Antinuclear antibodies in Frontotemporal Dementia: the tip's of autoimmunity iceberg?

Recent studies suggest a role of the autoimmune system dysregulation in Frontotemporal dementia (FTD). In the present study, we performed a broad immunological screening in a large sample of sporadic FTD patients. We reported a significant increase of antinuclear autoantibodies (ANA) positivity in 100 FTD patients as compared to 100 healthy controls (HC) (60% vs. 13%, p < .001). In FTD, ANA-positive and ANA-negative patients did not differ for any clinical feature. These data extend and further confirm autoimmune dysregulation in FTD. However, it still remains to be clarified whether these antibodies have a potential pathogenic role or represent simply an epiphenomenon.

Publisher Correction: Anti-AMPA GluA3 antibodies in Frontotemporal dementia: a new molecular target.

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Anti-AMPA GluA3 antibodies in Frontotemporal dementia: a new molecular target.

Frontotemporal Dementia (FTD) is a neurodegenerative disorder mainly characterised by Tau or TDP43 inclusions. A co-autoimmune aetiology has been hypothesised. In this study, we aimed at defining the pathogenetic role of anti-AMPA GluA3 antibodies in FTD. Serum and cerebrospinal fluid (CSF) anti-GluA3 antibody dosage was carried out and the effect of CSF with and without anti-GluA3 antibodies was tested in rat hippocampal neuronal primary cultures and in differentiated neurons from human induced pluripotent stem cells (hiPSCs). TDP43 and Tau expression in hiPSCs exposed to CSF was assayed. Forty-one out of 175 screened FTD sera were positive for the presence of anti-GluA3 antibodies (23.4%). FTD patients with anti-GluA3 antibodies more often presented presenile onset, behavioural variant FTD with bitemporal atrophy. Incubation of rat hippocampal neuronal primary cultures with CSF with anti-GluA3 antibodies led to a decrease of GluA3 subunit synaptic localization of the AMPA receptor (AMPAR) and loss of dendritic spines. These results were confirmed in differentiated neurons from hiPSCs, with a significant reduction of the GluA3 subunit in the postsynaptic fraction along with increased levels of neuronal Tau. In conclusion, autoimmune mechanism might represent a new potentially treatable target in FTD and might open new lights in the disease underpinnings.

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy.

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).

[Studies of the microbial content of raw materials used in pharmaceutical preparations]. / Ricerche sul contenuto microbico di materie prime impiegate nelle preparazioni farmaceutiche.

The microbiological controls (determination of the total and mycetic bacterial count; isolation of enterococci, Clostridium, Pseudomonas aeruginosa, Staph. aureus, E. coli, Salmonella and other Enterobacteriaceae) executed on 1517 samples of 100 varous raw materials, have ascertained the presence of a microbial contamination varying to matters, with presence also of pathogenic or hygienically undesirable microrganisms. The more contaminated substances have resulted to be those organic either of vegetable or animal origin. Sensible differences have been noted between the various lots and according to the various suppliers. The conservation trials under various conditions of temperature (15-22-37 degrees C) and humidity (30 degrees - 60 degrees - 90 degrees of relative humidity) with opened or closed recipients, have demonstrated the possibility of remarkable increases of the number of the microrganisms in the raw materials with increase of temperature and humitidy, especially in the non hermatically closed recipients.

[Prevention of post-ERCP acute pancreatitis with octreotide]. / Profilassi della pancreatite acute post ERCP con octreotide.

Acute pancreatitis is one of the most serious complications in endoscopic cholangio-pancreatography (ERCP) and endoscopic sphincterotomy (EPT). Many attempts to avoid such complication have proved to be unsuccessful. The aim of this study was to evaluate the therapeutic effect of octreotide acetate in preventing acute pancreatitis following ERCP. The study was carried out over 100 patients, randomly allocated in two groups. The first group of patients (50 pt.) received 0.1 mg of octreotide acetate s.c. 45 minutes before the ERCP, followed by another dose given 6 hours later. The second group received placebo s.c.

[Muco-purulent cervicitis: a frequent but little-known pathology. Clinical and laboratory considerations]. / La cervicite mucopurulenta: una patologia frequente ma poco conosciuta. Considerazioni cliniche e di laboratorio.

In order to assess the frequency of cervicitis, to investigate its aetiological causes and to open the debate upon this subject, the authors examined 144 not hospitalized women aging between 18 and 47. They were all in their fertile period and not pregnant. The diagnosis of MPC was given on the basis of the evaluation of the number of polymorphonuclear leukocytes (PNL) found on the endocervical smears, which had been previously coloured by the Gram method: the patients with an average number of PNL greater than 10 per microscopical field at a magnification of 1,000 were considered suffering from MPC, while those with a number of PNL less than 10 formed a group of control. Statistical methods were applied to the two different groups to verify the existence of any relationship between clinical, anamnestic and microbiologic features and MPC. The two groups were compared even after excluding those patients with a presence of Trichomonas vaginalis or yeasts and those suffering from bacterial vaginosis (BV). No significant relationship was found between the isolated microorganisms and MPC, while BV turned out to be related negatively. The objective signs of ectopia and erythema and the pH of the vaginal secretion turned out to be related significantly only after excluding from the selection those patients with a vaginal pathology, while including them, the association turned out to be significant only as to ectopia. The authors point out that: a) MPC represents the most frequent clinical condition; b) the greater part of MPC appears to have an unknown aetiology.

Thromboxane production by platelets during tumor cell-induced platelet activation.

We have evaluated in a homologous system the mechanisms of platelet activation by cells isolated from fresh human tumor tissues and the role of thromboxane B2 (TxB2) generation in this process. Thirty-eight of the 46 tumor tissues considered showed a high platelet-aggregating activity, with no particular distribution in any specific tumor type. Apyrase caused a nonsignificant reduction in the aggregation response, hirudin did not change it, while iodoacetic acid or p-hydroxymercuriphenylsulfonate, specific cysteine proteinase inhibitors, significantly reduced the platelet-aggregating capacity of these tumor cells. In 9 colon carcinomas and in 8 breast carcinomas the levels of TxB2 produced by platelets after addition of tumor cells were measured: tumor cell-induced platelet aggregation was accompanied by a significant production of the metabolite; indobufen, a cyclooxygenase inhibitor, significantly reduced aggregation and particularly TxB2 production, while the drug had no effect on both parameters if preincubated with tumor cells only. These data suggest that cells isolated from different human tumor tissues activate platelets through the activity of tumor-associated cysteine proteinase(s); platelet aggregation by tumor cells is largely dependent on arachidonic acid metabolism in platelets, while such metabolism in tumor cells does not play a significant role.

Human tumor cells cultured "in vitro" activate platelet function by producing ADP or thrombin.

We studied the effects on platelet function of different human tumour cells cultured "in vitro": Mo T lymphocyte cell line, NCI-N592 small cell lung carcinoma cell line, and 5637 bladder carcinoma cell line. Mo and NCI-N592 cells possessed a slight, dose-dependent platelet aggregating activity, which was completely abolished by apyrase and unaffected by hirudin. The cell-free supernatant also induced an aggregation response, which was very similar to that obtained with tumour cell suspensions. The presence of ADP in the cell-free supernatants of cell suspensions was confirmed by HPLC analysis. On the contrary, aggregation induced by 5637 cells was preceded by a significant lag phase; it was not affected by apyrase but it was abolished by hirudin, and the cell-free supernatant had no effect. These data suggest that Mo and NCI-N592 cells activate platelets by producing ADP, while 5637 cells stimulate platelet function by generating thrombin. The amount of ADP produced by the first two tumour cell lines was measured by bioassay: the extent of such production was similar for both cell lines and the maximum was reached after 60 minutes and maintained for up to 3 hours. These results suggest that neoplastic cells can activate platelets by different mechanisms: such investigations should be performed in homologous systems and in well-defined experimental conditions.

Platelet activation by emotional stress in patients with coronary artery disease.

We studied the effects of experimentally induced emotional stress (mental arithmetic) on different hemodynamic parameters, catecholamine levels, and serum and platelet function tests in 25 postinfarction patients and in 10 apparently healthy, age-matched control subjects. Mental stress (10 minutes) induced significant increments in heart rate, systolic blood pressure, diastolic blood pressure, double product, and cardiac output, indicating a sympatho-adrenal stimulation that was confirmed by a significant increase in serum epinephrine and norepinephrine levels. All of the effects disappeared at minute 10 of recovery. Concomitantly, the test produced a significant increase in platelet aggregation (induced by 3 microM ADP or 1 microgram/ml collagen), the formation of circulating platelet aggregates, and an increase in thromboxane B2 levels in plasma and serum. These effects were also rapidly reversible. Similar activation of hemodynamic parameters and a similar but less evident increase in platelet function by emotional stress were observed in control subjects. A possible artifact due to factitious platelet activation by catheter sampling was excluded with experiments in which a 40-minute rest was introduced after the baseline period and before mental stress; platelet activation did not occur during baseline or rest periods, only after emotional stress. Furthermore, the antiplatelet drug dipyridamole reduced the stress-induced formation of platelet aggregates in postinfarction patients. These results demonstrate the existence of a direct link between emotional stress and platelet function and offer an explanation of one of the mechanisms through which mental stress may be involved in the development of coronary artery disease.