scholarly journals Whole transcriptome in-silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects

2020 ◽  
Author(s):  
Yasaman Malekizadeh ◽  
Gareth Williams ◽  
Mark Kelson ◽  
David Whitfield ◽  
Jonathan Mill ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Influenza Infection ◽  
Drug Repurposing ◽  
Bioinformatic Analysis ◽  
New Information ◽  
Pdgfr Beta ◽  
Whole Transcriptome ◽  
First Time ◽  
Selenoamino Acid

AbstractINTRODUCTIONStroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.METHODWhole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository.RESULTSAtherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection).CONCLUSIONThese findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.COMPETING INTERESTSCB has received grants and personal fees from ACADIA Pharmaceuticals and Lundbeck, and personal fees from Heptares, Roche, Lilly, Otsuka, Orion, GlaxoSmithKline and Pfizer. DAC is an employee of Eli Lilly and Company Ltd.

scholarly journals Whole transcriptome in-silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects

2020 ◽  
Author(s):  
Yasaman Malekizadeh ◽  
Gareth Williams ◽  
Mark Kelson ◽  
David R Whitfield ◽  
Jonathan Mill ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Influenza Infection ◽  
Drug Repurposing ◽  
Bioinformatic Analysis ◽  
New Information ◽  
Pdgfr Beta ◽  
Whole Transcriptome ◽  
First Time ◽  
Selenoamino Acid

Abstract BACKGROUND Stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHODS Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository. RESULTS Atherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection). CONCLUSIONS These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.

scholarly journals ANALYSIS OF ADVERSE EVENTS AFTER IMMUNIZATION WITH VACCINES AGAINST Sars-Cov-2

World Science ◽  
2021 ◽  
Author(s):  
Stepanova H. M. ◽  
Shevchenko O. T. ◽  
Радзієвська Ірина Володимирівна
Keyword(s):  
Side Effects ◽  
Young People ◽  
Adverse Events ◽  
Muscle Pain ◽  
Adverse Reactions ◽  
Healthcare Professionals ◽  
Teaching Staff ◽  
New Information ◽  
Medical Academy ◽  
Local Side

Although the WHO-recommended coronavirus vaccines are safe and effective, vaccines provide new information to healthcare professionals about the extent and nature of adverse reactions to these drugs. The aim of the study is supplementing the available data on adverse reactions of vaccines on the example of the experience of vaccination of the teaching staff of the Cherkasy Medical Academy with vaccines COVISHIELD and COMIRNATY. Information for this study was collected retrospectively through a survey of 72 employees of the Cherkasy Medical Academy who were vaccinated with the COVISHIELD vaccine (first dose); 67 workers vaccinated with AstraZeneca (second dose); 54 workers who were vaccinated with COMIRNATY vaccine (first dose); 52 people vaccinated with this vaccine (second dose). The study confirmed that among the local side effects, the most common were pain at the injection site, among the systemic - fever, weakness, fatigue and drowsiness, headache, muscle pain, chills. Most of the side effects were most pronounced in young people, more often in women than in men.

scholarly journals Use of sodium-glucose co-transporter-2 inhibitors from clinical trial results to practical application in Russia

2018 ◽  
pp. 100-108
Author(s):  
D. A. Lebedev ◽  
A. Yu. Babenko
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Side Effects ◽  
Adverse Events ◽  
Female Gender ◽  
Clinical Trial Results ◽  
The Cost ◽  
First Time ◽  
Real Clinical Practice

In clinical trials of drugs, including sodium-glucose co-transporter-2 inhibitors (SGLT2), the main reason for the discontinuation of the therapy are side effects. However, there are additional factors that affect the discontinuation of the therapy in real clinical practice. This paper presents assessment of adverse events against the background of SGLT2 therapy with empagliflozin, identification of risk factors for these phenomena, and analysis of the reasons for discontinuation of SGLT2 therapy in real clinical practice. The study included 86 patients with type 2 diabetes mellitus, who were prescribed empagliflozin SGLT2 for the first time. During the trial, 24 (27.9%) cases of side effects were reported: infection in the genitourinary tract – 13 (15.1%) cases, hypoglycemia – 7 (8.1%) cases, and hypotension – 4 cases (4.7%). In general, the risk factors for adverse events were female gender, BMI ≥ 30 kg/m2 and reduced estimated glomerular filtration rate (eGFR<60 mL/min/1.73m2). The empaglyflosin therapy was discontinued in 37.1% of patients for the following reasons: the development of side effects – 11.6%, lack of efficacy of the therapy – 8.1%, the cost of the drug – 13.9%, other reasons – 3.5%. Thus, in real clinical practice, not only the development of side effects, but also socio-economic factors play an important role in supporting medication adherence.

A memoir of Hugh Miller (1802–1856) attributed to his son Hugh Miller FGS (1850–1896)

2017 ◽  
Vol 44 (1) ◽  
pp. 103-109 ◽  
Author(s):  
M. A. Taylor
Keyword(s):  
Family Member ◽  
New Information ◽  
Newspaper Editor ◽  
Interesting Contribution ◽  
First Time

A manuscript memoir of Hugh Miller (1802–1856), geologist, writer and newspaper editor, is attributed to his son Hugh Miller FGS (1850–1896). It is published here, apparently for the first time. It was written sometime in 1881–1896, more probably 1882–1895. Its intended place of publication is discussed. It is an interesting contribution to Miller biography, written by a family member and providing some new information and anecdotes.

Proton Pump Inhibitors in 2021: Pros, Cons, and Everything in Between

2021 ◽  
pp. 263451612110217
Author(s):  
Joshua A. Sloan ◽  
Philip O. Katz
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Adverse Events ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Drug Class ◽  
Life Threatening

The medical and lay literature has exploded with reports of adverse events associated with proton pump inhibitors over the last 10 to 15 years. The dissemination of these reports to patients and clinicians have created substantial concerns regarding what has been an exceptionally valuable drug class, dramatically improving patient quality of life, and in many cases preventing life threatening side effects of other medication. Patients are more frequently seeking to avoid these medications, and practitioners are reducing or discontinuing them to the patient’s detriment due to a misunderstanding of the data. This review will discuss the data regarding the most commonly publicized adverse events and attempt to put them in perspective.

scholarly journals Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110026
Author(s):  
Chinar R. Parikh ◽  
Jaya K. Ponnampalam ◽  
George Seligmann ◽  
Leda Coelewij ◽  
Ines Pineda-Torra ◽  
...  
Keyword(s):  
Side Effects ◽  
Clinical Efficacy ◽  
Inflammatory Arthritis ◽  
Biologic Agents ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Biologic Drugs ◽  
Therapeutic Implications ◽  
The Impact ◽  
First Time

The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.

scholarly journals High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni

2021 ◽  
Author(s):  
Annika S. Mokosch ◽  
Stefanie Gerbig ◽  
Christoph G. Grevelding ◽  
Simone Haeberlein ◽  
Bernhard Spengler
Keyword(s):  
Schistosoma Mansoni ◽  
Egg Production ◽  
Drug Repurposing ◽  
Cancer Drug ◽  
Ionization Mass ◽  
Parasitic Flatworm ◽  
Paired Female ◽  
First Time ◽  
Organ Tropism

AbstractSchistosoma mansoni is a parasitic flatworm causing schistosomiasis, an infectious disease affecting several hundred million people worldwide. Schistosomes live dioeciously, and upon pairing with the male, the female starts massive egg production, which causes pathology. Praziquantel (PZQ) is the only drug used, but it has an inherent risk of resistance development. Therefore, alternatives are needed. In the context of drug repurposing, the cancer drug imatinib was tested, showing high efficacy against S. mansoni in vitro. Besides the gonads, imatinib mainly affected the integrity of the intestine in males and females. In this study, we investigated the potential uptake and distribution of imatinib in adult schistosomes including its distribution kinetics. To this end, we applied for the first time atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) for drug imaging in paired S. mansoni. Our results indicate that imatinib was present in the esophagus and intestine of the male as early as 20 min after in vitro exposure, suggesting an oral uptake route. After one hour, the drug was also found inside the paired female. The detection of the main metabolite, N-desmethyl imatinib, indicated metabolization of the drug. Additionally, a marker signal for the female ovary was successfully applied to facilitate further conclusions regarding organ tropism of imatinib. Our results demonstrate that AP-SMALDI MSI is a useful method to study the uptake, tissue distribution, and metabolization of imatinib in S. mansoni. The results suggest using AP-SMALDI MSI also for investigating other antiparasitic compounds and their metabolites in schistosomes and other parasites. Graphical abstract

scholarly journals Efficacy and Safety of Modified Huang-Lian-Jie-Du Decoction Cream on Cancer Patients with Skin Side Effects Caused by EGFR Inhibition

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1081
Author(s):  
Ming-Yang Lee ◽  
Mei-Yi Lin ◽  
Yu-Ju Chang ◽  
Yu-Ting Tseng ◽  
I-An Huang ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Target Therapy ◽  
Herbal Medicines ◽  
Skin Toxicity ◽  
Dry Skin ◽  
Egfr Inhibition ◽  
The Mean ◽  
Skin Conditions

(1) Background: The epidermal growth factor inhibitors (EGFRIs)/tyrosine kinase inhibitors (TKIs) are effective for cancer target therapy, but acneiform rashes or so-called inflammatory papulopustular exanthemas are common (50% to 90%). The conventional therapy for EGFRIs/TKIs-induced skin toxicity is steroids and antibacterial drugs, but it is still ineffective for some patients, and EGFRIs/TKIs dose reduction/interruption may be needed. In this study, a modified Chinese herbal medicine, Huang-Lian-Jie-Du decoction cream with Yin-Cold (YC) medicine characteristic, was investigated for the effect on patients suffering EGFRIs/TKIs-induced skin toxicity. (2) Methods: The modified Huang-Lian-Jie-Du (mHLJD) decoction cream was made from 10 herbal medicines, including 4 major medicines (Huanglian, Huangqin, Huangbo, and Zhizi) in traditional HLJD decoction. Patients with EGFRIs/TKIs-induced skin toxicity were enrolled. Patients were excluded if they also used other cream for skin toxicity. Skin conditions were monitored by follow up every 2 weeks. The patients’ characteristics, the skin toxicities, treatment response, and adverse events were recorded and analyzed until skin problems resolved or the study ended. (3) Results: The mHLJD decoction cream and its sub-packages were stored at 4 °C before use. Thirty-four patients who had grade 1–3 skin toxicities after receiving EGFRIs/TKIs were enrolled. Seven patients withdrew or were excluded. Finally, data from 27 patients were analyzed. The mean grade of rash acneiform was significantly decreased from 2.19 (ranged 1 to 3) to 0.88 (ranged 0 to 2) after mHLJD decoction cream treatment for 4 weeks and to 0.55 (ranged 0 to 2) after mHLJD decoction cream treatment for 8 weeks. Additionally, the mean grade of dry skin was also significantly decreased from 1.57 (ranged 1 to 2) to 0.71 (ranged 0 to 1) after mHLJD decoction cream treatment for 4 weeks. The changes of skin toxicity were significant, with no obvious adverse events. (4) Conclusions: In summary, the mHLJD decoction cream provides benefits for alleviation of EGFRIs/TKIs-induced skin rash acneiform and dry skin. Additionally, no obvious side effects were found in patients using mHLJD decoction cream.

Tocilizumab in Giant Cell Arteritis: A Multicenter Retrospective Study of 34 Patients

2016 ◽  
Vol 43 (8) ◽  
pp. 1547-1552 ◽  
Author(s):  
Alexis Régent ◽  
Serge Redeker ◽  
Alban Deroux ◽  
Pierre Kieffer ◽  
Kim Heang Ly ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Adverse Events ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Multicenter Study ◽  
Efficacy And Safety ◽  
Severe Adverse Events ◽  
Retrospective Multicenter Study

Objective.To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA).Methods.A retrospective multicenter study that included 34 patients receiving TCZ for GCA.Results.TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 ± 1.3 months.Conclusion.TCZ is effective in GCA. However, side effects occur. Whether this treatment has only a suspensive effect remains to be determined.

Sign in / Sign up

Export Citation Format

Share Document