localization and treatment of tumor-induced osteomalacia

Tumor-induced osteomalacia (TIO) or oncogenic osteomalacia (OOM) is a rare paraneoplastic renal phosphate wasting syndrome. The disease is mostly triggered by small, benign mesenchymal tumors that express somatostatin receptors (SSTR) and produce excessive levels of fibroblast growth factor 23 (FGF 23) or other phosphatonins. These reduce the phosphate back resorption in the proximal tubules of the kidneys, thereby causing hypophosphatemia and lead to an absolute or relatively low calcitriol serum concentration. The main symptoms include muscle weakness, bone pain and recurrent insufficiency fractures secondary to sometimes pronounced osteomalacia. The suspected diagnosis can only be confirmed by determination of the phosphate level.
It can often take years before the tumor is successfully localized. The necessary tumor localization is often the most difficult step in the treatment before the OOM can be curatively treated by open surgical resection of the tumor. In recent years new approaches for faster tumor localization and treatment of the tumor have been developed. Positron emission tomography (PET) in co-registration with computed tomography (68Ga-DOTA-TATE PET/CT) is currently the most sensitive imaging methodology for tumor detection. The application of the monoclonal FGF 23 antibody burosumab represents a promising new option in the treatment of inoperable adult OOM.
Die onkogene Osteomalazie (OOM) oder tumorinduzierte Osteomalazie (TIO) ist ein seltenes paraneoplastisches Phosphatverlustsyndrom.
Ausgelöst wird die OOM meist durch kleine gutartige Somatostatinrezeptor-positive Tumoren, die meist über eine ektope Überproduktion von FGF23 („fibroblast growth-factor 23“) oder anderen Phosphatoninen zu einer verminderten renalen Phosphatrückresorption im proximalen Nierentubulus und folglich einer Hypophosphatämie sowie einer absolut bzw. relativ erniedrigten Calcitriolserumkonzentration führen. Zu den Hauptsymptomen gehören Muskelschwäche, Knochenschmerzen und rezidivierende Insuffizienzfrakturen infolge einer zum Teil ausgeprägten Osteomalazie. Die Verdachtsdiagnose kann nur durch die Bestimmung des Phosphatspiegels gestellt werden.
Bis zur erfolgreichen Tumorlokalisation und Therapieeinleitung vergehen oft Jahre. Hierbei stellt häufig die dazu notwendige Tumorlokalisation den schwierigsten Schritt in joplink Rabbit anti-bovine IgG Antibody der Behandlung dar, bevor die OOM durch eine offen-chirurgische Tumorresektion kurativ behandelt werden kann. Neue Ansätze zur schnelleren Tumorlokalisation und zur Therapie der OOM wurden in den letzten Jahren entwickelt. So ist die Positronenemissionstomographie (PET) in Koregistrierung mit einer Computertomographie (68Ga-DOTA-TATE PET/CT [Gallium-68-Dotatate-Positronenemissionstomographie/Computertomographie]) aktuell das sensitivste Verfahren zur Tumordetektion. Der Einsatz des monoklonalen FGF23-Antikörpers Burosumab stellt eine vielversprechende Therapieoption bei inoperablen Erwachsenen dar.

Context dependent induction of autoimmunity by TNF signaling deficiency

TNF inhibitors are widely used to treat inflammatory diseases; however, 30-50% of treated patients develop new autoantibodies and 0.5-1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high affinity autoantibodies are often made. We found that TNF deficiency in Sle1 mice induced TH17 T cells and enhanced the production of germline encoded, T-dependent IgG anti-cardiolipin antibodies but did not induce GC formation or precipitate clinical disease.
We then asked whether a second hit could restore GC formation or induce pathogenic autoimmunity in TNF deficient mice. By using a range of immune stimuli, we found that somatically mutated autoantibodies and clinical disease can arise in the setting of TNF deficiency via extrafollicular pathways or via atypical GC-like pathways. This breach of tolerance may be due to defects in regulatory signals that modulate the negative selection of pathogenic autoreactive B cells.

Hepatitis-A Infection-Induced Secondary Antiphospholipid Syndrome With Neuro-ophthalmological Manifestations

Antiphospholipid syndrome (APS) is a multisystem autoimmune disorder that can affect children and adults alike, with a similar spectrum of thrombotic events, predominately deep vein thrombosis and stroke. It is characterized by recurrent arterial or venous thrombosis and recurrent fetal loss with the presence of antiphospholipid antibodies (aPL) like antibodies to beta-2-glycoprotein I (B-2-GPI) and anticardiolipin (aCL). The disease could be classified into primary APS in the absence of an underlying disease or secondary APS occurring secondary to autoimmune diseases, infections, malignancies, and sometimes medication use.
In the absence of clinical manifestations of APS, transient non-thrombogenic antiphospholipid antibodies are seen more commonly in children, predominantly after childhood infections.
Cases with clinical manifestations of APS associated with different types of infections have been reported in the literature to keep track of potential triggering causes and take measures to prevent or treat the disease manifestations. This case documents the case of hepatitis-A as a triggering viral infection, causing secondary APS in a child.

Effects of Selected Adjuvants on Immunogenicity and Protectivity of Pasteurella multocida Bacterin Vaccine in Chickens

Avian pasteurellosis (fowl cholera) is an important disease affecting domestic and wild birds all over the world. Although the capsular type A of Pasteurella multocida is mostly involved, other capsular types are occasionally incriminated. The present study aimed at investigating the effect of some adjuvants on immunogenicity and protectivity of P. multocida bacterin in chickens, compared to an Iranian commercial vaccine.
Eight-week-old chicken pullets were double vaccinated with an interval of three weeks. Vaccine immunogenicity testing was conducted using an in-house indirect enzyme-linked immunosorbent assay and assessing serum antibody titers at 7, 14, and 21 days post-primary and 14 days post-secondary immunization. The possible adverse effects were recorded by a poultry-disease expert.
For evaluating the vaccine protection rate, chickens were subjected to 2×Lethal Dose 50%of a virulent P. multocida strain two weeks post-secondary immunization. The rate of live and normal animals was regarded as protection rate 7days after the exposure. The findings showed that oil adjuvants Montanide ISA 70-and Montanide ISA 71-containingvaccines (with or without saponin) caused a powerful immune reaction than the aluminum adjuvanted vaccine and commercial vaccine (P<0.05).
Significant protection against challenge was merely induced by the oil adjuvanted vaccines (P<0.05). The majority of the studied chickens showed inflammation at the injection site (yellow) throughout the trial. Vaccines made by Montanide ISA 70 and Montanide ISA 71 are novel and effective inactivated vaccines that are able to cause significant protection to fowl cholera disease.

A sandwich-type electrochemical immunosensor using trimetallic nanozyme as signal amplification for NT-proBNP sensitive detection

Heart failure (HF) is a major public health problem trigged by a heart circulation disorder. Early detection and diagnosis are conducive to the prevention and treatment of HF. N-terminal B-type natriuretic peptide precursor (NT-proBNP) is considered to be a sensitive diagnostic biomarker of HF. In this study, we constructed a NT-proBNP sandwich electrochemical immunosensor by using electroplated gold nanoparticles (Au NPs) as the substrate and utilizing rough-surfaced trimetallic Au@PdPt nanozymes (Au@PdPt RTNs) as current signal amplification.

The Au NPs as substrate material modified glassy carbon electrode (GCE) have excellent conductivity and biocompatibility, which not only accelerate electron transfer rate, but also improve the loading capacity of primary antibody (Ab1). Moreover, the Au@PdPt RTNs were synthesized by a one-pot method and used as the labels to bound with secondary antibodies (Ab2) via the Pt-N. The large specific surface area and excellent catalytic properties for H2O2 of Au@PdPt RTNs can effectively enhance the stability and sensitivity of the immunosensor. With the favorable cooperation of Au NPs and Au@PdPt RTNs, the constructed immunosensor exhibited a wide concentration range from 0.1 pg mL-1 to 100 ng mL-1 and a low detection limit of 0.046 pg mL-1. Furthermore, the accuracy of the analysis of NT-proBNP in diluted human serum samples was satisfactory. The results revealed the electrochemical immunosensor has a prospective application in clinical detection.

Rabbit Polyclonal antibody Anti-CRBN

50 µg 349 EUR

Rabbit anti Bovine

0.1mg 343 EUR

Rabbit anti Bovine IgG

2 mg 281 EUR

Rabbit anti Bovine IgG

5 mg 347 EUR

Rabbit anti Bovine IgA

1 mg 216 EUR

Rabbit Anti-Bovine IgA, unlabeled

0.5 mg 202 EUR

Rabbit Anti-Bovine IgM, unlabeled

0.5 mg 202 EUR

Rabbit Anti-Bovine Casein IgG

100 ug 445 EUR

Rabbit Anti-bovine Catalase antiserum

100 ul 432 EUR

Rabbit Anti-Bovine tubulin antiserum

100 ul 457 EUR