Type 1 diabetes is an autoimmune disease that is accompanied by an immune response against pancreatic cells. As gangliosides are expressed in both peripheral nerves and pancreatic cells, we examined ...the possibility of correlation between type 1 diabetes, anti‐ganglioside autoantibodies, and neuropathy. Fifty diabetic patients and 30 controls with other autoimmune diseases underwent neurological examination and search for antibodies to gangliosides, glutamic acid decarboxylase (GAD65), and tyrosine phosphatase (IA2). Sixteen (32%) diabetic patients had neuropathy. Twelve diabetic sera were found to have anti‐ganglioside autoantibodies. Twenty sera were positive for anti‐GAD65 and nine for anti‐IA2 antibody. Sera from three control patients had anti‐ganglioside autoantibodies. No significant correlation was found between autoantibodies, neuropathy, and disease duration. Disease duration was shorter in patients with antibodies to GAD65 and IA2 and longer in neuropathic patients. The higher prevalence of antibodies in diabetic patients compared to controls may reflect the common pattern of antigens shared by peripheral nerve and pancreatic islet cells. Muscle Nerve, 2009
Background: About 2.5% of patients with idiopathic peripheral neuropathy or idiopathic dysautonomia have underlying celiac disease (CD). Antibodies to ganglioside have been reported in CD patients ...with neuropathy. No data are so far available on the presence in CD of acetylcholine receptor (AChR) antibodies. Muscle AChR antibodies are found in patients with myasthenia gravis, and ganglionic AChR antibodies in patients with autoimmune autonomic neuropathy.
Objective: To determine the frequency of AChR antibodies in CD patients and assess possible correlations with neurological manifestations.
Methods: Seventy CD patients (16 M, 54 F, mean age 36 years) underwent neurological and electrophysiological evaluation. AChR antibodies were detected with radioimmunoprecipitation assay. Sera from 15 age-matched patients with systemic lupus erythematosus (SLE) and 10 with Sjogren syndrome were studied as controls.
Results: None of our CD patients complained of autonomic symptoms or fatigable weakness. Borderline titres (0.03-0.05 nmol/l) of ganglionic AChR antibodies were present in 4 patients, one affected with type I diabetes and one with subclinical neuropathy. Three of the 4 patients underwent cardiovascular autonomic function tests, which showed no abnormalities. Low levels of ganglionic AChR antibodies (0.05-0.10 nmol/l) were found in 2 SLE control patients, one of whom had a severe sicca complex. Muscle AChR antibodies (>1.0 nmol/l) were found in two CD patient and one control patient with SLE. Neither had symptoms or signs of myasthenia gravis.
Discussion and conclusions: CD is occasionally associated with neurologic disease, and with antibody reactivity to neuronal antigens. None of our CD patients had autonomic failure or significant levels of ganglionic AChR antibodies. Two CD patient and one control with SLE had muscle AChR antibodies without clinical evidence of myasthenia. The presence of antibodies in CD and in SLE patients may reflect a non-specific autoimmune response in these patients or may indicate subclinical autoimmune autonomic and neuromuscular involvement.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Endothelial dysfunction is crucial in Behçet's disease (BD) pathogenesis, and measures of endothelial damage are potential markers of BD activity. Heparan sulfate (HS) is the most abundant ...proteoglycan in the endothelial cells, and anti-HS antibodies have been reported in subjects with vascular damage, due to vasculitis/vasculopathy. The aim of our study was to measure serum anti-HS antibodies in patients with BD and to determine whether their presence correlates with disease activity or clinical manifestations.
Thirty-two patients with BD (21 men, 11 women) (median age 36.81+/-12.0 years) were considered. Of these, 13 had clinically active disease at the time of study. The mean disease duration was 7.31+/- 8.2 years (median 6 years). Anti-HS antibodies were measured by ELISA. As controls, sera from 40 sex- and age-matched healthy subjects, and 78 age-matched patients with systemic lupus erythematosus (SLE) were studied.
Anti-HS IgM antibody titres were significantly higher in BD patients compared to healthy subjects (p=0.016) and SLE controls (p=0.0008). No differences in anti-HS IgG antibody titres were observed among the 3 groups. Using categorical data, increased titres of IgM anti-HS antibodies were significantly more frequent in patients with BD vs patients with SLE (p=0.02). The presence of the antibodies, of either isotype, did not correlate with disease duration, disease activity or clinical manifestations.
BD patients have increased IgM anti-HS antibody titres compared to healthy and SLE controls. These antibodies did not correlate with disease activity or discrete clinical features, but might be relevant for pathogenic mechanisms of the disease.
Study was performed in Fischer-344 rats to test the effects of the intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely ...hypoxic rats. General and local anesthetics (isoflurane, N
20 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N
2O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg.kg
−1.h
−1 respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. During the last 20 min Pa
O2 was lowered to 15–20 mmHg. Pa
co2 was maintained between 35–40 mmHg, rectal temperature at 37 °C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen
in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 21 and 18 (
μol
g
in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg-kg
−1-h
−1 significantly reduced those adverse effects of hypoxia.
In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)
1A agonist ...8-hydroxy-2(di-
N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic
14C2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT
1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT
1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT
1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D
2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone. In summary, this study suggests that buspirone produces dual, dose-dependent rCMRglc effects: (i) at a low dose rCMRglc reductions in limbic areas and raphe nuclei, probably due to preferential activation of 5-HT
1A receptors, and (ii) at higher doses widespread rCMRglc reductions along with a rCMRglc increase in the lateral habenula resulting from dopamine D
2 receptor blockade.
•Abandoned olive groves were classified using machine learning and remote sensing.•A smartphone app was developed for collecting field samples to train the model.•A web-tool was developed to support ...the monitoring of land abandonment.
The abandonment of rural areas is an important environmental and socio-economic issue in Europe, threatening the stability and profitability of agricultural production. The identification and quantification of abandoned land is key for temporal and spatial monitoring of the process and for applying alternative management measures. Italy is one of the most important European countries for the production of high quality olive oil, accounting for a large slice of the current certificated production (i.e., PDO, PGI). In this study, we present a machine learning model (i.e., Random Forest) for the identification of abandoned olive tree groves using field observations and NDVI time series, tested in a typical agroecosystem in central Italy dominated by olive groves. An application for smartphones able to record the geographic position was developed and used to collect field points, which in turn were utilised to train the model. The data of NDVI from January to December 2020, calculated on Sentinel-2 images, were extracted for each monitoring point and gap-filled to obtain a 10-days interval time series. The Random Forest model used the annual NDVI time series as features and classified the sampling points in the test dataset with an accuracy of 0.85. The model showed a higher capacity of classifying cultivated than abandoned points, sensitivity being equal to 0.88 and specificity equal to 0.82. Results demonstrated the applicability of the combined approach for discriminating cultivated from abandoned olive tree groves, in case that the parcels destined for olive tree cultivation are known. A web-based tool was implemented to support land monitoring and management.
Mutations in LRRK2 gene cause inherited Parkinson's disease (PD) and variations around LRRK2 act as risk factor for disease. Similar to sporadic disease, LRRK2-linked cases show late onset and, ...typically, the presence of proteinaceous inclusions named Lewy bodies (LBs) in neurons. Recently, defects on ceramide (Cer) metabolism have been recognized in PD. In particular, heterozygous mutations in the gene encoding for glucocerebrosidase (GBA1), a lysosomal enzyme converting glucosyl-ceramides (Glc-Cer) into Cer, increase the risk of developing PD. Although several studies have linked LRRK2 with membrane-related processes and autophagic-lysosomal pathway regulation, whether this protein impinges on the Cer pathway has not been addressed. Here, using a targeted lipidomics approach, we report an altered sphingolipid composition in Lrrk2−/− mouse brains. In particular, we observe a significant increase of Cer levels in Lrrk2−/− mice and direct effects on GBA1. Collectively, our results suggest a link between LRRK2 and Cer metabolism, providing new insights into the possible role of this protein in sphingolipids metabolism, with implications for PD therapeutics.
•LRRK2 depletion impacts on sphingolipids metabolism.•Depletion of LRRK2 in mice brain affect GBA1 level and activity.•Cer are accumulated in lrrk2−/− mice brain.
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