TNF-α localization in the Dental Pulp of Albino Rats Receiving Long Term Treatment with Tramadol Hydrochloride

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline or dementia, the number of patients with AD is continuously increasing. Although a lot of great progress has been made in research and development of AD therapeutics, there is no fundamental cure for this disease yet. This study demonstrated the memory-improving effects of Cuban policosanol (PCO) in 5xFAD mice, which is an animal model of AD. Following 4-months of treatment with PCO in 5xFAD mice, we found that the number of amyloid plaques decreased in the brain compared to the vehicle-treated 5xFAD mice. Long-term PCO treatment in 5xFAD mice resulted in the reduction of gliosis and abnormal inflammatory cytokines level (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in the cortex and hippocampus. Levels of lipid peroxide (4-hydroxynonenal [4-HNE]) and superoxide dismutase (SOD1 and SOD2) levels were also recoverd in the brains of PCO-treated 5xFAD mice. Notably, PCO administration reduced memory deficits in the passive avoidance test, as well as synaptic loss (PSD-95, synaptophysin) in 5xFAD mice. Collectively, we identified the potential effects of PCO as a useful supplement to delay or prevent AD progression by inhibiting the formation of Aβ plaques in the brain.

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Invasive Trichophyton Rubrum Infection Occurring with Infliximab and Long-Term Prednisone Treatment

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2007.00009 ◽

2007 ◽

Vol 11 (2) ◽

pp. 84-88 ◽

Cited By ~ 18

Author(s):

Abigail L. Lowther ◽

Ally-Khan Somani ◽

Melissa Camouse ◽

Frances T. Florentino ◽

Stephen C. Somach

Keyword(s):

Trichophyton Rubrum ◽

Fungal Spores ◽

Giant Cells ◽

Invasive Disease ◽

Term Treatment ◽

Systemic Steroids ◽

Tnf Α ◽

Long Term Treatment ◽

Factor Α

Background: A 64-year-old woman presented with erythematous plaques, tender nodules, and pustules of the dorsal right hand and both legs following long-term treatment with systemic steroids and infliximab. Skin biopsy demonstrated dermal inflammation with foci of necrosis and multinucleated giant cells containing fungal spores. Tissue culture grew Trichophyton rubrum. Objective: To report a case that demonstrates the pathophysiology of invasive T. rubrum infection, the mechanisms of action and uses of tumor necrosis factor α (TNF-α)-inhibiting drugs, and how these drugs may increase patients' risk of invasive dermatophytosis. Conclusion: Dermatophytes such as T. rubrum rarely cause invasive disease. This unusual presentation of invasive T. rubrum occurred with immunosuppression by infliximab and systemic steroids. Patients should have a thorough examination for signs of latent infection before TNF-α inhibitors are prescribed, including inspection of the skin and nails for signs of dermatophytosis.

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Sulfasalazine Microparticles Targeting Macrophages for the Treatment of Inflammatory Diseases Affecting the Synovial Cavity

Pharmaceutics ◽

10.3390/pharmaceutics13070951 ◽

2021 ◽

Vol 13 (7) ◽

pp. 951

Author(s):

Monica-Carolina Villa-Hermosilla ◽

Ana Fernández-Carballido ◽

Carolina Hurtado ◽

Emilia Barcia ◽

Consuelo Montejo ◽

...

Keyword(s):

Adverse Effects ◽

Inflammatory Diseases ◽

Chronic Inflammatory Disease ◽

Term Treatment ◽

Particle Sizes ◽

Duration Of Action ◽

Tnf Α ◽

Long Term Treatment ◽

Inflammatory Processes

Rheumatoid arthritis (RA) is a chronic inflammatory disease with sulfasalazine (SSZ) extensively used for long-term treatment of both juvenile and adult RA. Its use is associated with adverse effects and toxicity due to its non-selective biodistribution. Macrophages play an important role in inflammatory processes. In order to target SSZ to macrophages in this work two microparticulate systems (MPs) are developed: SSZ-loaded PLGA MPs without and with α-tocopherol, with particle sizes lower than 5 μm and encapsulation efficiencies of 81.07 ± 11% and 63.50 ± 6.62%, respectively. Release of SSZ from MPs prepared with α-tocopherol was prolonged for 20 days. In RAW 264.7 cell macrophages MPs prepared with α-tocopherol were captured faster. Cell viability studies confirmed that SSZ-loaded MPs prepared without and with α-tocopherol did not produce cytotoxicity at the concentrations assayed. The anti-inflammatory activity of SSZ-loaded MPs was studied by quantifying interleukins IL-1, IL-6 and TNF-α in macrophages. All formulations produced a significant reduction of cytokine concentrations after 24 and 72 h, indicating that release of SSZ from the MPs was able to inhibit the inflammatory response induced by lipopolysaccharide (LPS). Gene expression of IL-1, IL-6 and TNF-α was decreased by SSZ-loaded MPs. SSZ-loaded MPs prepared with α-tocopherol will potentially allow increasing the residence time of SSZ in the synovial cavity, prolonging its duration of action, and reducing the adverse effects associated with its non-selective biodistribution.

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