POSSIBLE ADVERSE EFFECTS OF ONCE-DAILY ORAL THERAPEUTIC DOSE OF EITHER GLUCOSAMINE SULFATE OR GLUCOSAMINE/CHONDROITIN SULFATE ON BLOOD CELLS COUNT IN RATS

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats

Lasers in Medical Science ◽

10.1007/s10103-017-2401-9 ◽

2017 ◽

Vol 33 (3) ◽

pp. 549-557 ◽

Cited By ~ 11

Author(s):

Marcella Sanches ◽

Lívia Assis ◽

Cyntia Criniti ◽

Danilo Fernandes ◽

Carla Tim ◽

...

Keyword(s):

Chondroitin Sulfate ◽

Experimental Model ◽

Morphological Changes ◽

Glucosamine Sulfate

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NORMAL GRANULOCYTE INFUSION THERAPY FOR ASPERGILLOSIS IN CHRONIC GRANULOMATOUS DISEASE

PEDIATRICS ◽

10.1542/peds.51.2.230 ◽

1973 ◽

Vol 51 (2) ◽

pp. 230-233

Author(s):

Andrew A. Raubitschek ◽

Alan S. Levin ◽

Daniel P. Stites ◽

Edward B. Shaw ◽

H. Hugh Fudenberg

Keyword(s):

Adverse Effects ◽

Chronic Granulomatous Disease ◽

Blood Cells ◽

White Blood Cells ◽

Infusion Therapy ◽

Granulomatous Disease ◽

Transient Improvement ◽

Life Threatening ◽

Granulocyte Function

An 8-year-old boy with chronic granulomatous disease (CGD) was admitted in moribund condition with aspergillus pneumonia. Because of the gravity of the situation, normal granulocyte infusions were used as adjuncts to the more conventional antimicrobial therapy. White blood cells, derived from a total of 58 units of whole blood obtained by leukophoresis of the father, were given in two separate doses. The first dose, totaling 2.8 x 1010 granulocytes, was coincident with significant improvement, and the second, totaling 3.0 x 1010 granulocytes, was coincident with the onset of clinical improvement and interim recovery. Transient improvement in in vitro granulocyte function was noted in cells taken from the patient's blood immediately after infusion. No adverse effects of the infusions were noted in either the patient or the donor. Although it is impossible to divorce the therapeutic effect of the granulocyte infusions from the more conventional therapy, we conclude that normal granulocyte infusions can be considered a valid adjunct in children with CGD who are suffering from a life-threatening infection.

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Activity of antioxidant enzymes in serum of rats under conditions of carrageenan-induced joint inflammation and prophylactic administration of chondroitin sulfate

Bulletin of Taras Shevchenko National University of Kyiv Series Biology ◽

10.17721/1728_2748.2020.81.46-49 ◽

2020 ◽

Vol 81 (2) ◽

pp. 46-49

Author(s):

L. Kot ◽

L. Yurchenko ◽

A. Shepeleva ◽

K. Dvorshchenko

Keyword(s):

Superoxide Dismutase ◽

Blood Serum ◽

Chondroitin Sulfate ◽

Catalase Activity ◽

Therapeutic Dose ◽

Joint Inflammation ◽

Joint Diseases ◽

Nacl Solution ◽

Prophylactic Administration ◽

Inflammatory Edema

Among the diseases of the musculoskeletal system, the leading place is occupied by joint diseases. It is important to conduct effective prevention of these diseases in order to stop or slow down the development of pathological changes in the body. In this regard, an important issue is the search for means to restore joints. Promising in the prevention and treatment of joint diseases is the use of chondroitin sulfate, which is a natural component of the intercellular substance of cartilage. The aim of this work was to investigate the prophylactic effect of chondroitin sulfate on the activity of superoxide dismutase and catalase in rat blood serum under conditions of carrageenan-induced joint inflammation. The studies were conducted on white non-linear, sexually mature male rats weighing 180–240 g, in compliance with the general ethical principles of experiments on animals. All animals were divided into four experimental groups. The first group – control: animals sub-planar injected 0.1 ml of 0,9 % NaCl solution into the posterior right limb. The second group – animals received a therapeutic dose of 3 mg x kg-1 chondroitin sulfate daily for 28 days daily. The third group – animals were infused intramuscularly with 0,1 ml of 0,9 % NaCl solution in the posterior right limb for 28 days and for 29 days inflammatory edema of the limb was stimulated (animals were sub-planar injected with 0,1 ml of 1% carrageenan solution to the posterior right limb ) The fourth group – for 28 days rats were daily intramuscularly injected with a therapeutic dose of 3 mg x kg-1 chondroitin sulfate, after which on 29th day, inflammatory edema of the limb was stimulated. The total number of animals involved in experimental studies was 40 individuals. Superoxide dismutase activity was assessed by the ability of the enzyme to compete with nitro blue tetrazolium for superoxide radicals. Catalase activity was measured by the amount of intact hydrogen peroxide in the sample. Protein content was measured by the Lowry method. It was revealed that under conditions of carrageenan-induced joint inflammation in the blood serum, the antioxidant defense system is disrupted: the activity of superoxide dismutase decreases by 1,5 times, while the catalase activity increases by 2,1 times compared to the control. Prophylactic administration of chondroitin sulfate to animals with carrageenan-induced joint inflammation contributes to the restoration of the antioxidant system.

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Topical Isotretinoin in Acne Vulgaris

TAJ Journal of Teachers Association ◽

10.3329/taj.v29i2.39099 ◽

2018 ◽

Vol 29 (2) ◽

pp. 1-5

Author(s):

M Moksedur Rahman ◽

M Abdullah ◽

M Moazzem Hossain ◽

MA Siddique ◽

M Nessa ◽

...

Keyword(s):

Side Effects ◽

Adverse Effects ◽

Prospective Study ◽

Acne Vulgaris ◽

Topical Therapy ◽

Outpatient Department ◽

College Hospital ◽

Once Daily ◽

Medical College ◽

Cutaneous Reactions

This study was carried out to evaluate the efficacy, safety and adverse effects of topical isotretinoin 0.05% gel in the treatment of acne vulgaris. This prospective study was undertaken in Skin & VD outpatient department of Rajshahi Medical College Hospital, Rajshahi. One hundred patients with mild tomoderate acne vulgaris were enrolled and were instructed to apply isotretinoin 0.05% gel once daily at night for 12 weeks. Patients were followed up at 2,4,8 and 12 weeks for efficacy and tolerability. Efficacy was measured by counting facial inflammatory and noninflammatory lesions and by grading acne severity. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus.Response was excellent in 80%of cases.None of the cutaneous reactions was severe, all were mild and well tolerated.Nobody had to discontinue the therapy for side effects. This study confirms that isotretinoin 0.05% gel is safe and effective topical therapy for mild to moderate acnevulgaris.TAJ 2016; 29(2): 1-5

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Retrospective Study of 122 Dogs That Were Treated with the Antifibrinolytic Drug Aminocaproic Acid: 2010–2012

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-6298 ◽

2016 ◽

Vol 52 (3) ◽

pp. 144-148 ◽

Cited By ~ 3

Author(s):

Megan Davis ◽

Kiko Bracker

Keyword(s):

Retrospective Study ◽

Adverse Effects ◽

Blood Cell ◽

Red Blood Cell ◽

Blood Cells ◽

Medical Records ◽

Aminocaproic Acid ◽

Red Blood Cell Transfusion ◽

Antifibrinolytic Drugs ◽

Red Blood Cell Transfusions

ABSTRACT Antifibrinolytic drugs are used to promote hemostasis and decrease the need for red blood cell transfusion. Medical records of 122 dogs that were prescribed either oral or intravenous aminocaproic acid between 2010 and 2012 were evaluated retrospectively. Of the 122 dogs, three experienced possible drug-related adverse effects. No significant differences were identified between dogs that experienced adverse effects and those that did not and the possible adverse effects noted were all minor. All dogs that received packed red blood cell transfusions were evaluated for correlations between baseline packed cell volume or dose of red blood cells and aminocaproic acid dose and no correlation was identified. Dogs that received aminocaproic acid as a treatment for active bleeding were divided by cause of hemorrhage into the following groups: neoplastic, non-neoplastic, and unknown. No significant differences in aminocaproic acid dose or the percentage of patients requiring a blood transfusion were identified between groups.

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Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose

Ghana Medical Journal ◽

10.4314/gmj.v43i3.55340 ◽

2010 ◽

Vol 43 (3) ◽

Cited By ~ 1

Author(s):

G.O Adjei ◽

B.Q Goka ◽

O.P Rodrigues ◽

L.C.G Hoegberg ◽

M Alifrangis ◽

...

Keyword(s):

Adverse Effects ◽

Therapeutic Dose

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Brigatinib: Novel ALK Inhibitor for Non–Small-Cell Lung Cancer

Annals of Pharmacotherapy ◽

10.1177/1060028018824578 ◽

2019 ◽

Vol 53 (6) ◽

pp. 621-626 ◽

Cited By ~ 7

Author(s):

Sara A. Spencer ◽

Angela C. Riley ◽

Adia Matthew ◽

Anthony J. Di Pasqua

Keyword(s):

Lung Cancer ◽

Adverse Effects ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

English Language ◽

Small Cell ◽

Small Cell Lung ◽

Once Daily ◽

Anaplastic Lymphoma ◽

Accelerated Approval

Objective: We review here the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions and place in therapy of brigatinib for abnormal anaplastic lymphoma kinase (ALK) specific non–small-cell lung cancer (NSCLC). Data Sources: A literature search using PubMed was conducted using the terms brigatinib and ALK positive NSCLC from January 2013 to November 2018. Study Selection and Data Extraction: All English-language articles evaluating brigatinib were analyzed for this review. Data Synthesis: Brigatinib was granted approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. It is administered at a dose of 90 mg orally once daily for the first 7 days then, if tolerated, increased to a dose of 180 mg orally once daily. Common adverse effects include nausea, fatigue, diarrhea, increased creatine phosphokinase levels, headache, dyspnea, and hypertension. Serious treatment-emergent adverse effects were pulmonary related. Relevance to Patient Care and Clinical Practice: This article discusses the clinical trials that led to the accelerated approval of brigatinib for its ability to overcome crizotinib-resistant mutations and for its increased central nervous system penetration properties. Conclusion: Brigatinib was granted accelerated approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. In a subset of NSCLC patients, brigatinib increases survival for approximately 1 year; however, side effects were detected.

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