scholarly journals Long-term therapeutic effect of vitamin D analog doxercalciferol on diabetic nephropathy: strong synergism with AT1 receptor antagonist

2009 ◽  
Vol 297 (3) ◽  
pp. F791-F801 ◽  
Author(s):  
Yan Zhang ◽  
Dilip K. Deb ◽  
Juan Kong ◽  
Gang Ning ◽  
Yurong Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Combination Therapy ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Filtration Barrier ◽  
Vitamin D Analog ◽  
Long Term Treatment

The intrarenal renin-angiotensin system (RAS) plays a key role in the development of diabetic nephropathy. Recently, we showed that combination therapy with an AT1 receptor blocker (ARB) and an activated vitamin D analog produced excellent synergistic effects against diabetic nephropathy, as a result of blockade of the ARB-induced compensatory renin increase. Given the diversity of vitamin D analogs, here we used a pro-drug vitamin D analog, doxercalciferol (1α-hydroxyvitamin D2), to further test the efficacy of the combination strategy in long-term treatment. Streptozotocin-induced diabetic DBA/2J mice were treated with vehicle, losartan, doxercalciferol (0.4 and 0.6 μg/kg), or losartan and doxercalciferol combinations for 20 wk. Vehicle-treated diabetic mice developed progressive albuminuria and glomerulosclerosis. Losartan alone moderately ameliorated kidney injury, with renin being drastically upregulated. A similar therapeutic effect was seen with doxercalciferol alone, which markedly suppressed renin and angiotensinogen expression. The losartan and doxercalciferol combination most effectively prevented albuminuria, restored glomerular filtration barrier structure, and dramatically reduced glomerulosclerosis in a dose-dependent manner. These effects were accompanied by blockade of intrarenal renin upregulation and ANG II accumulation. These data demonstrate an excellent therapeutic potential for doxercalciferol in diabetic renal disease and confirm the concept that blockade of the compensatory renin increase enhances the efficacy of RAS inhibition and produces synergistic therapeutic effects in combination therapy.

Long-Term Treatment of Sirolimus but Not Cyclosporine Ameliorates Diabetic Nephropathy in the Rat

2009 ◽  
Vol 87 (9) ◽  
pp. 1290-1299 ◽  
Author(s):  
Sandra Wittmann ◽  
Christoph Daniel ◽  
Andrea Stief ◽  
Regina Vogelbacher ◽  
Kerstin Amann ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Term Treatment ◽  
Long Term Treatment

scholarly journals Effect of silver nanoparticles on human mesenchymal stem cell differentiation

2014 ◽  
Vol 5 ◽  
pp. 2058-2069 ◽  
Author(s):  
Christina Sengstock ◽  
Jörg Diendorf ◽  
Matthias Epple ◽  
Thomas A Schildhauer ◽  
Manfred Köller
Keyword(s):  
Silver Nanoparticles ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Laser Scanning Microscopy ◽  
Surgical Instruments ◽  
Dependent Manner ◽  
Low Concentration ◽  
Long Term Treatment

Background: Silver nanoparticles (Ag-NP) are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter) were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (≥20 µg·mL−1 Ag-NP; ≥1.5 µg·mL−1 Ag+ ions) but not with low-concentration treatments (≤10 µg·mL−1 Ag-NP; ≤1.0 µg·mL−1 Ag+ ions). Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of specific biomarkers, including adiponectin (adipocytes) and osteocalcin (osteoblasts). Conclusion: Aside from the well-studied antibacterial effect of silver, little is known about the influence of nano-silver on cell differentiation processes. Our results demonstrate that ionic or nanoparticulate silver attenuates the adipogenic and osteogenic differentiation of hMSCs even at non-toxic concentrations. Therefore, more studies are needed to investigate the effects of silver species on cells at low concentrations during long-term treatment.

Efficacy and safety of long-term treatment with monthly calcifediol soft capsules in vitamin D deficient patients

2021 ◽  
Author(s):  
Jódar Esteban ◽  
Jose Luis Perez-Castrillon ◽  
Dueñas Antonio ◽  
Gonzalo Hernandez ◽  
Nieves Fernandez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Term Treatment ◽  
Efficacy And Safety ◽  
Long Term Treatment

scholarly journals Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e049104
Author(s):  
Shu Zhu ◽  
Lina Wu ◽  
Yongyu Mei ◽  
Zhihua Liu ◽  
Luping Lin ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Interferon Alpha ◽  
Controlled Study ◽  
Monotherapy Group ◽  
Ifn Alpha ◽  
Long Term Treatment ◽  
Randomised Controlled

IntroductionCombination antiviral therapy of nucleos(t)ide analogue (NA) and pegylated interferon alpha (peg-IFN alpha) decrease hepatitis B virus (HBV) surface antigen (HBsAg) levels to achieve functional cure and improve long-term prognosis in chronic hepatitis B patients. However, for hepatitis B-related liver fibrosis, studies on combination of these two medicines are limited. This study was designed to compare the efficacy between peg-IFN alpha combined with tenofovir (TDF) and TDF monotherapy for the clearance of HBsAg in NA-experienced patients with HBV-related liver fibrosis.Methods and analysisThis study was designed to be a prospective, multicentre, open, randomised controlled study. A total of 272 patients with HBV-related liver fibrosis will be randomised into the combination therapy group or the monotherapy group at a 1:1 ratio. Participants in the combination group will receive subcutaneous injections of peg-IFN alpha 180 µg per week for 48 weeks combined with oral TDF 300 mg daily. Participants in the monotherapy group will receive 300 mg oral TDF daily alone. All participants will undergo long-term treatment with TDF and will be followed up at the outpatient department for 144 weeks after randomisation. Clinical symptoms, laboratory tests and examination indicators will be collected at each follow-up time point, and adverse events will be recorded. The primary endpoint is serological clearance rate of HBsAg at 48 weeks.Ethics and disseminationThe ethics committee of the Third Affiliated Hospital at Sun Yat-sen University approved this study (Approval Number: (2020)02-183-01). The results of the study will be presented at relevant meetings and published in an appropriate journal after the completion of the trial and the analysis of the data.Trial registration numberNCT04640129.

Long-Term Treatment of Vitamin-D Resistant Rickets

1964 ◽  
Vol 46 (5) ◽  
pp. 978-997 ◽  
Author(s):  
DONALD S. PIERCE ◽  
WILLIAM M. WALLACE ◽  
CHARLES H. HERNDON
Keyword(s):  
Vitamin D ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Vitamin D Resistant Rickets ◽  
Resistant Rickets
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