skulls of known sex and age to investigate bony landmarks. Measurements were taken to assess the position of the trochlear spine/fovea on a frontal plane employing a system of vertical and horizontal lines passing through known bony reference points. Measurements were also recorded between the trochlear spine/fovea and the orbital opening on one side and the anterior rim of the optic canal on the other side. The distances of the trochlear spine/fovea from the lines passing along the supraorbital notch and the frontozygomatic suture were respectively 8.5 ± 2.3 mm and 5.7 ± 1.5 mm. The distances of the trochlear fovea/spine from the anterior orbital opening and from the anterior rim of the optic foramen were respectively 4.2 ± 0.11 and 37.5 ± 3.1 mm. Only the distance from the optic canal showed sex-related differences. In conclusion, to avoid unwanted injuries of the trochlea of the superior oblique in surgery of the superomedial angle of the orbit, the surgeon should be aware of its precise position.

Research paper thumbnail of Headache, seizures and repeated strokes in a young subject: A new case of MELAS-like syndrome?

Research paper thumbnail of Correlazioni cliniche, biochimiche e molecolari in 15 casi di Oftalmoplegia cronica progressiva

Correlazioni cliniche, biochimiche e molecolari in 15 casi di Oftalmoplegia cronica progressiv

Research paper thumbnail of Scleredema adultorum con coinvolgimento muscolare in paziente diabetica

Research paper thumbnail of Heat shock protein 70 in human ocular muscles: immunocytochemical, and immunochemical study

Research paper thumbnail of Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Arthritis Research & Therapy, 2019

Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become re... more Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc. The aim of the study is to assess the pathogenic capacity of anti-DNA-topoisomerase I (anti-Topo-I) and anti-centromeric protein B (anti-Cenp-B) autoantibodies to induce pro-fibrotic markers in dermal fibroblasts. Methods: Dermal fibroblasts were isolated from unaffected and affected skin samples of (n = 10) limited cutaneous SSc (LcSSc) patients, from affected skin samples of diffuse cutaneous (DcSSc) patients (n = 10) and from healthy subjects (n = 20). Fibroblasts were stimulated with anti-Topo-I, anti-Cenp-B IgGs, and control IgGs in ratios 1:100 and 1:200 for 24 h. Cells were also incubated with 10% SSc anti-Topo-I + and anti-Cenp-B + whole serum and with 10% control serum for 24 h. Viability was assessed by MTT test, while apoptosis was assessed by flow cytometry. Activation of pro-fibrotic genes ACTA2, COL1A1, and TAGLN was evaluated by quantitative real-time PCR (qPCR), while the respective protein levels alpha-smooth-muscle actin (α-SMA), type-I-collagen (Col-I), and transgelin (SM22) were assessed by immunocytochemistry (ICC). Results: MTT showed that anti-Cenp-B/anti-Topo-I IgGs and anti-Cenp-B + /anti-Topo-I + sera reduced viability (in a dilutiondependent manner for IgGs) for all the fibroblast populations. Apoptosis is induced in unaffected LcSSc and control fibroblasts, while affected LcSSc/DcSSc fibroblasts showed apoptosis resistance. Basal mRNA (ACTA2, COL1A1, and TAGLN) and protein (α-SMA, Col-1, and SM22) levels were higher in affected LcSSc/DcSSc fibroblasts compared to LcSSc unaffected and to control ones. Stimulation with anti-Cenp-B/anti-Topo-I IgGs and with anti-Cenp-B + /anti-Topo-I + sera showed a better induction in unaffected LcSSc and control fibroblasts. However, a statistically significant increase of all pro-fibrotic markers is reported also in affected LcSSc/DcSSc fibroblasts upon stimulation with both IgGs and sera. Conclusions: This study suggests a pathogenic role of SSc-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. Therefore, besides the diagnostic and prognostic use of those autoantibodies, these data might further justify the importance of immunosuppressive drugs in the early stages of the autoimmune disease, including SSc.

Research paper thumbnail of A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures

International Journal of Molecular Sciences, 2018

Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthriti... more Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were...

Research paper thumbnail of Trehalose inhibits cell proliferation and amplifies long‐term temozolomide‐ and radiation‐induced cytotoxicity in melanoma cells: A role for autophagy and premature senescence

Journal of Cellular Physiology, 2018

Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherap... more Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherapy (RT) offering little control of these lesions. We tested whether trehalose, a natural glucose disaccharide proved to induce autophagy, could enhance the effect of TMZ and ionizing radiation (IR). In two melanoma cell lines (A375 and SK-Mel-28), which greatly differ in chemosensitivity and radiosensitivity, trehalose significantly inhibited short-term cell proliferation and also enhanced IR-induced cytostasis. Interestingly, in TMZ-resistant SK-Mel-28 cells, trehalose was more effective than TMZ, and combined trehalose + TMZ further reduced cell proliferation. In long-term experiments, colony-forming capacity was dramatically reduced by trehalose, and even more by combined trehalose + TMZ or trehalose + IR. In resistant SK-Mel-28 cells, although growth was inhibited most with trehalose + TMZ + IR-6 Gy combined treatment, it is notable that trehalose + TMZ treatment was also very effective. Along with a direct antiproliferative effect, two further mechanisms may explain how trehalose potentiates TMZ-and IR-induced effects: the remarkable trehalose-stimulated autophagy in A375 cells, which were sensitive to TMZ-and IR-induced apoptosis; and the notable trehalose-stimulated premature senescence in SK-Mel-28 cells, which were resistant to apoptosis and less prone to autophagy. In normal melanocytes, trehalose induced a minor autophagy and cell proliferation inhibition, without affecting cell viability; moreover, when trehalose was used in combination with TMZ, the slight TMZinduced cytotoxicity was not significantly reinforced. Together, our results suggest that trehalose, a safe nutrient supplement able to cross the blood-brain barrier, is a promising candidate, worthy to be further explored in vivo, to augment the therapeutic efficacy of TMZ and RT in melanoma brain metastases.

Research paper thumbnail of Methylsulfonylmethane and mobilee prevent negative effect of IL-1β in human chondrocyte cultures via NF-κB signaling pathway

International Immunopharmacology, 2018

Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable sa... more Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable safety profile. Recent studies showed their potential activity on osteoarthritis (OA) inflammation and cartilage metabolism. We investigated the effect of methylsulfonylmethane (MSM) and mobilee in human OA chondrocyte cultures exposed to interleukin (IL)-1β. OA cartilage was obtained from femoral heads of five patients undergoing total replacement surgery. Chondrocytes were incubated with mobilee (200 and 500 μM) and MSM (2000 and 6000 μM) in presence of IL-1β (10 ng/mL) and nuclear factor (NF)-κB inhibitor (BAY 11-7082, 1 μM), for 24 and 48 h. Viability and apoptosis were performed by MMT and flow cytometry. The metalloproteinase (MMP)-1,-3,-13 and type II collagen (Col2a1) were analyzed by qRT-PCR and ELISA, and NF-κB activation by immunofluorescence. IL-1β stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline. Mobilee and MSM incubation significantly reversed the effect of IL-1β. IL-1β significantly induced NF-κB p50 nuclear translocation, which was significantly counteracted by the pre-treatment of OA chodrocytes with the tested compounds. BAY11-7082 significantly modulated MMPs and Col2a1 expression respectively to basal state. Co-treatment of IL-1β with mobilee, MSM and BAY11-7082 didn't cause changes of MMPs or Col2a1 beyond that caused by each single treatment. We demonstrated that MSM and mobilee have a beneficial effect on OA chondrocytes metabolism, probably due to the modulation of NF-κB pathway, providing a powerful rationale for the use of these substances in OA treatment.

Research paper thumbnail of Sensory-motor axonal multineuropathy during etanercept therapy for rheumatoid arthritis

Clinical and experimental rheumatology

Research paper thumbnail of Localization of RXFP1/LGR7 Receptor in Scleroderma

Research paper thumbnail of Peptidergic innervation of mesenteric lymphatics in guinea pigs: an immunocytochemical and pharmacological study

Lymphology, 1991

By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immu... more By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibers were examined in guinea pig mesenteric lymph collectors. The immunoreactive nerve fibers, located in the adventitia of lymphatics, were few and were irregularly distributed along the vessel wall. These fibers appeared to be more numerous and more evenly distributed along the corresponding artery and vein walls within the same area. SP immunoreactivity in the vascular nerves was depleted in guinea pigs injected with capsaicin but was unaffected by the injection of 6-hydroxydopamine. By contrast, VIP-IR nerve fibers were unaffected by both treatments. It is concluded that SP-IR nerve fibers in the lymphatics are likely to be of sensory origin and that VIP containing nerves in the lymph collectors are distinct from SP-containing and noradrenergic nerves. It is also suggested that lymph collectors possess a complex although limited innervation pattern not onl...

Research paper thumbnail of F2-Isoprostanes in soft oral tissues and degree of oral disability after mandibular third molar surgery

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2012

The aim of this study was to test the value of F 2-isoprostane (F 2-IsoP) levels in the pericoron... more The aim of this study was to test the value of F 2-isoprostane (F 2-IsoP) levels in the pericoronal gingiva as a potential predictor of oral disability after mandibular third molar (M3M) surgery. Study design. Thirteen patients (5 male, 8 female) with partially impacted M3M were enrolled. Pericoronal soft tissues histology was obtained, gingival F 2-IsoPs were measured by gas chromatography/negative-ion chemical ionization tandem mass spectrometry, and health-related quality of life (HRQOL) scores were assessed. Results. A variable degree of pericoronitis was evident before the M3M surgery, with a mean level of pericoronal F 2-IsoPs of 634.8 Ϯ 193.5 pg/mg of tissue. A significant positive correlation between pericoronal F 2-IsoPs and HRQOL was observed in male (r s ϭ 0.440; P ϭ .0011), but not female (r s ϭ Ϫ0.062; P ϭ .5124) patients. Conclusions. Levels of F 2-IsoPs in the pericoronal soft tissues are correlated with the degree of oral disability after M3Ms surgery in male, but not female, patients.

Research paper thumbnail of Human osteoarthritic chondrocytes exposed to extremely low-frequency electromagnetic fields (ELF) and therapeutic application of musically modulated electromagnetic fields (TAMMEF) systems: a comparative study

Rheumatology International, 2012

Osteoarthritis (OA) is the most common joint disease, characterized by matrix degradation and cha... more Osteoarthritis (OA) is the most common joint disease, characterized by matrix degradation and changes in chondrocyte morphology and metabolism. Literature reported that electromagnetic fields (EMFs) can produce benefits in OA patients, even if EMFs mechanism of action is debated. Human osteoarthritic chondrocytes isolated from femoral heads were cultured in vitro in bidimensional (2-D) flasks and in three-dimensional (3-D) alginate beads to mimic closely cartilage environment in vivo. Cells were exposed 30 min/day for 2 weeks to extremely low-frequency electromagnetic field (ELF) with fixed frequency (100 Hz) and to therapeutic application of musically modulated electromagnetic field (TAMMEF) with variable frequencies, intensities, and waveforms. Cell viability was measured at days 7 and 14, while healthy-cell density, heavily vacuolized (hv) cell density, and cluster density were measured by light microscopy only for 3-D cultures after treatments. Cell morphology was observed for 2-D and 3-D cultures by transmission electron microscopy (TEM). Chondrocyte exposure to TAMMEF enhances cell viability at days 7 and 14 compared to ELF. Light microscopy analysis showed that TAMMEF enhances healthy-cell density, reduces hv-cell density and clustering, compared to ELF. Furthermore, TEM analysis showed different morphology for 2-D (fibroblast-like) and 3-D (rounded shape) cultures, confirming light microscopy results. In conclusion, EMFs are effective and safe for OA chondrocytes. TAMMEF can positively interfere with OA chondrocytes representing an innovative non-pharmacological approach to treat OA.

Research paper thumbnail of Paraneoplastic necrotizing myopathy associated with adenocarcinoma of the lung – a rare entity with atypical onset: a case report

Journal of Medical Case Reports, 2013

Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recogni... more Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recognized paraneoplastic syndromes. However, paraneoplastic necrotizing myopathy is a more recently defined clinical entity, characterized by rapidly progressive, symmetrical, predominantly proximal muscle weakness with severe disability, and associated with a marked increase in serum muscle enzyme levels. Paraneoplastic necrotizing myopathy requires muscle biopsy for diagnosis, which typically shows massive necrosis of muscle fibers with limited or absent inflammatory infiltrates. Case presentation: We report the case of an 82-year-old Italian-born Caucasian man who was admitted to hospital because of heart failure and two drop attacks. Over the following days, he developed progressive severe weakness, dysphagia, and dysphonia. Testing showed increasing serum muscle enzyme levels. Electromyography showed irritative myopathy of the proximal muscles and sensorimotor polyneuropathy. Muscle biopsy (left vastus lateralis) showed massive necrosis of muscle fibers with negligible inflammatory infiltrates, complement membrane attack complex deposition on endomysial capillaries, and moderate upregulation of major histocompatibility complex-I. Computed tomography of the thorax showed a nodular mass in the apex of the right lung. The patient was diagnosed with paraneoplastic necrotizing myopathy. In spite of high-dose corticoid therapy, he died 1 month later because of his aggressive cancer. Subsequent electron microscopic examination of a muscle biopsy specimen showed thickened walls and typical pipestem changes of the endomysial capillaries, with swollen endothelial cells. Poorly differentiated adenocarcinoma of the lung was confirmed on post-mortem histological examination. Conclusions: Paraneoplastic necrotizing myopathy is a rare syndrome with outcomes ranging from fast progression to complete recovery. Treatment with corticosteroids is often ineffective, and prognosis depends mainly on the characteristics of the underlying cancer. This case shows that paraneoplastic necrotizing myopathy may have an atypical appearance, and should be considered in elderly patients with neoplastic disease. In this case, the diagnosis was delayed by the unusual clinical picture that suggested heart disease rather than muscle disease.

Research paper thumbnail of Human placenta and fetal membranes express nerve growth factor mRNA and protein

Journal of Endocrinological Investigation, 2006