scholarly journals Acitretin-Conjugated Dextran Nanoparticles Ameliorate Psoriasis-like Skin Disease at Low Dosages

2022 ◽  
Vol 9 ◽  
Author(s):  
Jiajia Lan ◽  
Yuce Li ◽  
Jingjing Wen ◽  
Yu Chen ◽  
Jing Yang ◽  
...  
Keyword(s):  
Side Effects ◽  
Skin Disease ◽  
Inhibitory Effect ◽  
Keratinocyte Proliferation ◽  
Psoriasis Treatment ◽  
Stat3 Phosphorylation ◽  
Term Administration ◽  
Dose Dependent ◽  
Systemic Drug

Psoriasis is a common chronic inflammatory skin disease mainly characterized by keratinocyte hyperproliferation and massive infiltration of inflammatory immune cells. Acitretin (ACT), an FDA-approved first-line systemic drug for psoriasis treatment, could suppress the proliferation of keratinocytes and downregulate the expression of inflammatory cytokines by modulating signal transducer and activator of transcription (STAT) signaling pathways. However, dose-dependent side effects of ACT limit its long-term administration in the clinic. Therefore, improving the therapeutic efficacy of ACT to reduce clinical dosage will benefit the patients. Here, we develop ACT-conjugated dextran nanoparticles (ACT-Dex NPs) and evaluated the potential for psoriasis treatment. Our results indicate that ACT-Dex NPs ameliorate psoriasis-like skin disease significantly at a low dosage which does not cause side effects, while neat ACT drugs at an equivalent dosage provide much less benefit. Moreover, we demonstrate that ACT-Dex NPs suppress keratinocyte proliferation more efficiently than neat ACT by enhancing the inhibitory effect on STAT3 phosphorylation. Thus, the proposed ACT-Dex NPs provide an effective and safe option for psoriasis treatment.

scholarly journals A review study of targeting of AAK1 and JAK1/2 using baricitinib in COVID-19 infected human cells

2020 ◽  
Vol 16 (supplement) ◽  
pp. 9-15
Author(s):  
Abeer M Al-Humaidhi
Keyword(s):  
Side Effects ◽  
Inhibitory Effect ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Pros And Cons ◽  
Experimental Trials ◽  
Pharmaceutical Agents ◽  
Dose Dependent ◽  
A Current

     The outbreak of a current public health coronavirus 2019 disease is a causative agent of a serious acute respiratory syndrome and even death. COVID-19 has exposed to multi-suggested pharmaceutical agents to control this global disease. Baricitinib, a well-known antirheumatic agent, was one of them. This article reviews the likely pros and cons of baricitinib in attenuation of COVID-19 based on the mechanism of drug action as well as its pharmacokinetics. The inhibitory effect of baricitinib on receptor mediated endocytosis promoter, AKK1, and on JAK-STAT signaling pathway is benefacial in inhibition of both viral assembling and inflammation. Also, its pharmacokinetic has encouraged the physicians toward the drug selection for COVID-19 treatment. On the other hand, most of baricitinib side effects are dose-dependent. In conclusion, targeting of AAK1 and JAK1/2 using baricitinib has predicted to be potential and effective with minimal side effects in management COVID-19 infected patients for a short therapeutic dosing period. Laboratory monitoring should be considered for some parameters. However, experimental trials are mandatory for a long-term treatment with a lower dose of baricitinib to evaluate its effectiveness and safety in patients with moderate COVID-19 infection.

scholarly journals A Review of the Treatment of Opioid-induced Constipation with Methylnaltrexone Bromide

2010 ◽  
Vol 2 ◽  
pp. CMT.S1168
Author(s):  
Francisco M. Abarca ◽  
Theodore J. Saclarides ◽  
Marc I. Brand
Keyword(s):  
Adverse Reaction ◽  
Side Effects ◽  
Severe Pain ◽  
Database Search ◽  
Mu Receptor ◽  
Quaternary Derivative ◽  
Term Administration ◽  
Data Source ◽  
Common Adverse Reaction

Objectives Review and summarize the mechanism of action of methylnaltrexone bromide (methylnaltrexone) and its effectiveness in the treatment of opioid-induced constipation. Data Source A multi-database search was conducted using PubMed and MEDLINE databases, in addition to electronic links to related articles and references. Background Opioids are effective medications for the management of moderate to severe pain, but they are associated with a number of side effects, especially within the gastrointestinal system. Constipation is a very common adverse reaction in patients with late-stage, adverse illness, who require long term administration of opioids on a chronic basis to help alleviate pain. In April 2008, the Food and Drug Administration approved the use of methylnaltrexone, a quaternary derivative of naltrexone which does not cross the blood brain barrier, for the management of patients with opioid-induced constipation. Methylnaltrexone acts as a selective peripheral Mu-receptor antagonist, without affecting the effects of opioids on central analgesia. Conclusions Studies have been shown that methylnaltrexone can be used safely in the treatment of opioid-induced constipation without either interfering with opioid effects on central anesthesia or precipitating opioid withdrawal.

scholarly journals Side-Effects of Long-Term Administration of Erlotinib in Patients with Non-small Cell Lung Cancer

2010 ◽  
Vol 5 (9) ◽  
pp. 1477-1480 ◽  
Author(s):  
Annemarie Becker ◽  
Atie van Wijk ◽  
Egbert F. Smit ◽  
Pieter E. Postmus
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Administration

scholarly journals Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

1994 ◽  
Vol 3 (7) ◽  
pp. S25-S30 ◽  
Author(s):  
A. F. Capristo ◽  
M. Miraglia del Giudice Jr ◽  
C. Alfaro ◽  
N. Maiello
Keyword(s):  
Side Effects ◽  
Combined Treatment ◽  
Provocation Test ◽  
Double Bind ◽  
Hypertonic Solution ◽  
Inflammatory Drugs ◽  
Bronchial Hyper Responsiveness ◽  
Sparing Effect ◽  
Dose Dependent

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use.

Long-Term Administration of Tianeptine in Depressed Patients after Alcohol Withdrawal

1992 ◽  
Vol 160 (S15) ◽  
pp. 66-71 ◽  
Author(s):  
R. Malka ◽  
H. Lôo ◽  
H. Ganry ◽  
A. Souche ◽  
C. Marey ◽  
...  
Keyword(s):  
Side Effects ◽  
Alcohol Withdrawal ◽  
Major Depressive Episode ◽  
Multicentre Trial ◽  
Dysthymic Disorder ◽  
Major Depressive ◽  
Depressed Patients ◽  
Term Administration ◽  
Neurochemical Effect

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.

scholarly journals Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A301-A302
Author(s):  
Troy Puar ◽  
Fengjie Tang ◽  
Lih-Ming Loh ◽  
Roger Foo ◽  
Wann Jia Loh ◽  
...  
Keyword(s):  
Side Effects ◽  
Medical Therapy ◽  
Primary Aldosteronism ◽  
Male Gender ◽  
Monitoring Strategy ◽  
Biochemical Control ◽  
Duration Of Treatment ◽  
Limited Efficacy ◽  
Dose Dependent

Abstract Introduction: Patients with primary aldosteronism (PA) have increased cardiovascular risk and studies have found that medical therapy fails to ameliorate this. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods: We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000–2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results: 53.7% of patients achieved blood pressure <140/90mmHg, 44.6% achieved serum potassium ≥4.3mmol/L, and 63.2% achieved renin levels >1ng/ml/hr. Concordance between biochemical control as assessed by potassium and renin levels was 49%. 45.3% of patients experienced side effects, with 8.5% switching to another medication, 18.9% decreasing dose, and 10.0% stopping medications altogether. Risk factors for side effects were spironolactone use, dose ≥50mg, duration of treatment ≥1 year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher median doses of spironolactone, 75mg vs 50mg, P<0.001, but more had persistent hypokalemia, 20.5% versus 6.4%, P=0.007. 44 patients with unilateral PA underwent surgery after initial medical therapy, which further improved systolic and diastolic BP, from 142 to 134mmHg, P<0.001, and from 85 to 79mmHg, P<0.001, respectively. Conclusion: Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. In patients with unilateral PA, surgery remains a better option compared to life-long medications.

scholarly journals The Bluegreen Algae (AFA) Consumption over 48 h Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood)

2020 ◽  
Vol 10 (2) ◽  
pp. 49
Author(s):  
José Joaquín Merino ◽  
María Eugenia Cabaña-Muñoz ◽  
María Jesús Pelaz
Keyword(s):  
Stem Cells ◽  
Side Effects ◽  
Healthy Subjects ◽  
Nutritional Supplementation ◽  
Double Blind Study ◽  
Short Term ◽  
Cd34 Cells ◽  
Term Administration ◽  
Bluegreen Algae

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA—Aphanizomenon flos aquae—algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 a.m.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects.

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