Specific cytokine-adsorbing columns have also been developed with significant removal rates of proinflammatory cytokines in animal and human sepsis [63] reflecting benefits of modulation of the cytokine profile. Sepsis is, PD-0332991 purchase however, a complex disease entity where removal of single cytokines has marginal effect on the clinical course, as reflected by the many unsuccessful studies using neutralizing antibodies to specific cytokines. The pattern and degree of the inflammatory response, however, is quite different in LDL apheresis as compared to sepsis. Generally, LDL apheresis columns seem to adsorb many proinflammatory cytokines and to some degree

seem to increase some of the anti-inflammatory cytokines, although there are differences between different LDL apheresis columns and studies vary regarding types of patients included. Furthermore, no studies have addressed how or if changes in pro- and anti-inflammatory cytokine profile in LDL apheresis relate to changes in clinical endpoints. Some data indicate that CRP could play a causative role in the pathogenesis of atherosclerosis [64, 65], but data are conflicting

and a consensus has yet to be established [66, 67]. The JUPITER trial clearly PD0325901 ic50 demonstrated that clinical endpoints were reduced along with reductions in CRP and LDL cholesterol in healthy persons with LDL cholesterol below 3.4 mm and CRP below 2 mg/l before intervention [68]. Puntoni Resveratrol et al. [69] found higher levels of CRP in heFH patients compared with controls, however not significantly so. Kojima et al.

[55] found a significant decrease in CRP when treating hypercholesterolemic patients with LDL apheresis. The findings were reproduced by Kobayashi et al. [58, 59] who treated patients with PAD with LDL apheresis. Herchovici et al. [70] found a significant decrease in CRP during LDL apheresis in hypercholesterolemic patients, with differences observed between the different LDL apheresis systems. Our group also noted a significant decrease in CRP during LDL apheresis in heFH [46]. Thus, it seems that most LDL apheresis treatments reduce the inflammatory marker CRP, a factor that could be of pathogenetic importance in subjects prone to atherosclerosis. Lowering of CRP is associated with lowering of clinical end points [68], but it remains to be proven if reduction of CRP in LDL apheresis relates to reduction in endpoints. Fibrinogen, the precursor of fibrin, is associated with risk for cardiovascular disease [71]. Wang et al. [57] found a significant decrease in fibrinogen during LDL apheresis in patients with CAD, a finding that was confirmed by Kobayashi et al. [59] performing LDL apheresis on patients with peripheral artery disease. Otto et al. [56] found a decrease in fibrinogen levels for two types of LDL apheresis in whole blood. Our group compared three different LDL apheresis techniques and found significant decreases in fibrinogen for all columns [72].

First, we examined whether FITC-FSL-1 is able to activate macrophages, because there is a possibility that FITC conjugation affects the ability of FSL-1 to activate them.13 It was found that both FITC-FSL-1 and FSL-1 induced tumour necrosis factor-α production by a murine macrophage cell line, RAW264.7 cells, in a dose-dependent manner (Fig. 1), suggesting that FITC-FSL-1 is also able to activate macrophages, possibly through TLR2. However, it remains unknown

how FSL-1 is processed in macrophages after recognition by TLR2. To address this question, an experiment was carried out to determine whether FSL-1 is internalized by macrophages after recognition by TLR2. RAW264.7 cells were incubated with FITC-FSL-1 for 2 hr at 4° (on ice) or at 37°, and then uptake of FSL-1 was determined. FSL-1 was found in the cell membrane but not in the cytosol of RAW264.7 selleck chemicals llc cells at 4° (Fig. 2a,c). However, FSL-1 was found in both the cell membrane Selumetinib cell line and the

cytosol of the cells at 37° (Fig. 2b,d). These results suggest that FSL-1 is clearly internalized into the cells in a temperature-dependent manner. To confirm whether FSL-1 is specifically internalized, effects of unlabelled FSL-1 on FITC-FSL-1 uptake were also examined. It was found that unlabelled FSL-1 significantly inhibited FITC-FSL-1 in a dose-dependent manner (Fig. 3), suggesting that FITC-FSL-1 uptake by Endocrinology antagonist the cells occurs specifically. It has been demonstrated that modes of endocytosis of small soluble

molecules can be mainly divided into three pathways: clathrin-, caveolae- and lipid raft-dependent endocytic pathways.17 Therefore, experiments were carried out to determine the effects of three chemicals, Nys, CPZ and MbCD, on internalization of FSL-1. Nys selectively disrupts caveolae- and lipid raft-dependent endocytosis but has no effect on clathrin-dependent endocytosis.18 CPZ disrupts clathrin-dependent endocytosis.19 MbCD disrupts both lipid raft- and clathrin-dependent endocytosis.20–23 It has been demonstrated that TLR2 is enriched in lipid rafts24 and that the TLR2 ligand LTA is internalized into cells with TLR2 via lipid rafts.15 The present study demonstrated that Nys had no effect on FSL-1 uptake by RAW264.7 cells (Fig. 4a–c), suggesting that FSL-1 is not internalized by caveolae- and lipid raft-dependent endocytosis. Both CPZ and MbCD inhibited FSL-1 uptake by the cells in a dose-dependent manner (Fig. 4d–i), suggesting that FSL-1 is internalized into macrophages by a clathrin-dependent endocytosis. The next experiment was therefore carried out to determine whether FSL-1 is co-localized with clathrin in cells. RAW264.7 cells were incubated for 2 hr with FITC-FSL-1, permeabilized with Cytofix/Cytoperm (BD Biosciences), and treated with an anti-clathrin mAb.

In line with this, labial biopsies and acinar cell primary cultures from SS patients show an aberrant expression and activation of inflammatory LY294002 mediators in epithelial cells together with defective activity and localization of key enzymes and channels involved in saliva secretion [5–8]. This observation supports the hypothesis that acinar cells are involved actively in the pathogenesis of SS and provides new evidence to the search of early biomarkers for diagnosis and/or disease activity. At the prediabetic stage, the non-obese diabetic (NOD) mouse model of Sjögren’s syndrome has the

unique characteristic of developing a deep secretory dysfunction with mild infiltration of the glands [9–11] consistent with a structural–dysfunctional aetiology. In keeping with this, early neurotransmitter receptor-signalling alterations have been reported in NOD females’ submandibular glands unrelated to the onset of the autoimmune response [12–14]. Among them, a progressive loss of activity of the neural isoform of nitric oxide synthase (NOS 1) in NOD exocrine glands at the Sjögren’s syndrome-like period has been described

[12,15]. The lower levels of NOS activity were found in glands of 16-week-old NOD mice that presented increased apoptosis of acinar cells and increased levels of tumour necrosis factor (TNF)-α, among other T helper type 1 (Th1) cytokines in the serum [15,16]. Vasoactive intestinal peptide (VIP), described initially as a vasodilator and prosecretory neuropeptide, has trophic effects on acini [17,18] and strong anti-inflammatory properties in Cobimetinib several models of chronic inflammatory diseases [19–21]. Prediabetic NOD mice treated systemically with VIP showed increased serum interleukin (IL)-10 and reduced Th1 cytokine levels very [22] while gene-transfer of VIP onto NOD submandibular

glands prevented saliva secretion loss and partly reduced glandular Th1 cytokine expression [23]. Furthermore, VIP showed a clear anti-apoptotic effect on acinar cells isolated from NOD submandibular glands driven to apoptosis through TNF-α/TNF-αR1-mediated pathways [16]. An adequate balance of apoptosis of epithelial cells and their silent clearance by professional phagocytes is central for gland homeostasis. On this basis, we hypothesized that the local expression of VIP/VPAC system could modulate acinar cell apoptosis and clearance, thus influencing gland homeostasis. We present evidence on a progressive decline of VIP expression in submandibular glands of NOD mice that encompasses a loss of acinar cells through apoptotic mechanisms. We also show that apoptotic acinar cells are removed by NOD macrophages with a reduced phagocytic efficacy compared to control macrophages, although in a suppressor manner that is stabilized by VIP.

The PCR-sequencing of 30 A. flavus isolates detected from clinical and environmental samples confirmed the mycological

learn more identification. Our findings underline the importance of environmental surveillance and strict application of preventive measures. “
“Cysteine dioxygenase (CDO) is involved in regulation of intracellular cysteine levels by catabolising the cysteine to sulphite and sulphate. In keratinolytic fungi, sulphite is actively excreted to reduce disulphide bridges in keratin before its enzymatic degradation. The pathogenicity role of CDO was confirmed in cysteine-hypersensitive and growth-defective ΔCdo mutant of Arthroderma benhamiae on hair and nails. We analysed the CDO expression regulation in T. mentagrophytes (anamorph of A. benhamiae) mycelia by determining

the Cdo mRNA and CDO protein levels and by analysing the proportion of two molecular forms of CDO in response to l-cystine exposure. Cdo mRNA levels in mycelia lysates were detected by reverse-transcription real-time polymerase chain reaction and CDO protein by western blot using mouse CDO-specific hyperimmune serum. The Cdo mRNA level increased gradually 2.5–4.5 h after exposure of the mycelium to l-cystine. The CDO protein, detected as two bands of different mobility, appeared earlier in comparison to mRNA (1 h) and culminated after 24 h. More mobile form prevailed after 4.5 h. The comparison of the dynamics in the RXDX-106 in vivo Cdo mRNA and CDO protein levels indicates that T. mentagrophytes responds to l-cystine by increased transcription and apparently decreased degradation of the CDO and by changing towards higher mobility molecular form, similar to previous reports describing mammalian analogue. those “
“Cysteine dioxygenase (CDO, EC 1.13.11.20) catalyses the oxygenation of cysteine to cysteine sulphinic acid leading to the production

of sulphite, sulphate and taurine as the final metabolites of cysteine catabolism. Keratinolytic fungi secrete sulphite and sulphate to reduce disulphide bridges in host tissue keratin proteins as the first step of keratinolysis. In the present study, we describe the identification of cDNA, as well as expression and characterisation of recombinant CDO protein from Trichophyton mentagrophytes. The cDNA was amplified using primers designed on the basis of high conservancy CDO regions identified in other fungi. PCR product was cloned and sequenced. Recombinant CDO was expressed in Escherichia coli, and affinity purified and identified by matrix-assisted laser desorption/ionization – time-of-flight mass spectrometry (MALDI-TOF MS). Enzyme activity was assayed by monitoring the production of cysteine sulphinate using mass spectrometry. The Cdo cDNA encodes for a protein consisting of 219 amino acids. Recombinant CDO protein C-terminally fused with a His tag was purified by affinity chromatography. The CDO purified under native condition was proved to be enzymatically active. Protein identity was confirmed by MALDI-TOF MS.

This possibility seemed to be strengthened by the observation

that SIGNR1 physically associates with Dectin-1 constitutively in cells over-expressing SIGNR1 and Dectin-1 (data not shown). Moreover, SIGNR1 and Dectin-1 co-localized to part of the phagosomal membrane in RAW-SIGNR1/Dectin-1 cells (data not shown). This is not the case in rpMϕ, where association/co-localization of SIGNR1 and Dectin-1 was not observed without stimulation, as reported in the case of TNF-α production by collaboration between TLR2 and Dectin-1 8. However, Dectin-1 was recruited to the phagosomal membrane where SIGNR1 captures microbes, and both molecules were detected to physically associate with each other in a time-dependent manner after stimulation. The oxidative burst of RAW-SIGNR1 cells in response to live C. albicans was too weak Selleckchem MAPK inhibitor to detect (data not shown). This may be due to the fact that the cell wall in the live microorganism is covered with mannoproteins, preventing Dectin-1 from accessing the β-glucan ligand. However, RAW-SIGNR1 cells showed significant candidacidal

activity, and this activity was substantially dependent Seliciclib order on Syk-mediated signaling. When RAW-SIGNR1/Dectin-1 cells (data not shown) and rpMϕ were exposed to live microbes, β-glucan appeared to be accessible to Dectin-1, and SIGNR1 and Dectin-1 co-localized to part of the phagosomal membrane. Therefore, it is feasible that such cellular events effectively induce candidacidal activity. Tangeritin It is not clear how SIGNR1 utilizes Syk-mediated signaling though Dectin-1. It has been reported that cross-linking of SIGNR1 by neo-glycoprotein containing mannose residues and specific antibody induces the activation of JNK and NF-κB, leading to the production of TNF-α 31, IL-12 32 and IL-10 33. Therefore, it is plausible that SIGNR1

transduces the signal by itself. However, RAW264.7 cells expressing the SIGNR1 truncated cytosolic portion were still able to facilitate the oxidative response, suggesting that it is unlikely that there is any direct involvement of the cytosolic portion of SIGNR1 in signal transduction. SIGNR1 in RAW264.7 transfectants is reported to co-localize in lipid rafts with several Src family kinases 31. Therefore, cross-linking of SIGNR1 by ligand/microbes possibly induces activation of the kinases. Alternatively, SIGNR1 might also cooperate with other unidentified molecules than Dectin-1 to induce the Syk-dependent signaling. These possibilities remain to be elucidated in future experiments. In the systemic infection or stimulation, SIGNR1 may not be a major player in the host defense, since SIGNR1 is expressed in limited populations of DCs and Mϕ.

Fibrinolysis is an important defence mechanism against thrombosis, but has only been studied locally in BP and no systemic data are available. The aim of this observational study was to evaluate systemic fibrinolysis and coagulation activation in patients with BP. We measured parameters of fibrinolysis and coagulation by immunoenzymatic methods in plasma from 20 patients with BP in an active phase and during remission after

corticosteroid treatment. The controls were 20 age- and sex-matched healthy subjects. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1) antigen, PAI-1 activity and tissue plasminogen activator (t-PA) antigen were significantly higher in the BP patients with active disease than in healthy controls (P = 0·0001 for all), as were the plasma levels of the fibrin fragment d-dimer and prothrombin fragment

F1+2 (P = 0·0001 for both). During remission after treatment, levels of PAI-1 www.selleckchem.com/products/sorafenib.html antigen and PAI-1 activity decreased significantly (P = 0·008 and P = 0·006, respectively), and there was also a significant decrease in plasma levels of d-dimer (P = 0·0001) and F1+2 (P = 0·0001). Fibrinolysis is inhibited in patients with active BP, due mainly to an increase in plasma levels of PAI-1. Corticosteroids not only induce the regression of BP lesions, but also reduce the inhibition of fibrinolysis, which may contribute PLX-4720 ic50 to decreasing thrombotic risk. Bullous pemphigoid (BP) is an autoimmune blistering disease that occurs typically in the elderly [1] and is burdened with a high risk of death, due mainly to sepsis and cardiovascular events [2]. It involves the skin and rarely the mucous membranes, and is characterized by the presence of blisters usually surrounded by erythematous–oedematous lesions. The diagnosis is supported by histology showing

a subepidermal blister with a dermal mixed inflammatory cell infiltrate usually rich in eosinophils, and a direct immunofluorescence examination of perilesional skin revealing the linear deposition of immunoglobulin (Ig)G and/or C3 in the basement membrane zone (BMZ). Circulating RVX-208 anti-BMZ autoantibodies can be detected by means of an enzyme-linked immunosorbent assay (ELISA) for two hemidesmosomal antigens, BP180 and BP230 [3, 4]. Autoantibodies against these antigens play an important role in the pathogenesis of BP, as well as complement activation and leucocyte infiltration [1, 5]. Inflammatory cells (particularly autoreactive T cells and eosinophils) participate in blister formation by producing and releasing a number of cytokines and soluble factors that amplify and maintain tissue damage [6-8]. The inflammatory response induces an activation of blood coagulation which is involved both locally, by amplifying the inflammatory network in lesional skin, and systemically, by leading to a prothrombotic state [4, 9-12].

The individual PD20FEV1 × 10 was then used for the

subsequent Segmental Allergen Provocation (SAP). Inhaled and segmental allergen challenges were separated by at least 4 weeks. Bronchoscopy was performed as previously described [29, 42]. A volume of 2.5 ml of 0.9% saline was instilled into the anterior basal segment of the left lower lobe (B8 left) and one of the segments of the lingula (B4 or B5 left). Allergen diluted in 2.5 ml of saline was instilled into the anterior basal segment of the right lower lobe (B8 right) and the medial or lateral segment of the right middle lobe (B4 or B5 right). After 10 min, Buparlisib cell line bronchoalveolar lavage was performed in the anterior basal segments of the right and left lower lobes. Patients were re-bronchoscoped FDA approved Drug Library order at different time points: In the first group, the second lavage was performed after 18 h in segments B4 or B5 right and left. Some of these patients also participated in the second part of the trial. This second group was lavaged 10 min and 42 h after segmental allergen challenge (Table 1). In the third arm of the trial, four patients were

lavaged 10 min and 162 h after allergen challenge. In patients who participated repeatedly the segmental allergen challenges were separated by at least six months. In all patients, peripheral blood was taken before bronchoscopy. From seven healthy subjects and seven patients with allergic asthma, 250-ml whole blood was drawn and mixed well with heparin. Cell subtypes were separated by Ficoll centrifugation. PBMC-CD14+ were harvested, and after washing and counting monocytes were separated via immunomagnetic very separation by AutoMACS system (Miltenyi Biotec GmbH, Germany) after labelling with CD14 antibody (Miltenyi Biotec GmbH). CD14+

monocytes were washed; purification was controlled by flow-cytometry (94–98% purified monocytes, contamination with lymphocytes was <2%), and 5 × 105 cells per well were cultured in 1 ml RPMI 1640 medium (GIBCO, Paisley, Scotland, UK) + 10% FCS (Seromed, Berlin, Germany) + 1% penicillin/streptomycin (Biochrom AG, Berlin, Germany) at 37 °C and 5% CO2. Cells differentiated to macrophages in about 5 days. Medium was exchanged every 2 days. The above-mentioned PBMC-CD14+ cells (5 × 105 cells in 1 ml) were stimulated with either human IL-17 (50 ng/ml), LPS (10 ng/ml), leukotriene D4 (LTD4) (10−11 M) or a combination of LPS and LTD4 for a duration of 6, 12 and 24 h. Cells were also stimulated with LTD4 in the presence of the leukotriene antagonist Montelukast. LTD4 was added to cell cultures 30 min after stimulation with Montelukast (10−11 M), and cultures were incubated for 6, 12 and 24 h. Cell culture supernatants were stored at −20 °C until sCD14 measurement with an ELISA kit (IBL Hamburg, Germany) according to the manufacturer’s instructions. Data were analysed by SPSS software package. Results are reported as median (range) or as single values and median (Figs. 2–5).

Hayashino et al.17 in the Japan DOPP study analysed data from 1569 patients with diabetes and 3342 patients without diabetes on haemodialysis. Patients without diabetes had a smaller body mass index and more years find more since the initiation of haemodialysis than those with diabetes, as well as less cardiovascular comorbid conditions. A Cox proportional hazards model was used to investigate the association between presence or absence of diabetes, glycaemic control (HbA1C quintiles) and mortality

risk. Among patients on haemodialysis, patients with diabetes had a higher mortality risk than those without (HR 1.37, 95% CI: 1.08–1.74). The multivariate-adjusted HR for mortality was not increased in the bottom to fourth quintiles of HbA1C (HbA1C 5.0–5.5% to 6.2–7.2%), but was significantly increased to 2.36 (95% CI: 1.02–5.47) in the fifth quintile (HbA1C

≥7.3%). This effect did not appear to be influenced by baseline comorbidity status. The largest study to date is the one by Kalantar-Zadeh et al.18 This study analysed the data of 82 933 maintenance haemodialysis patients in the DaVita outpatient clinics in the USA over a 3-year period. HbA1C values were divided into seven categories, i.e. <5%, ≥10% and 1% increments in between. Unadjusted survival analyses showed paradoxically lower death hazard selleck chemicals llc ratios with higher HbA1C values. When the model was adjusted however, for potential confounders such as demographics, comorbidities, anaemia, dialysis vintage and dose, higher HbA1C values were incrementally associated

with higher death risks.17 The adjusted all-cause mortality and cardiovascular HRs compared with HbA1C in the 5–6% range were 1.41 (95% CI: 1.25–1.60) for HbA1C values ≥10% and 1.73 (95% CI: 1.44–2.08) (P < 0.001). All of these studies have limitations and whether glycaemic control affects survival in diabetic ESKD patients remains unclear. More prospective controlled studies are needed to verify the true relationships between different methods of diabetes management and outcome in dialysis patients. UK Renal Association: Guideline 3.5 – CKD: Preparation for dialysis Nephrology Units should provide or facilitate the optimal management of patients with established renal failure who opt for non-dialytic buy Metformin treatment. Kidney Disease Outcomes Quality Initiative: Guideline 1. Initiation of Dialysis CPG for Hemodialysis Adequacy 1.3 Timing of therapy: ‘When patients reach stage 5 CKD (estimated GFR <15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy. Particular clinical considerations and certain characteristic complications of kidney failure may prompt initiation of therapy before stage 5. (B) Canadian Society of Nephrology: No recommendation. European Best Practice Guidelines: No recommendation. International Guidelines: No recommendation.

This case had typical features of an

adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition. “
“M. Nakamura, H. Ito, Y. Nakamura, R. Wate, S. Kaneko, S. Nakano, S. Matsumoto and H. Kusaka (2011) Neuropathology and Applied Neurobiology37, 307–314 Smad ubiquitination regulatory factor-2 in progressive supranuclear palsy Aims: Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ligase that belongs to the HECT domain ubiquitin ligase family. Smurf2 can interact Pexidartinib cell line with Smad

proteins and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signalling mediators. Phosphorylated Smad2/3 (pSmad2/3) was recently identified in phosphorylated tau (phospho-tau) inclusions in patients with progressive supranuclear palsy (PSP). As Smurf2 is the E3 ligase of pSmad2, we aimed at investigating the relationship Alisertib research buy among Smurf2, pSmad2/3 and phospho-tau in this study. Methods: The brains of six PSP and three control patients without neurological disorder were investigated by immunohistochemical analysis. Results: In the control subjects, Smurf2 immunoreactivity was not demonstrable in the neurones and glial cells, and that for pSmad2/3 was observed exclusively in neuronal and check details glial nuclei. In PSP patients, the pathognomonic neuronal and glial

phospho-tau inclusions were immunopositive for both Smurf2 and pSmad2/3. The intensity of pSmad2/3 immunosignals of neuronal and glial nuclei containing phospho-tau inclusions was less than that for the cells without the inclusions. Triple immunofluorescence staining for Smurf2, pSmad2/3 and phospho-tau revealed co-localization of these proteins within the neuronal and glial inclusions; and in some globose neurofibrillary tangles, the Smurf2 immunoreactivity appeared more centrally distributed than that of pSmad2/3 and phospho-tau. Conclusions: This is the first demonstration of the presence of Smurf2 immunoreactivity in the phospho-tau inclusions in PSP. These findings suggest that Smurf2 plays a significant role in the pathomechanism of PSP by causing abnormal redistribution of neuronal nuclear pSmad2/3 to the cytoplasm. “
“von Economo neurones (VEN) are bipolar neurones located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI), areas affected early in behavioural variant frontotemporal dementia (bvFTD), in which VEN may constitute a selectively vulnerable cellular population. A previous study has shown a selective loss of VEN in FTD above other neurones in the ACC of FTD.

Given the enormous morbidity and mortality associated with these devastating diseases, the potential impact of vitamin D supplementation at a population level is staggering and is certainly worthy of further investigation in well-designed clinical trials. G. D and G. E. conceived the idea of the review. G. D., S. K., J. K., S. R., and G. E. drafted the manuscript and critically reviewed the content. G. D. is supported by the AANF/CMSC

John F. Kurtzke Clinician-Scientist Award, a Goodger Scholarship (University of Oxford), and the NIHR Biomedical Research Centre, Oxford. None. “
“Tauopathies are clinically, morphologically, and biochemically PD0325901 mouse heterogeneous neurodegenerative diseases characterised by the deposition of abnormal tau protein in the brain. The neuropathological phenotypes are distinguished based on the involvement of different anatomical areas, cell types and presence of distinct isoforms of tau in the pathological deposits. The nomenclature of primary tauopathies overlaps with the modern classification of frontotemporal lobar degeneration. Neuropathological phenotypes comprise Pick`s disease, progressive supranuclear palsy,

corticobasal degeneration, argyrophilic grain disease, primary age-related tauopathy (PART), formerly called Navitoclax solubility dmso also as neurofibrillary tangle-only dementia, and a recently characterised entity called globular glial tauopathy. Mutations in the gene encoding the microtubule associated protein tau (MAPT) are associated with frontotemporal dementia and parkinsonism linked to chromosome 17. In addition, further neurodegenerative conditions with diverse aetiologies may be associated with tau pathologies. Thus the spectrum of tau pathologies and tauopathy entities expands beyond the traditionally discussed disease-forms. Detailed FAD multidisciplinary studies are still required understand their significance. “
“Since cystatin C (CysC) in involved in some forms of neurodegeneration, we investigated

the possible relationship between CysC and multiple system atrophy (MSA), including its parkinsonian (MSAp) and cerebellar (MSAc) phenotypes. Cystatin C gene (CST3) haplotypes were determined by PCR followed by KspI digestion in 50 MSA patients and 108 controls. CST3 and cathepsins B, D and L1 mRNA levels were studied in frozen post-mortem caudate nucleus and cerebellar samples of 8 MSAp, 4 MSAc and 18 control brains and analyzed by the deltadeltaCt method. CysC immunohistochemistry was performed on 3 MSAp, 3 MSAc and 3 control cerebella. Additionally, determination of CST3 and cathepsins B, D and L1 mRNA levels and immunohistochemistry for CysC were carried out in cerebella from 3 patients with paraneoplastic cerebellar degeneration, 3 with spinocerebellar ataxia (type 3, SCA3) and 3 with cerebellar ischemia (CI). In the set of blood samples, the CST3 B-haplotype was associated with MSAp (OR 4.86, CI 1.84-13.3).