SERPINB3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by inducing a more tolerogenic immune phenotype

Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 \u3bcg/0.1 mL or 15 \u3bcg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria ( 65100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice. Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype

Spin-coated La0.8Sr0.2Ga0.8Mg0.2O3-δ Electrolyte on Infiltrated Anodes for Direct Methane Fuel Cells

Dense micrometric La0.8Sr0.2Ga0.8Mg0.2O3-δ (LSGM) films were deposited by spin-coating on porous LSGM scaffolds characterized by homogeneous pore structure. Porous anodes were infiltrated with aqueous nickel and nickel/copper nitrate solutions, dried and fired at 700°C. Homogeneous metal coating with proper interconnection was observed by SEM, chemical stability was confirmed by XRD, and electrical characterization of anodic substrates was performed. Catalytic activity of different anodes was evaluated ex-situ in a quartz micro-reactor fed with CH4:CO2 mixtureat range 650 and 700°C. To investigate the redox properties of the metallic phases, the anodic substrates were subjected to redox ageing cycles and characterized by H2-TPR

[HDL inhibit cytokine production in a mouse model of urate crystal-induced inflammation].

Objectives: To evaluate whether high density lipoproteins (HDL) affect monosodium urate (MSU) crystal-induced inflammation in the murine air pouch model. Methods: MSU crystals were prepared by Denko's method and sterilized by heating at 180°C for 2 h before each experiment. Human HDL were isolated from peripheral blood of healthy volunteers. MSU crystals (2 mg in 1 ml of PBS) were injected into subcutaneous air pouches in mice in the presence or absence of HDL (0.1 mg). Negative control pouches received 1 ml of PBS. To recover pouch fluid, the pouches were washed with 2 ml of PBS after the animals were sacrificed. The leukocyte count in the lavage fluids was obtained using a hemocytometer and differential leukocyte count was determined by May-Grünwald-Giemsa staining. IL-6, KC, CCL2 and TNF-α levels were measured in exudates by ELISA. Results: MSU crystals increased the number of leukocytes and the neutrophil migration, as well as the concentrations of IL-6, KC and CCL2 in pouch fluids, while the TNF-α levels were not detectable. The treatment with HDL led to a reduction in all inflammatory parameters: the leukocyte count decreased by 73%; the neutrophil density decreased by 35%; the IL-6, KC and CCL2 concentration decreased by 4-, 6- and 5-fold respectively. Conclusions: This study shows that HDL may limit the inflammatory process by inhibiting leukocyte recruitment and cytokine release. HDL are likely to represent a mechanism of control of crystal-induced inflammation

S7A:7 Administration of serpinb3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by an immunomodulatory effect

Background Abnormal apoptosis and clearance of cellular debris concur to development of systemic lupus erythematosus (SLE). SERPINS (serin-protease inhibitors) are ancient molecules regulating immune homeostasis. SERPINB3 modulates apoptosis and is hypoexpressed on SLE B cells. Aim To explore the effects of SERPINB3 administration in murine lupus models, focusing on glomerulonephritis. Methods NZB/W F1 and MRL/lpr mice were used. 40 NZB/W F1 mice were divided into 4 groups of 10 mice each and intraperitoneally injected twice a week starting before occurrence of proteinuria traces (group 1 and 2, prophylactic approach) or after development of proteinuria 30 mg/dl (group 3 and 4, therapeutic approach) with hrSERPINB3 (7.5 µg/0.1 mL prophylactic approach, or 15 µg/0.1 mL therapeutic approach) or PBS (0.1 mL). 20 MRL/lpr mice were injected with hrSERPINB3 (group 5, n=10) or PBS (group 6, n=10) with a prophylactic approach. We assessed time of occurrence and titers of anti-dsDNA and anti-C1q antibodies by ELISA; proteinuria and serum creatinine; overall- and proteinuria-free survival. Six NZB/W F1 mice were sacrificed at week 27, while 10 MRL/lpr mice at week 13 and another 10 at 16/18 weeks for histological kidneys comparison. Flow-cytometry was performed on MRL/lpr splenocytes. Non parametric tests were performed for statistics; proteinuria-free ( Results Levels of autoantibodies were significantly decreased and delayed in group 1 vs group 2, group 3 vs group 4, and group 5 vs group 6 (p Conclusions Administration of SERPINB3 significantly improves disease and delays the onset of severe glomerulonephritis in lupus-prone mice. SERPINB3 may influence immune-cell function through immunoregulatory effects involving promotion of Treg

Guidelines for the diagnosis, prevention and treatment of osteoporosis

The guidelines for the osteoporosis management were first drafted by a working group and then critically evaluated by the board of SIOMMMS. The most relevant points are: Definition: Osteoporosis is defined as a quantitative and qualitative deterioration of bone tissue leading to increased risk of fracture. Postmenopausal and senile osteoporosis are defined as primitive. Diagnosis: The cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T-score values -2.5 is usually not justified. Pharmacological intervention: The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk. This is the case only when the risk of fracture is rather high. FRAX™ is recognized as a useful tool for easily estimate the long-term fracture risk. SIOMMMS with these guidelines is committed to validate and further develop this diagnostic tool

Preparation and characterization of nano cobalt oxide

Cobalt oxide Co(3)O(4) is prepared according to several methods i.e. oxalate decomposition (CoAO), surfactant-assisted precipitation (CoCTAB), sol-gel technique (CoSG) and polymer combustion (CoPVA). The solids are characterized by XRD, FTIR, TPR and TEM analysis. The method via oxalate decomposition (CoAO) appears as that giving the smallest particles nanostructured with an almost monomodal distribution, whereas the CoPVA needs to be calcined at the highest temperature in order to have pure Co(3)O(4). As a consequence on CoPVA the largest particle size is found. The reducibility by H(2) of cobalt oxide particles having the smallest (CoAO) and the largest particle size (CoPVA) is found to depend on the particle dimensions and, where the distribution is monomodal, the reduction steps Co(3)O(4) -> CoO -> Co appear clearly distinct and the temperatures relative to the two reduction steps are well beyond those monitored on microprepared oxide, where only a gross and unique reduction peak is envisaged

Bone organic matrix components: their roles in skeletal physiology

Bone matrix is composed mainly of inorganic materials, while the bone organic compartment is a minor and complex structural entity, surrounding and supporting cells. Three major classes of biomolecules are involved in this organic part: structural proteins, specialized proteins, and proteoglycans. This review will briefly summarize our knowledge about the role and regulation of these specific bone components

Primary hyperparathyroidism in the nineties. How has it changed ?

Primary hyperparathyroidism is the most common cause of hypercalcemia and 80-85% of the patients have parathyroid tumors. The purpose of this retrospective review was to analyse whether differences exist between patients with parathyroid tumors treated in the 1980s and 1990s. Between 1980-1997, 253 patients underwent initial surgical neck exploration for hyperfunctioning parathyroid tumors. Renal (polyuria, nocturia, renal colic due to lithiasis), rheumatologic (bone and joint pain), neurological (fatigue, memory loss, depression) and gastrointestinal (dyspepsia, anorexia, nausea) symptoms were recorded and main biochemical parameters were measured. In all patients one or more preoperative localization procedures were carried out prior to successful parathyroidectomy, and the confirmation of imaging findings was obtained after surgery. The patients were divided in two groups. Group A: 121 patients undergoing surgery from 1980-1989; Group B: 132 patients in whom parathyroidectomy was performed from 1990-1997. There were no differences (p=NS) between the two groups in average age, preoperative serum creatinine and intact-PTH levels. Symptoms were most common in Group A, and pre-operative serum calcium levels were significantly lower in Group B. Ultrasonography (n=191) sensitivity did not improve significantly (82.8% vs 82.9%), but positive predictive value (PPV) was higher (89.8% vs 96.0%). CT-scan (n=73) sensitivity was 79.2% and 82.6%, and PPV was 95.0% and 100% in Groups A and B, respectively. 201Tl/99mTc subtraction scintigraphy (n=111, Group A) was 84.6% sensitive (PPV=92.6%) whereas 99mTc-sestamibi scanning (n=90, Group B) was 85.1% sensitive (PPV=96.1%). In conclusion, the clinical features of parathyroid tumors has changed in the nineties and increasing asymptomatic pHPT rate has been found. Although sensitivity and PPV of preoperative localization procedures has improved moderately, at present noninvasive techniques may offer excellent results and should be used in all patients with suspected parathyroid tumors

Ni and Ni-Co La0.8Sr0.2Ga0.8Mg0.2O3 Infiltrated Cells in H2 and CH4/CO2 mixture

La0.8Sr0.2Ga0.8Mg0.2O3- (LSGM) based fuel cells infiltrated with different metal catalysts were fabricated and tested both in H2 and CH4/CO2 mixture. Ni, Co, Ni-Cu, Ni-Co LSGM impregnated powders were investigated for the dry reforming of methane reaction (DRM) (CH4+CO22CO+2H2). The catalytic activity for CH4 and CO2 conversion followed the order NiNi-Co>Co>Ni-Cu. Both Ni and Ni-Co catalysts, investigated versus time (50 hours) on stream of CH4/CO2=1.5 at 800°C, did not show any sign of deactivation indicating their stability toward coke deposition. Anyway, evidence of few carbon filaments were revealed by SEM micrographs and the carbon amount evaluated by TG-DTA analysis. Ni-LSGM and Ni-Co LSGM cells showed regarding electrochemical performance both in H2 and CH4/CO2 mixture in the 650-750°C temperature range