Ultrasonographic Modification of Liver Steatosis and Visceral Fat Induced by Treatment With Losartan and Simvastatin in Hypertensive Normocholesterolemic Obese Patients

Angiotensin II has been proposed as a lipid metabolism regulator. It is known that adipocytes secrete a variety of protein, such as TNFα, plasminogen activator inhibitor (PAI)-1, leptin, resistin and adiponectin; these proteins have a wide range of biological effects and are associated with insulin resistance. Adipocytes also produce angiotensinogen and angiotensin II and a local renin-angiotensin system (RAS) is present in adipose tissue. In overweight or obese hypertensive normocholesterolemic patients the treatment with AT1-receptor blocker (Losartan) may have a better effect on hepatic steatosis and visceral fat deposition than the antihypertensive treatment with calcium channel blocker (amlodipine). Simvastatin will be added to both groups. The aim of this study is to evaluate the effect of losartan and simvastatin on ultrasonographic qualitative and quantitative parameters in overweight or obese hypertensive normocholesterolemic patients with hepatic steatosis.

Start Date01 Apr 2008

Sponsor / Collaborator

Universitiamo By Unipv

100 Clinical Results associated with Losartan/Simvastatin

100 Translational Medicine associated with Losartan/Simvastatin

100 Patents (Medical) associated with Losartan/Simvastatin

Literatures (Medical) associated with Losartan/Simvastatin

01 Nov 2022·Nuclear Medicine and Biology

Evaluation and selection of a lead diabody for interferon-γ PET imaging

Article

Author: Rezazadeh, Farzaneh ; Viola, Nerissa T ; Peraino, Nicholas ; Ramos, Nicholas ; Schomburg, Fritz ; Barr, Stephen ; Saliganan, Allen-Dexter ; Rancour, David

INTRODUCTIONInterferon-γ (IFN-γ) is an appealing target to evaluate immune response in cancer immunotherapy as it is a hallmark of an active immune system. Imaging and detection via immunopositron emission tomography (immunoPET) of this soluble cytokine has been made feasible using a ⁸⁹Zr-labeled (t _1/2 ~ 3.27 d) monoclonal antibody (mAb). Because of its size, using a full-length mAb as an imaging vector is not ideal for repeat serial imaging because of its prolonged blood pool residency and tumor accumulation resulting in lengthier wait times between administration and imaging. This consequently impacts the potential to image a dynamic immune response in real time. This work compares ⁸⁹Zr-labeled diabodies (Db) designed with variable linker lengths between the V_H and V_L regions with the goal of selecting a lead Db for future studies.METHODS AND RESULTSFour Db fragments with various linker lengths (HL-n, n = 7-13 amino acids) were each conjugated to desferrioxamine (DFO). The number of attached chelates was analyzed via mass spectrometry with all immunoconjugates exhibiting one unit of DFO attached. Db-DFO conjugates were subsequently radiolabeled with zirconium-89. All constructs radiolabeled with high yields. Each radioimmunoconjugate was tested for reactivity to IFN-γ. All tracers except for [⁸⁹Zr]Zr-DFO-NCS-anti-IFN-γ HL-9 exhibited comparable immunoreactivities (>90 %) to the radiolabeled parent mAb (95.8 %). At 24 h post-labeling, the IRF values were retained except for the HL-13 construct. Imaging scans and tissue distribution studies acquired in mice bearing CT26 syngeneic colorectal tumors between 1 and 24 h post-tracer administration demonstrated variable clearance kinetics and tumor localization of each radiotracer. HL-7 had higher binding in non-tumor tissues compared to HL-11 and HL-13 at 3 h p.i. Competitive binding studies versus unmodified parent mAb (AN-18) demonstrated blocking of radiolabeled HL-11 and HL-13. [⁸⁹Zr]Zr-DFO-NCS-anti-IFN-γ HL-7 was inadequately blocked.CONCLUSIONDespite nuanced differences in linker lengths, our data demonstrates that [⁸⁹Zr]Zr-DFO-NCS-anti-IFN-γ HL-11 exhibited the best radiotracer properties for the assessment of IFN-γ production in vivo. Work is currently underway to test the potential of using shorter-lived isotopes, like copper-64 (t_1/2 ~ 12.7 h) to match pharmacokinetics and half-lives.

26 Jun 1979·BiochemistryQ3 · BIOLOGY

5S RNA-protein complex from an extreme halophile, Halobacterium cutirubrum. Comparative studies on reconstituted complexes

Q3 · BIOLOGY

Article

Author: Matheson, Alastair T. ; Willick, Gordon E. ; Nazar, Ross N.

Partially and fully reconstituted complexes of the 5 S RNA and two 5 s RNA binding proteins (HL13 and HL19) from H. cutirubrum were examined using ethidium bromide binding, CD spectra, and limited nuclease digestion.The binding of 5 S RNA to HL13 was studied by means of the quenching of tryptophan fluorescence; a value of 10⁸M^-1 was estimated for the association constant in 3.7M KCl.A study of the CD spectra in the 200 to 240-nm region also indicated that this protein underwent some conformational change when bound.The addition of HL13 chased ethidium bromide bound to the 5 S RNA.The only effect observed on binding HL19 was an enhanced association constant for HL13 as inferred from a change in shape of the ethidium bromide chasing curve.Addition of HL13 also gave rise to a partial protection of the 5 S RNA against T₁ RNase digestion; in contrast, it brought about an enhanced susceptibility to pancreatic RNase digestion.Addition of HL19 had no effect in either case.Thus, protein HL13 alone is responsible for the corresponding CD and nuclease digestion observations on the native H. cutirubrum 5 S RNA-protein complex and 5 S RNA previously reported.Furthermore, despite the limited sequence homol., there is a marked structural homol., within their resp. 5 S RNA complexes, between protein HL13 from H. cutirubrum and protein EL18 from Escherichia coli.Similarly, HL19 appears to have a similar role as EL5 in the E. coli complex.

MetallomicsQ2 · BIOLOGY

3-Hydroxy-4-pyridinone derivatives as metal ion and amyloid binding agents

Q2 · BIOLOGY

Article

Author: Chris Orvig ; Gwendolyn A. Bailey ; Jacqueline F. Cawthray ; Mariona Sodupe ; Maria A. Telpoukhovskaia ; Brent D. G. Page ; Brian O. Patrick ; Jorge Alí-Torres ; Lauren E. Scott ; Cristina Rodríguez-Rodríguez

Metal ions have been implicated in several neurodegenerative diseases, including Alzheimer's disease, as their dyshomeostasis may lead to production of reactive oxygen species as well as increased toxicity of amyloid protein aggregates. In this work, we present design and synthesis of three novel multifunctional hydroxypyridinone ligands, HL11, HL12, and HL13, bearing benzothiazole and benzoxazole functionalities. We study the ability of these compounds to bind metal ions Cu(II), Zn(II), and Fe(III), as well as their antioxidant activity and cytotoxicity. Additionally, we determine the pro-ligands' (compounds prior to chelation) propensity to target amyloid protein. Through these studies we determine the effect of combining amyloid- and metal-binding functionalities within the HPO scaffold on different aspects of AD pathology.

100 Deals associated with Losartan/Simvastatin

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipidemias	Phase 1	-	HANALL BIOPHARMA Co., Ltd.	-
Hypertension	Phase 1	-	HANALL BIOPHARMA Co., Ltd.	-

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