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

Pharmaceutics ◽  
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.

scholarly journals P709 Is azathioprine safe as long-term treatment in paediatric patients with inflammatory bowel disease?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S573-S573
Author(s):  
M A Martínez Ibeas ◽  
I Bacelo Ruano ◽  
S Rodríguez Manchón ◽  
M Velasco Rodríguez-Belvís ◽  
J F Viada Bris ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Side Effects ◽  
Adverse Effects ◽  
Term Treatment ◽  
Tpmt Activity ◽  
Duration Of Treatment ◽  
Median Dosage ◽  
Long Term Treatment ◽  
Inflammatory Bowel

Abstract Background The toxicity of azathioprine (AZA) includes myelosuppression, infections, pancreatitis, photosensitivity, and hepatotoxicity. The aim of this study was to describe the adverse effects profile of azathioprine as long-term treatment in paediatric inflammatory bowel disease (IBD). Methods An observational, descriptive and retrospective study was performed in the paediatric IBD Unit of a tertiary care hospital from September 2008 to December 2018. It was included patients under 18 diagnosed with IBD who were treated with AZA during their follow-up. We recorded epidemiological data, thiopurine methyltransferase (TPMT) enzyme activity, AZA side effects, and the dosage the patients were receiving when these effects took place. Bone marrow suppression (BMS) was defined as leukopenia, thrombocytopenia and/or anaemia. Acute pancreatitis (AP) induced by azathioprine was considered when two of these criteria (Atlanta 2012) were met: lipase increase (> 3 times normal value), congruent signs and symptoms and/or echographic findings, without other possible aetiology and with complete recovery after AZA withdrawal. Results We included 52 patients, being 31 men (59.6%). They were diagnosed with Crohn′s disease (CD) (73%), ulcerative colitis (UC) (21%) and IBD-unclassified (6%). The median TPMT activity was 17 U/ml (14.2–19.2). Up to 63.5% developed adverse effects by AZA with a median time from the beginning of treatment of 11.4 months (2.6–26.4) and a median dosage of 2 mg/kg/day (1.7–2.3). The most frequent side effect was BMS (52%). These patients had a median TPMT activity of 16.9 U/ml (14.2–18.9), the median duration of treatment was 14 months (3.9–27.7), and the median dosage was 2 mg/kg/d (1.8–2.5). BMS was more frequent in patients with UC (p 0.04) and longer treatment (p 0.08). No differences were found according to age, sex or TPMT activity. Up to 11.5% developed AP, the median duration of treatment until its appearance was 1.5 months (0.7–43.3) and the median dosage was 2 mg/kg/d (1.5–2.5). No differences were found related to age, sex, diagnosis or dosage. Other side effects were: 3 flu-like symptoms, 3 opportunistic infections, 2 hypertransaminasemia, and 1 patient with elevated pancreatic enzymes and hyperbilirubinemia. AZA was discontinued in 14 patients (43.8%): in 6 due to AP, in 4 due to severe lymphopenia, in 2 because of Epstein-Barr virus infection, in 1 due to flu-like symptoms and in 1 with several adverse effects. Conclusion More than half of the patients treated with AZA presented side effects, mainly BMS, although most of them were mild and temporary, and the withdrawal of the drug was not necessary. It seems that TPMT activity is not useful to predict BMS, but this adverse effect could be related to a longer treatment.

Galantamine in long-term treatment formild cognitive impairment: Efficacy and safety

2011 ◽  
Vol 26 (S2) ◽  
pp. 1296-1296
Author(s):  
J. Zarra ◽  
L. Schmidt ◽  
B. Grecco
Keyword(s):  
Cognitive Impairment ◽  
Adverse Effects ◽  
Acetylcholine Receptors ◽  
Well Being ◽  
Cognitive Disorder ◽  
Term Treatment ◽  
Open Label ◽  
Global Deterioration Scale ◽  
Long Term Treatment

IntroductionTo evaluate the efficacy of galantamine in patients with Mild Cognitive Impairment. So there is a possible benefit in the deficit in executive and cognitive cerebral function (cholinergic system) with treatment with Galantamine.PurposeGalantamine is a reversible, competitive cholinesterasa inhibitor that also allosterically modulates nicotine acetylcholine receptors. Inhibition of acetylcholinesterase, the enzyme responsible for hydrolisis of acetylcholine at the cholinergic cognitive impairment. To evaluate the efficacy, safety and tolerability of galantamine in long-term in Mild Cognitive Disorder.MethodsA multicenter, open label, prospective, observational study enrolled 1028 patients, more 55 years old with Mild Neurocognitive Disorder (DSM IV criteria), during 30 months of treatment with galantamine 16 mg./day. Assessments included the MMSE, CDR, ADAS-GOG, FAQ, GCI, Trail making test, Global Deterioration Scale, and UKU scale of Adverse Effects.ResultsA total 1028 outpatients were treated with 16 mg./day galantamine during 30 months, the therapeutic response evaluated with CDR, MMSE and the tests and scales of function cognitive measuring, GCI and UKU scale of adverse effects, comparing the baseline to final scores.ConclusionMild Cognitive Disorder is being examined, so there aren’t enought treatment for this. A long-term treatment (30 months) galantamine improves cognition and global function, behavioural symptoms and the general state well being of patients with MCD. With incidence of adverse effects not significant and a very good profile of safety, the final results of the study suggest that galantamine may be particularly appropiate in the Mild Cognitive Disorder.

scholarly journals Attention deficit and hyperactivity disorder in people with epilepsy: diagnosis and implications to the treatment

2010 ◽  
Vol 68 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Julio A.S. Koneski ◽  
Erasmo B. Casella
Keyword(s):  
Adverse Effects ◽  
Attention Deficit ◽  
Clinical Studies ◽  
Social Life ◽  
Term Treatment ◽  
Hyperactivity Disorder ◽  
The Social ◽  
Long Term Treatment ◽  
Epilepsy Diagnosis

The association between attention deficit and hyperactivity disorder (ADHD) and epilepsy can cause significant impact on the social life of affected individuals and their families. Clinical studies suggest that 30-40% of people with epilepsy also have ADHD. There are no studies which demonstrate that short or long-term treatment with methylphenidate increases the risk of seizures. Some studies attempt to relate drug interactions between methylphenidate and antiepileptic drugs, but adverse effects of methylphenidate have not been shown clearly. This review presents some neurobiological and physiopathogenic aspects, common to ADHD and epilepsy, from recent research studies, related to pharmacology, neuroimaging and electroencephalography. Possible risk of occurrence of seizures associated with the use of methylphenidate are also discussed.

scholarly journals Pediatric Atopic Dermatitis: Update on the Treatment Options

2020 ◽  
Vol 25 (4) ◽  
pp. 60-62
Author(s):  
Corina Adelina Zah ◽  
Andreea Emiliana Toporău ◽  
Paul Grama
Keyword(s):  
Atopic Dermatitis ◽  
Chronic Treatment ◽  
Pediatric Patients ◽  
Treatment Options ◽  
Chronic Inflammatory Disease ◽  
Term Treatment ◽  
Phosphodiesterase 4 ◽  
Systemic Corticosteroids ◽  
Long Term Treatment

Abstract Atopic dermatitis (AD) is a chronic inflammatory disease characterized by skin dryness, pruritus and eczematous lesions with various periods of relapse. Symptomatology can appear in childhood and can persist in adulthood. Chronic treatment is required with corticosteroids being the standard options. The side effects of this type of long-term treatment represent a major concern for the pediatric patients. This review aims to give an update of the options used for treatment, apart from the systemic corticosteroids. Mild-to-moderate AD had a good response to creams containing fig and oatmeal extracts and inhibitors of phosphodiesterase-4 (crisaborole). In cases of severe AD, future treatment options could include monoclonal antibodies such as omalizumab and dupilumab

scholarly journals Long-Term Treatment of Cuban Policosanol Attenuates Abnormal Oxidative Stress and Inflammatory Response via Amyloid Plaques Reduction in 5xFAD Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1321
Author(s):  
Jin-Ho Kim ◽  
Dong-Kyun Lim ◽  
Yoo-Hun Suh ◽  
Keun-A Chang
Keyword(s):  
Neurodegenerative Disorder ◽  
Lipid Peroxide ◽  
Amyloid Plaques ◽  
Term Treatment ◽  
Number Of Patients ◽  
Tnf Α ◽  
Long Term Treatment ◽  
5Xfad Mice ◽  
The Brain

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.

Adverse effects of dopamine potentiation by long-term treatment with selegiline

2003 ◽  
Vol 19 (1) ◽  
pp. 107-109 ◽  
Author(s):  
Susan Hollán ◽  
László Vécsei ◽  
Kálmán Magyar
Keyword(s):  
Adverse Effects ◽  
Term Treatment ◽  
Long Term Treatment

Long-term treatment of macroprolactinomas with CV 205-502

1993 ◽  
Vol 128 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Anette Kvistborg ◽  
Johan Halse ◽  
Soren Bakke ◽  
Trine Bjøro ◽  
Egill Hansen ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Adverse Reactions ◽  
Well Being ◽  
Term Treatment ◽  
Gonadal Function ◽  
Serious Adverse Events ◽  
Receptor Affinity ◽  
Discontinuation Of Treatment ◽  
Long Term Treatment

The long-term efficacy and tolerability of CV 205-502, a non-ergot dopamine agonist with D-2 receptor affinity, were studied for up to 36 months in 16 patients with macroprolactinomas. Prolactin values were reduced in all cases, becoming either normalized or suppressed in 12. The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects. Concomitantly we observed improvement in gonadal function, galactorrhea, headache, libido and general well-being. Adverse reactions were experienced by 1 5 patients during dosage increment and caused one patient to discontinue the medication. Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205-502, sufficient to normalize PRL levels in three. Two patients experienced serious adverse events, causing the discontinuation of treatment in one case. In eight patients treatment with CV 205-502 and bromocriptine could be compared. Three patients responded better to CV 205-502 than to bromocriptine treatment. Only one patient preferred bromocriptine to CV 205-502 for long-term treatment. We conclude that CV 205-502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas. CV 205-502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed.

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