Is dapsone still relevant in immune thrombocytopenia in resource limited settings?

Immune thrombocytopenia is an autoimmune disorder characterised by autoantibody production against platelets, increased platelet destruction and impaired thrombopoiesis. Steroids are the first-line agents whenever treatment is indicated; however, some patients may not respond and the responders may as well relapse while the dose is being tapered. Side effects of steroids prohibits their long-term use and patients often have to be switched to other agents. Standard drug management with intravenous immunoglobulins and thrombopoietin receptor analogues is difficult to administer in patients from low socioeconomic regions of the world making the management even more challenging. Hence, after reviewing the literature and considering the cost in comparison to all the second-line agents available, we tried dapsone in a steroid-dependent patient of immune thrombocytopenic purpura who had developed major steroid-related side effects. Patient showed good response to dapsone and has been in remission for around one and a half years.

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Emerging Therapies in Immune Thrombocytopenia

Journal of Clinical Medicine ◽

10.3390/jcm10051004 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1004

Author(s):

Sylvain Audia ◽

Bernard Bonnotte

Keyword(s):

Tyrosine Kinase ◽

Immune Thrombocytopenia ◽

Plasma Cells ◽

Autoimmune Disorder ◽

Intravenous Immunoglobulins ◽

Therapeutic Interventions ◽

Autoimmune Response ◽

Platelet Destruction ◽

Classical Complement Pathway ◽

Splenic Macrophages

Immune thrombocytopenia (ITP) is a rare autoimmune disorder caused by peripheral platelet destruction and inappropriate bone marrow production. The management of ITP is based on the utilization of steroids, intravenous immunoglobulins, rituximab, thrombopoietin receptor agonists (TPO-RAs), immunosuppressants and splenectomy. Recent advances in the understanding of its pathogenesis have opened new fields of therapeutic interventions. The phagocytosis of platelets by splenic macrophages could be inhibited by spleen tyrosine kinase (Syk) or Bruton tyrosine kinase (BTK) inhibitors. The clearance of antiplatelet antibodies could be accelerated by blocking the neonatal Fc receptor (FcRn), while new strategies targeting B cells and/or plasma cells could improve the reduction of pathogenic autoantibodies. The inhibition of the classical complement pathway that participates in platelet destruction also represents a new target. Platelet desialylation has emerged as a new mechanism of platelet destruction in ITP, and the inhibition of neuraminidase could dampen this phenomenon. T cells that support the autoimmune B cell response also represent an interesting target. Beyond the inhibition of the autoimmune response, new TPO-RAs that stimulate platelet production have been developed. The upcoming challenges will be the determination of predictive factors of response to treatments at a patient scale to optimize their management.

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Immune Thrombocytopenia Associated to Low-Dose Alemtuzumab Therapy in Chronic Lymphocytic Leukemia: A Single Retrospective Center Experience

Blood ◽

10.1182/blood.v120.21.4598.4598 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4598-4598

Author(s):

Gianluigi Reda ◽

Francesco Maura ◽

Giuseppe Gritti ◽

Daniele Vincenti ◽

Mariarita Sciumé ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Disease Progression ◽

Cumulative Dose ◽

Immune Thrombocytopenia ◽

Low Dose ◽

Conflicts Of Interest ◽

Autoimmune Disorder ◽

Intravenous Immunoglobulins ◽

Lymphocytic Leukemia ◽

Platelet Counts

Abstract Abstract 4598 Immune thrombocytopenia (ITP) is a common autoimmune complication in chronic lymphocytic leukemia (CLL), occurring in up to 5% of patients. The occurrence of alemtuzumab-associated ITP have been rarely reported in CLL and it has never been reported so far as a significant event complicating alemtuzumab treatment in clinical trials. Recently, a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab in a randomized, controlled phase II trial has been reported (Cuker et al, Blood 2011). We investigated the incidence of ITP in a cohort of 64 consecutive patients treated with low-dose alemtuzumab for relapsed/refractory CLL from 2003 to 2010. Subcutaneous alemtuzumab was administered at the dose of 10 mg three times a week, up to 18 weeks. ITP was documented in 12/64 patients: in 3 patients (4.7%) ITP developed before alemtuzumab treatment and no relapses of the autoimmune disorder were observed during the treatment; in 9 patients (14.8%, with an incidence of 5.7 events/100 patient-year) ITP developed after alemtuzumab treatment. Median time to ITP from initial alemtuzumab exposure was 12 months (range 1–42 months). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP onset, median platelet counts were 11×109/L (range 3–70) and anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. No patients showed severe or life-threatening bleeding. Three of nine patients who developed ITP after alemtuzumab therapy, experienced CLL progression requiring chemo-immunotherapy after 3, 4 and 13 months from ITP onset, respectively. One patient achieved a partial remission of CLL with ITP resolution, while the other two died of disease progression. In the remaining six cases, ITP was not associated with disease progression and was treated with corticosteroids and/or intravenous immunoglobulins. Five patients achieved normal platelet counts, while one patient did not respond. Low-dose alemtuzumab (theoretical cumulative dose 540 mg, equal to half of the classic cumulative dose and one-third of the individual dose) is an effective, safe and well tolerated treatment for CLL, as reported by several recent studies (Cortelezzi et al, Leukemia 2009; Brit J Haematol 2011). In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was 14.8% that is almost three times higher than previously reported in CLL. These data may indicate a role of T-lymphocyte dysregulation induced by alemtuzumab in the pathogenesis of ITP. Our data also suggested the importance of monitoring platelet counts during follow-up in patients treated with low-dose alemtuzumab for both haematological and non-haematological diseases. Disclosures: No relevant conflicts of interest to declare.

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Insilico analysis of acridone against TNF-α and PDE4 targets for the treatment of psoriasis

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl4.4286 ◽

2020 ◽

Vol 11 (SPL4) ◽

pp. 1251-1259

Author(s):

Sunitha Sukumaran ◽

Meghna M ◽

Sneha S ◽

Arjun B ◽

Sathianarayanan S ◽

...

Keyword(s):

Side Effects ◽

Active Sites ◽

Autoimmune Disorder ◽

Inflammatory Cells ◽

Dimethyl Fumarate ◽

Standard Drug ◽

Docking Score ◽

Tnf Α ◽

Standard Value ◽

Ligand Conformation

Psoriasis is an autoimmune disorder. Phosphodiesterase is a family of 1-11 among which PDE4 is most predominant enzymes present in inflammatory cells. Commercially available drugs are synthetic, and these may cause various side effects and are expensive. Dimethyl fumarate is the most frequently used systematic treatment for psoriasis with significant side effects such as myelosuppression, hepatic fibrosis and pulmonary fibrosis. Immune compromise drugs having various side effects, so this project is aimed to propose a novel drug that has more potency, efficiency and least side effects. The docking analysis was carried out to identify the best ligands by predicting the ligand conformation in the active protein sites and ligand binding affinity towards protein. Ligands were docked with the proteins, and all exhibited higher docking score than the standard drug dimethyl fumarate. The TNF- α inhibitors with PDB id such as 2ZJC, 2ZPX and PDE4 Inhibitors with PDB ID such as 3SL3, 1PTW are selected as target proteins, acridone had the best docking score of 19.3502 than standard value 12.997, and with PDB ID 3SL3, acridone showed 26.025 as docking score over the standard value 21.995. it interacted well with the active sites of the proteins. Thus, we infer that these studies will be a leader, in designing new and improved drug target for psoriatic therapy.

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Zastosowanie eltrombopagu w leczeniu przewlekłej małopłytkowości immunologicznej u dziecka – doświadczenia własne

Nowa Pediatria ◽

10.25121/np.2018.22.3.101 ◽

2018 ◽

Vol 22 (3) ◽

Author(s):

Anna Adamowicz-Salach ◽

Michał Matysiak

Keyword(s):

Immune Thrombocytopenia ◽

Autoimmune Disorder ◽

Intravenous Immunoglobulins ◽

Severe Form ◽

Small Subset ◽

Severe Thrombocytopenia ◽

Permanent Improvement ◽

Acute Form ◽

Clinically Significant ◽

Immune Thrombocytopenia Purpura

Immune thrombocytopenia purpura (ITP) is a rare autoimmune disorder but it is one of the most common bleeding disorder in childhood. Most children with this disease have acute form of ITP with self-limiting thrombocytopenia. A small subset of children with ITP has clinically significant disease with severe thrombocytopenia. We presented the case of a boy with a severe form of chronic immune thrombocytopenia who was treated for the first time six years before presented. At first autoimmunohemolytic anaemia was recognized. Next in therapeutic procedure, multi-drug treatment, including intravenous corticosteroids, intravenous immunoglobulins, and cyclosporine were used to achieve permanent improvement. Due to a chronic ITP and significant decrease platelets counts and severe symptoms of nose bleeding and anaemia, eltrombopag, thrombopoiesis stimulating factor, was used. After 16 weeks of treatment, as a result of triple therapy consisting of eltrombopag, prednisone and azathioprine, the platelets counts were normalized and the symptoms of bleeding resolved.

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Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190301150254 ◽

2019 ◽

Vol 19 (7) ◽

pp. 916-934 ◽

Cited By ~ 1

Author(s):

Appavoo Umamaheswari ◽

Ayarivan Puratchikody ◽

Natarajan Hari

Keyword(s):

Side Effects ◽

Inhibitory Activity ◽

Hydroxamic Acid ◽

Histone Deacetylase Inhibitors ◽

Therapeutic Potential ◽

In Vitro Assays ◽

Normal Cells ◽

Standard Drug ◽

In Silico Studies ◽

Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

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Perspectives on the Therapeutic Benefits of Arginine Supplementation in Cancer Treatment

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190116121451 ◽

2019 ◽

Vol 19 (7) ◽

pp. 913-920

Author(s):

Fabiani L. R. Beal ◽

Pedro R. Beal ◽

Juliana R. Beal ◽

Natan Carvalho-Neves ◽

Octávio L. Franco ◽

...

Keyword(s):

Amino Acid ◽

Side Effects ◽

Cancer Treatment ◽

Treatment Strategies ◽

Endothelial Permeability ◽

The Elderly ◽

Therapeutic Benefits ◽

Cell Growth And Differentiation ◽

The Cost ◽

Arginine Supplementation

Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. Objective: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. Results: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. Conclusion: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.

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Twitter Analysis of the Nonmedical Use and Side Effects of Methylphenidate, and User Sentiment about the Drug (Preprint)

10.2196/preprints.16466 ◽

2019 ◽

Author(s):

Jungu Kim ◽

Su Cheol Kim ◽

Jaegwon Jeong ◽

Myeong Gyu Kim

Keyword(s):

Side Effects ◽

Social Networking ◽

Brand Names ◽

Social Networking Services ◽

Hyperactivity Disorder ◽

Search Terms ◽

Nonmedical Use ◽

Twitter Analysis ◽

Sentiment Score ◽

The Cost

BACKGROUND Methylphenidate, a stimulant used to treat attention deficit hyperactivity disorder (ADHD), has the potential for nonmedical uses such as study and recreation. In the era of active use of social networking services (SNSs), experience with the nonmedical use or side effects of methylphenidate might be shared on Twitter. OBJECTIVE To analyze monthly tweets about methylphenidate, its nonmedical use and side effects, and user sentiments about methylphenidate. METHODS Tweets mentioning methylphenidate from August 2018 to July 2019 were collected using search terms for methylphenidate and its brand names. Only tweets written in English were included. The monthly number of tweets about methylphenidate and the number of tweets containing keywords related to the nonmedical use and side effects of methylphenidate were analyzed. Precision was calculated as the number of true nonmedical use or side effects divided by the number of tweets containing each keywords. Sentiment analysis was conducted using the text and emoji in tweets, and tweets were categorized as very negative (less than -3), negative (-3 to -1), neutral (0), positive (1 to 3), or very positive (more than 3), depending on the sentiment score. RESULTS A total of 4,169 tweets were ultimately selected for analysis. The number of tweets per month was lowest in August (n=264) and highest in May (n=435). There were 292 (7.0%) tweets about nonmedical uses of methylphenidate. Among those, 200 (4.8%) described use for studying, and 15 (0.4%) described use for recreation. In 91 (2.2%) tweets, snorting methylphenidate was mentioned. Side effects of methylphenidate, mainly poor appetite (n=74, 1.8%) and insomnia (n=54, 1.3%), were reported in 316 (7.6%) tweets. The average sentiment score was 0.027 ± 1.475, and neutral tweets were the most abundant (n=1,593, 38.2%). CONCLUSIONS Tweets about methylphenidate were most abundant in May, mentioned nonmedical use for study or recreation, and contained information about side effects. Analysis of Twitter has the advantage of saving the cost and time needed to conduct a survey, and could help identify nonmedical uses and side effects of drugs.

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A Population-Specific Optimized GeneXpert Pooling Algorithm for Chlamydia trachomatis and Neisseria gonorrhoeae To Reduce Cost of Molecular Sexually Transmitted Infection Screening in Resource-Limited Settings

Journal of Clinical Microbiology ◽

10.1128/jcm.00176-20 ◽

2020 ◽

Vol 58 (9) ◽

Author(s):

Sarah Connolly ◽

William Kilembe ◽

Mubiana Inambao ◽

Ana-Maria Visoiu ◽

Tyronza Sharkey ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Molecular Testing ◽

Resource Limited Settings ◽

Syphilis Infection ◽

Syndromic Management ◽

Sexually Transmitted ◽

Factors Associated ◽

Resource Limited ◽

The Cost ◽

Low Prevalence

ABSTRACT The sexually transmitted infections (STIs) chlamydia (CT) and gonorrhea (NG) are often asymptomatic in women and undetected by syndromic management, leading to complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Molecular testing, such as the GeneXpert CT/NG assay, is highly sensitive, but cost restraints preclude implementation of these technologies in resource-limited settings. Pooled testing is one strategy to reduce the cost per sample, but the extent of savings depends on disease prevalence. The current study describes a pooling strategy based on identification of sociodemographic and laboratory factors associated with CT/NG prevalence in a high-risk cohort of Zambian female sex workers and single mothers conducted from 2016 to 2019. Factors associated with testing positive for CT/NG via logistic regression modeling included city, younger age, lower education, long-acting reversible contraception usage, Trichomonas vaginalis infection, bacterial vaginosis, and incident syphilis infection. Based on these factors, the study population was stratified into high-, intermediate-, and low-prevalence subgroups and tested accordingly—individually, pools of 3, or pools of 4, respectively. The cost per sample was reduced from $18 to as low as $9.43 in the low-prevalence subgroup. The checklist tool and pooling approach described can be used in a variety of treatment algorithms to lower the cost per sample and increase access to molecular STI screening. This is particularly valuable in resource-limited settings to detect and treat asymptomatic CT/NG infections missed by traditional syndromic management.

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UJI AKTIVITAS EKSTRAK BUAS-BUAS (PREMNA SERRATIFOLIA LINN) SEBAGAI ANTI KOLESTEROL SECARA IN VITRO

AR-RAZI Jurnal Ilmiah ◽

10.29406/arz.v5i1.644 ◽

2017 ◽

Vol 5 (1) ◽

Author(s):

Dini Hadiarti

Keyword(s):

Solvent Extraction ◽

Side Effects ◽

Herbal Medicine ◽

Cholesterol Concentration ◽

Standard Curve ◽

Synthetic Drugs ◽

Standard Solution ◽

The Cost

ABSTRACTPremna Serratifolia Linn is believed to reduce cholesterol and as an alternative herbal medicine solution among the cost of medicine and the side effects caused by synthetic drugs. This study was conducted in several phases by using Premna Serratifolia Linn which was drained, mashed, and macerated using ethanol, choloform, and n-heksane. Extract obtained from evaporation, then whighed, and stored in a desiccators. Anti-cholesterol activity was tested test by using in vitro : began with determination of the maximum wavelength of the cholesterol standard solution with a UV-Vis spectrophotometer and continued by manufacturing the standard curve with the cholesterol concentration of 0.5; 0.75; 1; 1.25; and 1.5 mL and 1000 ppm cholesterol solution. Furthermore, maximum absorbance wavelength was measured in order to obtain the maximum wavelength of the cholesterol. The study reveled that the solvent extraction of ethanol produced the largest rendement. The extract Premna Serratifolia Linn is functioned as an anti-cholesterol. In addition, the absorbed reduction of 100 ppm cholesterol standard solution found in the addition of 0.5 mL choloform extract.Keywords: Anti-cholesterol, Premna Serratifolia Linn, In Vitro

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Involvement of Anti-Inflammatory, Antioxidant, and BDNF Up-Regulating Properties in the Antipsychotic-Like Effect of the Essential Oil of Alpinia Zerumbet in Mice: A Comparative Study With Olanzapine

10.21203/rs.3.rs-249536/v1 ◽

2021 ◽

Author(s):

Fernanda Yvelize Ramos de Araújo ◽

Adriano José Maia Chaves Filho ◽

Adriana Mary Nunes ◽

Gersilene Valente de Oliveira ◽

Patrícia Xavier Lima Gomes ◽

...

Keyword(s):

Weight Gain ◽

Drug Therapy ◽

Side Effects ◽

Essential Oil ◽

Negative Symptoms ◽

Repeated Administration ◽

Social Impairment ◽

Standard Drug ◽

Anti Inflammatory ◽

Alpinia Zerumbet

Abstract The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder’s cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we aimed to determine the effects of EAOZ in the prevention and reversal of schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. To this end, we evaluated antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

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