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Introduction. In vitro data demonstrate that estrogens improve differentiation of myoblasts deriving from FSHD patients, counteracting muscle differentiation impairment caused by the homeobox protein DUX4. Objectives. We aim to assess in vivo estrogen activity on regenerative potential of muscle precursor cells (perivascular cells, PVCs) derived from healthy individuals and engineered to express DUX4, or derived from FSHD patients. Methods. Cherry-expressing PVCs were implanted into injured hindlimb-tibial muscle of NSG female mice treated with 17?-estradiol (E2) or fulvestrant. Animals were monitored by fluorescence emission and by functional treadmill test, and molecularly by IHC, gene and protein expression. Results: Human PVCs are able to participate to muscle regeneration of injured muscle. Preliminary data show that DUX4 reduces the performance of implanted PVCs whereas 17?-estradiol is able to recover it. Conclusions: These data indicate the usefulness of PVCs to study in vivo muscle differentiation of FSHD and suggest the potential protective function of estrogen.

Background: An important question behind vertebrate evolution is whether the cranial placodes originated de novo, or if their precursors were present in the ancestor of chordates. In this respect, tunicates are of particular interest as they are considered the closest relatives to vertebrates. They are also the only chordate group possessing species that reproduce both sexually and asexually, allowing both types of development to be studied to address whether embryonic pathways have been co-opted during budding to build the same structures. Results: We studied the expression of members of the transcriptional network associated with vertebrate placodal formation (Six, Eya, and FoxI) in the colonial tunicate Botryllus schlosseri. During both sexual and asexual development, each transcript is expressed in branchial fissures and in two discrete regions proposed to be homologues to groups of vertebrate placodes. Discussion: Results reinforce the idea that placode origin predates the origin of vertebrates and that the molecular network involving these genes was co-opted in the evolution of asexual reproduction. Considering that gill slit formation in deuterostomes is based on similar expression patterns, we discuss possible alternative evolutionary scenarios depicting gene co-option as critical step in placode and pharynx evolution. Developmental Dynamics 242:752-766, 2013. © 2013 Wiley Periodicals, Inc.

Invertebrate Survival Journal, Vol 13 No 1 (2016)

Aims: Diabetic encephalopathy (DE) down-regulates brain cholinergic activity that in turn controls proNGF release and maturation. Electroacupuncture (EA) modulates NGF system in experimental DE. We studied, in the hippocampus (HP) of diabetic rats, EA effects on: proNGF and M1AChR distribution; activity-dependent proNGF release; p75 neurotropin receptor (p75NTR) challenge by proNGF. Methods: DE was induced in young adult rats by streptozotocin (STZ). One week after STZ injection, low frequency EA was started and repeated twice a week for 3 weeks. At the end of the treatments, in HP from control, STZ and STZ/EA rats, we analyzed: the expression of proNGF and M1AChR and their co-localization with glutamatergic and GABAergic markers by confocal microscopy; proNGF isoforms release in slices superfused and stimulated by the muscarinic agonist carbachol (CCh), by Western blot and ELISA; different proNGF isoforms binding to the pro-apoptotic p75NTR, by co-immunoprecipitation. Results: STZ decreased and EA normalized the total cell number and the cells expressing M1AChR in HP tissue. proNGF and M1AChR colocalized with vGlut1 in HP cells. Activity-dependent proNGF release from HP slices increased in STZ rats, while EA counteracted the STZ effects. The enhancement of p75NTR interaction with the 25 kDa proNGF in diabetic brain was also counteracted by EA. Conclusions: EA is effective in restoring diabetes-induced alteration in M1AChR distribution in brain areas that produce and release proNGF. Diabetes affects and EA normalizes the production, release and activity of proNGF, suggesting a possible ability of EA in modulating the activity of cholinergic circuits.

32nd European Photovoltaic Solar Energy Conference and Exhibition; 1465-1469, The wider portfolio of today's available photovoltaic (PV) technologies on the market makes the measurement of the spectral content of the incoming sun or artificial light a key parameter for the characterization, calibration, and energy yield estimation of these devices. At present there is a growing request for harmonization of good measurement practices and for knowledge transfer in the field of spectrally resolved solar radiation for solar energy applications (e.g. photovoltaics) in order to make these measurements comparable and directly traceable to SI units. A group of European research institutes active in the PV field for research, characterization and engineering, set up the fifth comparison of spectroradiometers for solar spectrum measurements. In this paper the preliminary results of such exercise are reported.

Aims: It is emerging a correlation between diabetes and brain pathologies, such as Alzheimer's Disease (AD), associated with decreased synaptic plasticity and cholinergic dysfunctions. We investigated whether diabetes and electroacupuncture (EA), affecting cholinergic neurotransmission at septo-hippocampal terminals, could alterate dentate gyrus (DG) long-term potentiation (LTP). Methods: After induction of type 1 diabetes in rats by streptozotocin (STZ), EA was performed for 3 weeks starting 1 week after STZ treatment. We performed electrophysiological studies in DG by stimulating medial-perforant pathway. LTP was evoked by high-frequency stimulation (HFS) consisting of eight trains, each of eight stimuli at 200 Hz, and an inter-train interval of 2 s. The occurrence of LTP was studied in HP slices from controls, STZ and STZ+EA rats. The role of muscarinic modulation of LTP was investigated by carbachol (CCh) stimulation of HP slices. The specific role of M1 acetylcholine receptor (M1AChR) was studied by the M1-antagonist telenzepine (TZ) both in bath superfusion and in vivo. Results: Our results demonstrated an impairment of LTP in STZ rats compared to controls. EA restored LTP in STZ rats. CCh counteracted EA effects in HP from diabetic animals. TZ treatment of diabetic HP slices or diabetic animals in vivo also abolish EA effects on LTP. Conclusions: Our results suggest a possible role for EA in modulating LTP at DG, by acting on the regulation of cholinergic neurotransmission. Our data point to a M1AChR-mediated EA action. Therefore, EA could represent an useful tool for progressive cognitive decline associated with diabetes.

Aim: Diabetic Encephalopathy (DE) affects neurogenesis of the hippocampal (HP) subgranular zone (SGZ) probably dysregulating the neurotrophic proNGF/NGF system, whose activity is regulated by the cholinergic neurotransmission from medial septum (MS). Electroacupuncture (EA) is effective in modulating proNGF/NGF balance in DE rats. We studied the effects of EA on: SGZ neurogenesis; proNGF/mNGF content in HP tissues; NGF receptors (TrkA and p75NTR) distribution and activity, in the MS. Methods: DE was induced in young adult rats by streptozotocin (STZ). One week after STZ, low-frequency EA treatment was started and repeated twice a week for 3 weeks. We analyzed in ctr, STZ and STZ+EA rats: the number of doublecortin (DCX)-positive cells in SGZ by confocal microscopy; the mNGF/proNGF in HP by ELISA; the colocalization of choline acetyltransferase (ChAT) and p75NTR or TrkA in MS by confocal microscopy; the activation of p75NTR pro-apoptotic signaling in MS by Western blot for the JNK/pospho-JNK. Results: SGZ neurogenesis, measured as number of DCX-positive cells, was decreased by STZ and normalized by EA. The STZ-alterated proNGF/mNGF ratio in HP was also normalized by EA. The number of cells immunopositive for ChAT and p75NTR or TrkA in MS were decreased after STZ, while EA restored control levels. In MS, EA counteracted the STZ increase of JNK phosphorylation, index of p75NTR-mediated pro-apoptotic activation. Conclusions: EA counteracts the effects of diabetes on hippocampal neurogenesis, apoptosis and neurotrophins metabolism. Thus, such physical therapy could be useful in contrasting the development of cellular and molecular correlates of diabetes-induced cognitive decline.

We present the results of the analysis of deep archival \sat\ observations towards the dwarf spheroidal galaxies Draco, Leo I, Ursa Major II and Ursa Minor in the Milky Way neighbourhood. The X-ray source population is characterized and cross-correlated with available databases with the aim to infer their nature. We also investigate if intermediate-mass black holes are hosted in the center of these galaxies. In the case of Draco, we detect 96 high-energy sources, two of them being possibly local stars, while no evidence for any X-ray emitting central compact object is found. Towards the Leo I and UMa II field of view we reveal 116 and 49 X-ray sources, respectively. None of them correlates with the putative central black holes and only one is likely associated with a UMa II local source. The study of the UMi dwarf galaxy shows 54 high-energy sources and a possible association {with a source at the dSph center}. We put an upper limit to the central compact object luminosity of 4.02$\times$10$^{33}$ erg/s. Furthermore, via the correlation with a radio source near the galactic center, we get that the putative black hole should have a mass of $\left(2.76^{+32.00}_{-2.54}\right)\times10^6 M_{\odot}$ and be radiatively inefficient. This confirms a previous result obtained by using Chandra data alone., MNRAS, in press, tables available on line

Roberto Pazzi, Domani sarò re, Milano: Longanesi, 1997.

Sebastiano Vassalli, La notte del lupo, Milano, Baldini e Castoldi, 1998, 182 pp. Lire 24.000.

31st European Photovoltaic Solar Energy Conference and Exhibition; 1946-1951, Spectral tuning of solar simulators is a well-known procedure, used in the experimental practice for years with multi-junction cells for concentrating photovoltaics (CPV) and space photovoltaic (PV) applications. Multi-junction structures are also used in second generation thin-film PV modules (for example in a-Si:H compounds). A dedicated international standard procedure (IEC 60904-1.1) is in view of publication, describing the “how-to” for current-voltage characterization of multi-junction PV cells and modules: thereafter spectral tuning will need to become soon a widely diffuse practice in research, research-and-development and development-andproduction sites. With this in mind, the authors present here the upgrade of a Class AAA large area pulsed solar simulator to allow spectral tuning by means of a set of high power LEDs. They revise the spectral tuning procedure and show results on commercial modules. They give indications to quantify the new uncertainty contributions arising from the non-uniformity of spectral irradiance and from the spectral mismatch, which affects not only the shortcircuit current (which is the same as in single-junction devices), but also the fill factor and the open-circuit voltage in multi-junction devices.

31st European Photovoltaic Solar Energy Conference and Exhibition; 2444-2448, In this work, we present a comprehensive protocol for the assessment of the quality of the lamination/encapsulation process of CIGSS thin film glass/glass solar PV modules. The quality protocol includes: (1) a polymerization test, (2) optical characterization (3) a mechanical adhesion test, and (4) and climatic stresses (dampheat DH). In this contribution we apply the quality protocol to a set of lamination trials performed with EVA (with and without the presence of an edge-sealant) and with modifications to the standard curing recipe (i.e. shorter curing time, lower curing temperature). The execution of DH tests on the prototypes laminated with EVA shows that the durability to moisture ingress for the device laminated with EVA and no sealant is guaranteed up to 1000 h (enough to pass a conventional IEC 61646 test), but is followed by a severe degradation after prolonged exposures in DH. All devices laminated with EVA and the addition of an edge sealant exhibited an excellent resistance to exposure in DH also for prolonged periods up to 5538 h. By combining the different outcomes of the protocol for quality and considering the different lamination processes, we conclude that a reduction of curing time from 11 to 7 min (at constant temperature: 145°C), apparently has nearly no effect on the quality of the lamination process. On the other hand, the low temperature process (120°C, 11 min) has a strongly reduced gel content, which consequently reduces the adhesion strength of the device. The low temperature process should be avoided.

BACKGROUND: Neurotrophic factors, such as Nerve Growth Factor (NGF), play a key role in the stimulation of sprouting, synaptic plasticity, and reorganization after spinal cord damage. AIM: The aim of this study was to investigate the expression of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) of newborns with myelomeningocele (MMC) and to determine its correlation with this spinal malformation. PATIENTS AND METHODS: To measure the expression of NGF, we collected CSF samples of 14 newborns with MMC taken immediately before the neurosurgical correction of the spinal malformation and of 14 matched controls. Endogenous NGF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. RESULTS: In the CSF of patients with MMC, NGF levels showed a significant increase compared to the mean levels of the control group (63.05 ± 7.3 vs 18.32 ± 4.5 pg/mL; (p < 0.001). No correlation was found between NGF expression and different types of MMC malformation, such as the level of spinal lesion and the association with Chiari II syndrome. CONCLUSIONS: Our study shows an over-expression of NGF in the CSF of newborns with MMC. The observed pattern of NGF up-regulation in this subset of patients may stimulate axonal sprouting and synaptic reorganization of the damaged neural cells at the site of spinal cord injury, thereby representing an important biochemical marker of spinal cord damage in MMC patients.

Background: To date, no specific therapy is available for optic pathway glioma (OPG)-associated visual impairment. The aim of this study was to evaluate the effects on visual function of murine nerve growth factor (NGF) eye drop administration in patients with visual impairment due to OPGs. Methods: A prospective randomized double-blind controlled study was conducted in patients younger than 24 years with OPG-induced visual impairment, without or with NF1. All patients were off-therapy and with stable disease at 2 brain magnetic resonance imaging (MRI) controls, performed at least 6 months apart. NGF eye-drop was prepared by Policlinico Gemelli University Pharmacy according to standard required for human use. The patients were assessed by clinical evaluation and ophthalmological examinations including visual acuity, visual field, photopic negative response (PhNR), visual evoked potentials (PEV), Ganzfeld electroretinograms and optic coherence tomography. All patients were recorded at baseline and 15, 30, and 90 days post treatment. A further evaluation at 180 days is planned but no data are available at this time. Brain MRI was performed at baseline and is planned at 180 days after NGF treatment. All the evaluations were performed by considering the change of parameters values from baseline. Results: Ten and 8 patients received a single 10-day course of 1mg murine NGF topical administration and placebo, respectively. Preliminary results (up to 90 days) showed a 40% (p=0.02) and a 50% (p=0.09) improvement of visual field in at least one eye from the baseline evaluations with a better quality of life in the NGF group at 30 and at 90 days post treatment, respectively, compared to a 14% increase in the placebo group. An increase of the mean PhNR amplitude till 90 days was observed in the treated eyes but this was not statistically significant compared to the placebo group; mean PhNR latency increased significantly compared to the placebo group (1.3 vs -1.8 p=0.03) at 15 days but then the difference disappeared. Mean PEV amplitude increase was borderline significant compared to placebo group (p=0.06) at 30 days. No changes in the visual acuity were observed in both groups and no other significant differences were observed for the other ophthalmological examinations. Conclusions: Preliminary results suggest a visual rescuing mechanism exerted by murine NGF on the residual viable optic pathways. NGF administration appears an effective and safe adjunct therapy in patients with OPG-associated visual impairment. No conflict of interest.

Diabetes has been associated with dysfunctions and degeneration of basal forebrain cholinergic neurons (BFCN) that could depend upon defective nerve growth factor (NGF) utilization and incorrect activity-dependent maturation of the precursor ProNGF into mature NGF, with subsequent activation of apoptotic signaling. Electro-acupuncture (EA) could improve brain NGF availability and utilization. We hypothesized that EA could counteract the development of diabetes-associated cholinergic dysfunctions by regulating endogenous brain NGF maturation and utilization. We used the streptozotocin (STZ) model of type 1 diabetes in young adult rats and assessed the early variations of ProNGF/NGF in the cortex and hippocampus, as well as the features of ProNGF/NGF signaling in the BFCN following STZ and EA at St36. Four weeks after diabetes induction the ProNGF/NGF ratio was increased in the cortex and hippocampus while the pro-apoptotic c-Jun N-terminal kinase (JNK) signaling, associated with p75NTR receptor activation by ProNGF, was increased in the BFCN. EA counteracted the diabetes-induced deregulation of ProNGF/NGF ratio, de-activated JNK, increased tyrosine kinase-A (TrkA) receptor, Akt and extracellular signal-regulated kinases (ERK) phosphorylation. Our data, suggesting a possible beneficial effect of EA on brain cholinergic system in diabetes, indicate that the regulation of neurotrophins' expression and activity is one of the possible neurophysiological mechanism underlying acupuncture's effects on brain neurons.

Recent data indicate that age-related N-methyl-d-aspartate receptor (NMDAR) transmission impairment is correlated with the reduction in serine racemase (SR) expression and d-serine content. As apoptosis is associated with several diseases and conditions that generally occur with age, we investigated the modulation of SR/d-serine pathway during neuronal apoptosis and its impact on survival. We found that in cerebellar granule neurons (CGNs), undergoing apoptosis SR/d-serine pathway is crucially regulated. In the early phase of apoptosis, the expression of SR is reduced, both at the protein and RNA level through pathways, upstream of caspase activation, involving ubiquitin proteasome system (UPS) and c-Jun N-terminal kinases (JNKs). Forced expression of SR, together with treatment with NMDA and d-serine, blocks neuronal death, whereas pharmacological inhibition and Sh-RNA-mediated suppression of endogenous SR exacerbate neuronal death. In the late phase of apoptosis, the increased expression of SR contribute to the last, NMDAR-mediated, wave of cell death. These findings are relevant to our understanding of neuronal apoptosis and NMDAR activity regulation, raising further questions as to the role of SR/d-serine in those neuro-pathophysiological processes, such as aging and neurodegenerative diseases characterized by a convergence of apoptotic mechanisms and NMDAR dysfunction.

The nerve growth factor (NGF) is a neurotrophin regulating the survival and function peripheral sensory and sympathetic neurons and of forebrain cholinergic neurons. Both peripheral neuropathies and brain cholinergic dysfunctions could benefit from NGFbased therapies, but the clinical use of NGF has been so far hampered by the development of important side effects, like hyperalgesia and autonomic dysfunctions. Acupuncture is a therapeutic technique and is a part of traditional Chinese medicine. Western descriptions of the clinical efficacy of acupuncture on pain, inflammation, motor dysfunction, mood disorders, and seizures are based on the stimulation of several classes of sensory afferent fibers and the consequent activation of physiological processes similar to those resulting from physical exercise or deep massage. Recently, it has been shown that peripheral sensory stimulation by electroacupuncture (EA) could improve brain NGF availability and utilization, at the same time counteracting the major sideeffects induced by NGF administration. This review focuses on the emerging links between EA and NGF with special emphasis on the work carried out in the last decade in our laboratory, investigating the role of NGF as a mediator of EA effects in the central nervous system and as a modulator of sensory and autonomic activity.

Background: Type 1 diabetes (DB) is a multifactorial metabolic disorder characterized by loss of insulin-producing pancreatic ß-cells, and metabolic and functional deficits in a number of cells, including kidney cells. Nerve growth factor (NGF) is a signaling molecule that is up-regulated in cells affected by diabetes-linked disorders. However, whether DB alters the expression of NGF in the kidney is not known. Methods: DB was induced in adult male rats with a single injection of streptozotocin (STZ), and NGF protein levels were analyzed in a time-course study in serum and kidney. The expression of NGF receptors in the kidneys of healthy and DB rats was evaluated by immunohistochemistry. NGF levels as well as apoptotic features in the kidneys of healthy rats injected with purified NGF were also assessed. Results: This study revealed that DB elevates NGF levels in serum and NGF expression in the kidney and that subcutaneous administration of NGF causes a marked uptake of NGF in kidney cells. The elevated presence of NGF in kidney cells is not associated with proapoptotic factor expression. Conclusions: The present data suggest that NGF presence in the kidney might play a survival, and most probably protective, role in kidney cells.

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls.

Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma.

BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. METHODS: In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of alpha1a-, alpha1b-, alpha1d-, and beta2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). RESULTS: It was found that EV injection results in significantly higher mRNA expression of ovarian alpha1b- and alpha1d-AR in PCO rats compared to control rats. The p75NTR and beta2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of beta2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of alpha1a-, alpha1b- and alpha1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for alpha1b-AR. CONCLUSION: The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.

The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as NGF, BDNF, leptin and MC may be involved in the development of cardiovascular disease and related disorders.

Previous studies on the effect of repeated electro-acupuncture (EA) treatments in rats with steriod-induced polycystic ovaries (PCO), EA has been shown to modulate nerve growth factor (NGF) concentration in the ovaries as well as corticotropin releasing factor (CRF) in the median eminence (ME). In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1), a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p < 0.05). In the hypothalamus, however, ET-1 concentrations were found to be significantly higher in the PCO group receiving EA than in the healthy control group (p < 0.05). Concentrations of ovarian NGF protein were significantly higher in the PCO control group compared with the healthy control group (p < 0.001), and these concentrations decreased significantly after repeated EA treatments compared with those in the PCO control group (p < 0.05) and were found to be the same as those in the healthy control group. In conclusion, these results indicate that EA modulates the neuroendocrinological state of the ovaries, most likely by modulating the sympathetic nerve activity in the ovaries, which may be a factor in the maintenance of steroid-induced PCO.

Aim of this study was to investigate the synthesis, release and effects of nerve growth factor (NGF) in human synovial cells isolated from synovial tissue specimen from healthy and osteoarthritis (OA) patients. METHODS: Human synovial fibroblasts cultures were established starting from healthy and osteoarthritis patients. NGF protein levels in the culture medium, NGFmRNA and high-affinity NGF receptor (Tyrosine kinase A: TrkA) expression in the cells were evaluated in basal conditions and after stimulation with pro-inflammatory cytokines or with the neuropeptide cholecystokinin-8 (CCK-8). The effect of NGF supplement to culture medium on cell proliferation, TrkA expression, and tumour necrosis factor-alpha (TNF-alpha) and inducible-nitric oxide synthase (iNOS) production was investigated. RESULTS: Under basal conditions human synovial cells produce and release NGF. Both interleukin-1-beta (IL-1 beta) and TNF-alpha, but not CCK-8 promote NGF synthesis and release from OA cells. TrkA NGF receptors are also expressed in both normal and OA synovial cells. NGF, but not IL-1 beta, TNF-alpha and CCK-8, enhances the expression of TrkA in isolated synovial cells. NGF down-regulates IL-1 beta-induced TNF-alpha and iNOS production by OA synovial fibroblasts. CONCLUSIONS: NGF is produced and released and TrkA receptors are expressed in synovial inflammation. Overexpression of NGF in inflammed joints might be involved in the modulation rather than in the induction of the joint inflammatory response.

A recent clinical report demonstrated that topical nerve growth factor (NGF) treatment in patients affected by corneal neurotrophic ulcers induced epithelial and stromal healing restoring corneal integrity. Mechanisms(s) undergoing these clinical NGF actions are still unclear. The aim of this study was to investigate the role of NGF in human and rat cornea physiopathology.Expression of high-affinity NGF receptors, NGF-mRNA, and NGF protein was evaluated in human and rat normal corneas, in human and rat corneal epithelial cell cultures, in human corneal organ culture, and in the rat cornea after an experimental model of epithelial injury, by means of immunohistochemistry, in situ hybridization reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay.The resultant data demonstrated that NGF is a constitutive molecule present and produced in normal human and rat corneas. In vitro human and rat corneal epithelial cells produce, store, and release NGF and also express high-affinity NGF receptors (TrkA). In human organ culture, epithelium, keratocytes, and endothelium have been shown to bind exogenous radiolabeled NGF, and the epithelial cells' binding was increased after epithelium injury. In vivo, after rat corneal epithelial injury, a transient increase of corneal NGF levels was observed. Inhibition of endogenous NGF activity by neutralizing anti-NGF antibodies delayed the corneal epithelial healing rate, whereas exogenous administration of NGF accelerated healing.Taken together, the above findings show that NGF plays an important role in corneal physiopathology and suggest that this neurotrophin may exert therapeutic action in wide-spectrum corneal diseases.

V1180 Cas is a young variable that has shown strong photometric fluctuations (Delta_I~6mag) in the recent past, which have been attributed to events of enhanced accretion. The source has entered a new high-brightness state in Sept.2013, which we have previously analyzed through optical and near-IR spectroscopy. To investigate the current active phase of V1180 Cas, we performed observations with the Chandra satellite to study the X-ray emission from the object and its connection to accretion episodes. Chandra observations were performed in early Aug.2014. Complementary JHK photometry and J-band spectra were taken at our Campo Imperatore facility to relate the X-ray and near-IR emission from the target. We observe a peak of X-ray emission at the nominal position of V1180 Cas. This signal corresponds to an X-ray luminosity L_X(0.5-7 kev) in the range 0.8-2.2e30 erg/s. Based on the relatively short duration of the dim states in the light curve and on stellar luminosity considerations, we explored the possibility that the brightness minima of V1180 Cas are driven by extinction variations. From the analysis of the spectral energy distribution of the high state we infer a stellar luminosity of 0.8-0.9 Lsun and find that the derived L_X is comparable to the average X-ray luminosities of T Tauri stars. Moreover, the X-ray luminosity is lower than the X-ray emission levels of 5e30 -1e31 erg/s detected at outbursts in similar low-mass objects. Our analysis suggests that at least part of the photometric fluctuations of V1180 Cas might be extinction effects rather than the result of accretion excess emission. However, as the source displays spectral features indicative of active accretion, we speculate that its photometric variations might be the result of a combination of accretion-induced and extinction-driven effects, as suggested for other young variables, such as V1184 Tau and V2492 Cyg., Comment: 6 pages, 5 figures, accepted by A&A

Aim of this study was to investigate the synthesis, release and effects of nerve growth factor (NGF) in human synovial cells isolated from synovial tissue specimen from healthy and osteoarthritis (OA) patients.Human synovial fibroblasts cultures were established starting from healthy and osteoarthritis patients. NGF protein levels in the culture medium, NGFmRNA and high-affinity NGF receptor (Tyrosine kinase A: TrkA) expression in the cells were evaluated in basal conditions and after stimulation with pro-inflammatory cytokines or with the neuropeptide cholecystokinin-8 (CCK-8). The effect of NGF supplement to culture medium on cell proliferation, TrkA expression, and tumour necrosis factor-alpha (TNF-alpha) and inducible-nitric oxide synthase (iNOS) production was investigated.Under basal conditions human synovial cells produce and release NGF. Both interleukin-1-beta (IL-1 beta) and TNF-alpha, but not CCK-8 promote NGF synthesis and release from OA cells. TrkA NGF receptors are also expressed in both normal and OA synovial cells. NGF, but not IL-1 beta, TNF-alpha and CCK-8, enhances the expression of TrkA in isolated synovial cells. NGF down-regulates IL-1 beta-induced TNF-alpha and iNOS production by OA synovial fibroblasts.NGF is produced and released and TrkA receptors are expressed in synovial inflammation. Overexpression of NGF in inflammed joints might be involved in the modulation rather than in the induction of the joint inflammatory response.

PURPOSE: To determine the presence of nerve growth factor (NGF), NGF mRNA, and NGF receptor (TrkA) in rabbit ocular tissues, and whether changes occur in NGF and NGF mRNA levels after experimental iridectomy. METHODS: Immunohistochemistry for NGF and TrkA and in situ hybridization for NGF mRNA were performed on rabbit cornea, iris, ciliary body, and lens in the basal state. Quantification of NGF mRNA and NGF protein levels in these tissues was performed by RT-PCR and immunoenzymatic assay, respectively. A time course of NGF concentration in the aqueous humor and the expression of NGF mRNA in iris and ciliary body were performed after the iridectomy and were compared with levels in a sham-treated group (paracentesis). RESULTS: Cornea, iris, ciliary body, and lens expressed NGF mRNA, NGF protein, and TrkA in the basal state. The highest levels of NGF were detected in the iris (8938.0 +/- 3968.1 pg/g), and the lowest were in the aqueous humor (22.8 +/- 9.7 pg/mL). Experimental iridectomy induced a transient increase of NGF concentration in the aqueous humor that reached its peak 4 hours after the experimental injury (464.4 +/- 29.9 pg/mL versus the control group 101.6 +/- 18.8 pg/mL; P < 0.001) and returned to baseline value after 7 days. A significant increase of NGF mRNA was also observed 1 hour and 4 hours after the iridectomy in the iris (1 hour, 788 +/- 85 OD; 4 hours, 760 +/- 81 OD versus baseline, 246 +/- 32 OD; P < 0.0001) and ciliary body (1 hour, 330 +/- 19 OD; 4 hours, 453 +/- 52 OD versus baseline, 219 +/- 37 OD; P < 0.05), but not in the cornea, lens, or any tissues from the control group. CONCLUSIONS: NGF is present and produced in the anterior segment of the eye and is released in the aqueous humor in the basal state. Experimental iridectomy induces increased production of NGF in the iris and in the ciliary body and an increased concentration of NGF in the aqueous humor.

Nerve growth factor (NGF) is a neurotrophic and immunomodulatory factor contributing of the control of cutaneous morphogenesis, wound healing and inflammatory responses. Following the evidence that topical administration of NGF leads to healing of human corneal ulcers, we investigate the therapeutic action of NGF on immune and/or autoimmune cutaneous ulcers. We found that 1-10 micrograms of highly purified murine NGF dissolved in 50 microliters of physiological solution and topically applied to skin ulcer leads, after 4-12 weeks of daily treatment (depending on the size and depth of the lesion) to complete healing of the ulcer. Thus, NGF was able to promote complete repair in human skin and corneal ulcers which were poorly or non-responsive to conventional topical and systemic treatments. No side effects were observed and a follow up after 4 months showed no signs of relapse. These findings indicate that failure of cutaneous tissues to produce sufficient amounts of NGF might represent a prominent mechanism implicated in the clinical manifestation of ocular ulcers.

Carbon nanotubes (CNTs) are currently under active investigation for their use in several biomedical applications, especially in neurological diseases and nervous system injury due to their electrochemical properties. Nowadays, no CNT-based therapeutic products for internal use appear to be close to the market, due to the still limited knowledge on their fate after delivery to living organisms and, in particular, on their toxicological profile. The purpose of the present work was to address the distribution in the brain parenchyma of two intranasally delivered MWCNTs (MWCNTs 1 and a-MWCNTs 2), different from each other, the first being non electroconductive while the second results in being electroconductive. After intranasal delivery, the presence of CNTs was investigated in several brain areas, discriminating the specific cell types involved in the CNT uptake. We also aimed to verify the neuroprotective potential of the two types of CNTs, delivering them in rats affected by early diabetic encephalopathy and analysing the modulation of nerve growth factor metabolism and the effects of CNTs on the neuronal and glial phenotypes. Our findings showed that both CNT types, when intranasally delivered, reached numerous brain areas and, in particular, the limbic area that plays a crucial role in the development and progression of major neurodegenerative diseases. Furthermore, we demonstrated that electroconductive MWCNTs were able to exert neuroprotective effects through the modulation of a key neurotrophic factor and probably the improvement of neurodegeneration-related gliosis.