Mater Today Bio. 2021 Nov 12;12:100157. doi: 10.1016/j.mtbio.2021.100157. eCollection 2021 Sep.

ABSTRACT

Drug-induced liver injury (DILI) is a challenging clinical problem with respect to both diagnosis and management. As a newly emerging biomarker of liver injury, miR122 shows great potential in early and sensitive in situ detection of DILI. Glycyrrhetinic acid (GA) possesses desirable therapeutic effect on DILI, but its certain dose-dependent side effects after long-term and/or high-dose administration limit its clinical application. In this study, in order to improve the precise diagnosis and effective treatment of DILI, GA loaded all-in-one theranostic nanoplatform was designed by assembling of upconversion nanoparticles and gold nanocages. As a proof of concept, we demonstrated the applicability of this single-wavelength laser-triggered theranostic nanoplatform for the spatiotemporally controllable in situ imaging of DILI and miR122-controlled on-demand drug release in vitro and in vivo. This novel nanoplatform opens a promising avenue for the clinical diagnosis and treatment of DILI.

PMID:34825161 | PMC:PMC8604687 | DOI:10.1016/j.mtbio.2021.100157

Drug Ther Bull. 2021 Dec;59(12):184. doi: 10.1136/dtb.2021.000062.

ABSTRACT

Overview of: Medicines and Healthcare products Regulatory Agency. Topical corticosteroids: information on the risk of topical steroid withdrawal reactions. Drug Safety Update 2021;15(2):1.

PMID:34824131 | DOI:10.1136/dtb.2021.000062

J Palliat Care. 2021 Nov 25:8258597211030382. doi: 10.1177/08258597211030382. Online ahead of print.

ABSTRACT

INTRODUCTION: Skin disorders and neuropathy often occur as side effects of chemotherapy. We encountered a patient who was treated for drug-induced skin symptoms, but the symptoms did not improve, and he was eventually diagnosed as having dermatomyositis.

CASE PRESENTATION: A 71-year-old man underwent chemotherapy with regorafenib in February 2020 for the postoperative recurrence of sigmoid colon cancer, but treatment was discontinued after about 2 months owing to the appearance of skin symptoms, which were thought to be side effects of regorafenib. Subsequently, his symptoms further worsened, and he was hospitalized 3 weeks after the appearance of the initial skin symptoms, and a palliative care team was asked to relieve his back pain caused by the drug-induced skin symptoms. Erythema was widely observed on the lower back and limbs, and he experienced needle stick-like pain. Furthermore, the patient demonstrated difficulty in lifting both upper limbs. As acetaminophen was effective for his pain, the dose was slowly increased with careful observation. The cause of the patient's muscle weakness was unclear, and after careful discussion of the possible causes among specialists in dermatology, neurology, and rheumatoid arthritis, a diagnosis of dermatomyositis associated with the malignant tumor was made about 10 days after his admission. The patient's symptoms gradually improved with steroid pulse treatment (methylprednisolone 1 g/day for 3 days) followed by high-dose gamma globulin treatment (2.5 g/day for 5 days), and the patient was discharged 48 days after admission.

DISCUSSION: Because this patient was referred to a palliative care team for the purpose of relieving pain caused by skin symptoms associated with chemotherapy, a crucial point is the symptoms were treated as side effects of the chemotherapy from the beginning. As neuropathy can occur as a result of chemotherapy, the pain and muscle weakness could be explained at the time; however, the symptoms continued to worsen even after the chemotherapy was stopped. Because the symptoms were not typical of polymyositis/dermatomyositis, diagnosis of the patient was delayed, even though he was treated in each specialized department. Our present case indicates that paraneoplastic syndrome should always be kept in mind when treating cancer patients.

PMID:34823395 | DOI:10.1177/08258597211030382

Sci Rep. 2021 Nov 24;11(1):22848. doi: 10.1038/s41598-021-01930-y.

ABSTRACT

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.

PMID:34819514 | PMC:PMC8613264 | DOI:10.1038/s41598-021-01930-y

Cureus. 2021 Oct 23;13(10):e18985. doi: 10.7759/cureus.18985. eCollection 2021 Oct.

ABSTRACT

Vaccination is now considered the best measure in minimizing the morbidity and mortality from the Covid-19 pandemic. Almost all the vaccines are considered safe except for minor and occasional side effects. Some of the commonly reported complications from the COVID-19 vaccines are vaccine-induced thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome/vaccine-induced pro-thrombotic immune thrombocytopenia syndrome. In this case report, we present a case of a 75-year-old female who had an uncomplicated first and second vaccine dose but developed VITT after the booster dose of the vaccine. The patient was treated with dexamethasone and platelet transfusions. So far no such cases have been reported after the third (booster) dose of the Pfizer-Biontech vaccine. With this case report, we present the case of the patient and discuss the literature related to vaccine-induced thrombocytopenia.

PMID:34820240 | PMC:PMC8607313 | DOI:10.7759/cureus.18985

World Allergy Organ J. 2021 Nov 5;14(11):100602. doi: 10.1016/j.waojou.2021.100602. eCollection 2021 Nov.

ABSTRACT

BACKGROUND: The diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use.

METHODS: In this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR.

RESULTS: 175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2-67] to 23.5% [95%CI 9.6-47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1-28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6-41.9] vs. >3d: 11.6% [95%CI 6.0-21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%.

CONCLUSION: In most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

PMID:34820050 | PMC:PMC8585645 | DOI:10.1016/j.waojou.2021.100602

BMC Cancer. 2021 Nov 24;21(1):1269. doi: 10.1186/s12885-021-08973-4.

ABSTRACT

BACKGROUND: Entinostat is an oral inhibitor of class I histone deacetylases intended for endocrine therapy-resistant patients with hormone receptor-positive (HR+) advanced or metastatic breast cancer (BC). We examined the safety, efficacy, and pharmacokinetics of entinostat monotherapy and combined entinostat/exemestane in Japanese patients.

METHODS: This phase 1 study (3 + 3 dose-escalation design) enrolled postmenopausal women with advanced/metastatic HR+ BC previously treated with nonsteroidal aromatase inhibitors. Dose-limiting toxicities (DLTs) of entinostat monotherapy (3 mg/qw, 5 mg/qw, or 10 mg/q2w) and entinostat+exemestane (5 mg/qw + 25 mg/qd) were assessed. Pharmacokinetics, lysine acetylation (Ac-K), and T-cell activation markers were measured at multiple time points.

RESULTS: Twelve patients were enrolled. No DLTs or grade 3-5 adverse events (AEs) occurred. Drug-related AEs (≥ 2 patients) during DLT observation were hypophosphatemia, nausea, and platelet count decreased. Six patients (50%) achieved stable disease (SD) for ≥ 6 months, including one treated for > 19 months. Median progression-free survival was 13.9 months (95% CI 1.9-not calculable); median overall survival was not reached. Area under the plasma concentration-time curve and Ac-K in peripheral blood CD19+ B cells increased dose-proportionally. The changing patterns of entinostat concentrations and Ac-K levels were well correlated. T-cell activation markers increased over time; CD69 increased more in patients with SD ≥ 6 months vs. SD < 6 months.

CONCLUSIONS: Entinostat monotherapy and combined entinostat/exemestane were well tolerated in Japanese patients, with no additional safety concerns compared with previous reports. The correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, and also T-cell activation markers, merits further investigation.

TRIAL REGISTRATION: JAPIC Clinical Trial Information, JapicCTI-153066 . Registered 12 November 2015. ClinicalTrials.gov, NCT02623751 . Registered 8 December 2015.

PMID:34819039 | DOI:10.1186/s12885-021-08973-4

CNS Neurol Disord Drug Targets. 2021 Nov 23. doi: 10.2174/1871527320666211124093345. Online ahead of print.

ABSTRACT

BACKGROUND: Attention Deficit Hyperactivity Disorder is a common child neurobehavioral disorder whose pathogenesis is not completely understood. However, some evidence indicates a crucial link between this disorder and the degree of oxidative stress. Coenzyme Q10 (ubiquinol) is an antioxidant that may play a significant role in the treatment of Attention Deficit Hyperactivity Disorder.

OBJECTIVE: To assess the safety and efficacy of coenzyme Q10 as an add-on drug treatment for attention deficit hyperactivity disorder.

METHOD: Sixty children, aged 6-16 years, with attention deficit hyperactivity disorder, non-responders to atomoxetine treatment for 6 months, were included in this double-blind, randomized, and controlled study. Group 1 received atomoxetine plus coenzyme Q10, and group 2 received atomoxetine plus placebo for 6 months. Follow-up by CONNERS parent rating scale questionnaire (CPRS-48) was performed before and after 1, 3, and 6 months of treatment, and any drug-related side effects were reported.

RESULTS: The addition of coenzyme Q10 to atomoxetine in group 1 improved symptoms in a shorter time with minimal adverse effects. Group 1 showed improvement of about 33.87% in CPRS-48 total score versus 18.24% in group 2. There was a statistically significant decrease in CPRS-48 total score and its three subscales (learning problems, impulsive hyperactive subscale, and 10-items hyperactivity index) in group 1 versus group 2 after six months of treatment (p-value <0.001).

CONCLUSION: Coenzyme Q10 has an important role as an add-on drug treatment for attention deficit hyperactivity disorder by improving symptoms, particularly hyperactivity, and in minimizing atomoxetine adverse effects.

PMID:34819012 | DOI:10.2174/1871527320666211124093345

PLoS One. 2021 Nov 24;16(11):e0260656. doi: 10.1371/journal.pone.0260656. eCollection 2021.

ABSTRACT

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

PMID:34818379 | PMC:PMC8612507 | DOI:10.1371/journal.pone.0260656

Curr Neurol Neurosci Rep. 2021 Nov 24;21(12):66. doi: 10.1007/s11910-021-01151-w.

ABSTRACT

PURPOSE OF REVIEW: To review the neurologic complications of systemic anti-cancer therapies and radiation therapy.

RECENT FINDINGS: Although many of the newer systemic therapies have more favorable side effect profiles than traditional cytotoxic chemotherapy, neurotoxicity has been seen with some of newer targeted therapies, immunotherapy, and T cell engaging therapies, including CAR-T therapy. The most recent advances in radiation-induced neurotoxicity have focused on the prevention and the management of cognitive dysfunction, a known long-term complication of brain irradiation. Cancer therapies can damage both the central and the peripheral nervous systems, and the damage may not always be reversible. Neurologists and oncologists must be aware of the neurotoxicities associated with newer treatments, particularly CAR-T therapy and immunotherapy. Early recognition and appropriate management can help minimize neurologic injury.

PMID:34817688 | DOI:10.1007/s11910-021-01151-w

Cad Saude Publica. 2021 Nov 22;37(11):e00237221. doi: 10.1590/0102-311X00237221. eCollection 2021.

NO ABSTRACT

PMID:34816955 | DOI:10.1590/0102-311X00237221

Cad Saude Publica. 2021 Nov 22;37(11):e00228121. doi: 10.1590/0102-311X00228121. eCollection 2021.

NO ABSTRACT

PMID:34816954 | DOI:10.1590/0102-311X00228121

Int J Clin Pract. 2021 Nov 23:e15008. doi: 10.1111/ijcp.15008. Online ahead of print.

ABSTRACT

AIMS: Preoperative anxiety, which can affect post-operative recovery, is often present in patients undergoing surgery under loco-regional anesthesia (LRA). Minimizing preoperative anxiety with premedication can be effective but results in drug-related side effects. Therefore, the use of non-pharmacological techniques should be encouraged.

METHODS: We evaluated whether a Virtual Reality (VR) incorporating music and a hypnosis session, provided during the performance of LRA, can reduce preoperative anxiety. Fifty patients scheduled for elective hand surgery under an axillary plexus block were enrolled (March-June 2019). The primary outcome measure was the change in the Amsterdam Anxiety and Preoperative Information Scale (APAIS) questionnaire 5 minutes after the VR session as compared to before the VR session. The secondary outcome measures were the visual analog scale (VAS) for anxiety before and two hours after the surgery and the Evaluation du Vécu de l'ANesthésie - LocoRégionale (EVAN-LR) satisfaction score.

RESULTS: Data from 48 patients were analyzed. The APAIS score as well as VAS for anxiety were significantly reduced after a VR session (P < 0.001 for both scores). Patients were very satisfied (EVAN-LR: 92 (88, 94)).

CONCLUSIONS: The use of VR incorporating music and a hypnosis session could be an effective tool in the management of patient's preoperative anxiety during the performance of an axillary plexus block.

PMID:34811860 | DOI:10.1111/ijcp.15008

Curr Drug Saf. 2021 Nov 22. doi: 10.2174/1574886316666211122125215. Online ahead of print.

ABSTRACT

BACKGROUND: DIGO or drug-induced gingival overgrowth occurs as a side effect of certain drugs. Until now, the etiology of drug-induced gingival overgrowth is not clearly understood. Among the calcium channel blockers, nifedipine has been shown to be most frequently associated with drug-induced gingival hyperplasia. Amlodipine is a comparatively newer calcium channel blocker that witha longer duration of action and lesser side effects as compared to nifedipine. There are only certain case reports of amlodipine-induced gum hyperplasia.

CASE PRESENTATION: We report a case of amlodipine-induced gum hyperplasia in a 66-year-old hypertensive patient taking amlodipine at a dose of 5 mg once a day. There was significant regression of gum hypertrophy after substitution of amlodipine by Losartan.

CONCLUSION: Amlodipine is one of the commonly prescribed antihypertensive drugs, and gingival hyperplasia is one overlooked side effect in patients taking amlodipine. Awareness of this potential side effect of amlodipine may be helpful to reduce the anxiety of patients and the cost of diagnostic procedures.

PMID:34809550 | DOI:10.2174/1574886316666211122125215

Front Med (Lausanne). 2021 Nov 5;8:732727. doi: 10.3389/fmed.2021.732727. eCollection 2021.

ABSTRACT

Background: Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor (HDACi) romidepsin was approved for relapsed and refractory (R/R-PTCL) in 2011. This meta-analysis was performed to assess the efficacy and safety of romidepsin in PTCL. Methods: We searched for articles on the HDAC inhibitor romidepsin in the treatment of PTCL in Embase, Web of Science, and PubMed. The methodology is further detailed in PROSPERO (CRD42020213651, CRD42020213553). The 2-year overall survival (OS), 2-year progression-free survival (PFS), and their corresponding to 95% confidence intervals (CIs) were measured. Besides, corresponding 95% CIs were pooled for the complete response (CR), partial response (PR), duration of response (DoR), and risk of adverse events (AEs). Results: Eleven studies containing 388 patients were incorporated into the quantitative synthesis, of which R/R-PTCL patients were the dominant portion, accounting for 94.3% (366/388). For all studies, the CR rate was 20% (95% CI, 13-27%, random effects model), and the PR rate was 18% (95% CI, 12-25%, random effects model). The 2-year OS was 48% (95% CI, 38-59%, fixed effects model), and the 2-year PFS was 17% (95% CI, 13-21%, fixed effects model). There were no significant differences between romidepsin monotherapy and romidepsin plus additional drugs. Hematological toxicities, such as lymphopenia and granulocytopenia, remained the most continually happening grade 3 or higher AEs, accounting for 46 and 28%, respectively. None of the studies reported any drug-related mortality. Conclusions: Considering that most of the included patients had R/R-PTCL, the addition of romidepsin significantly enhance the efficacy. And AEs were tolerable as the grade 3/4 AEs in romidepsin monotherapy was 7% (95% CI, 6-8%). It is imperative to further expand the first-line application of romidepsin and carry out personalized therapy based on epigenomics, which will improve the survival of PTCL patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213651 and https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213553.

PMID:34805202 | PMC:PMC8602095 | DOI:10.3389/fmed.2021.732727

J Cardiovasc Pharmacol. 2021 Nov 17. doi: 10.1097/FJC.0000000000001182. Online ahead of print.

ABSTRACT

Cancer therapy has made major progress in the last several decades, but treatments are often accompanied by significant side effects. Arrhythmias are a widespread complication of some antineoplastic drugs, with atrial fibrillation (AF) being the most often encountered drug-associated arrhythmia. Preexisting AF risk factors are commonly present in cancer patients who develop drug-associated AF, and active cancer itself may cause or promote AF. While anticancer drugs may induce AF in cancer patients without AF risk factors, it appears that most drug-associated AF develop when cancer drugs add or aggravate pre-cancer-existing and/or cancer-related pro-AF factors/alterations, additively or synergistically producing AF. Abnormalities in intracellular calcium activity seem to be involved in the generation of anticancer drug-induced AF. In cancer survivors with cancer therapy-induced cardiomyopathy, AF often occurs, with most of the arrhythmias likely to develop secondary to the cardiomyopathy. AF may lead to modification or even cessation of cancer therapy. The management of AF in patients with cancer is currently conducted largely based on pragmatic assumptions. This review briefly discusses AF caused by anticancer drugs and the underlying mechanisms.

PMID:34803149 | DOI:10.1097/FJC.0000000000001182

Crit Rev Oncol Hematol. 2021 Dec;168:103533. doi: 10.1016/j.critrevonc.2021.103533. Epub 2021 Nov 19.

ABSTRACT

Over the past decade, the prognosis of advanced thyroid cancer (TC) patients has dramatically improved thanks to the introduction of tyrosine kinase inhibitors (TKIs). Despite their effectiveness, these drugs are burdened with several side effects that can negatively affect quality of life and compromise therapy continuation. Among renal adverse events (RAEs), proteinuria is the most frequently reported in clinical trials and real-life experiences, especially during treatment with lenvatinib or cabozantinib. This peculiar toxicity is commonly associated with targeted therapies with anti-angiogenic activity, even if the mechanisms underlying its onset and progression are not entirely clear. RAEs should be early recognized and properly managed to avoid renal function worsening and life-threatening consequences. Aiming at providing a comprehensive summary that can help clinicians to identify and manage TKIs-related RAEs in TC patients, we reviewed the current evidence about this topic, from pathogenesis and potential risk factors to diagnosis and treatment.

PMID:34801702 | DOI:10.1016/j.critrevonc.2021.103533

Addict Biol. 2021 Nov 21:e13117. doi: 10.1111/adb.13117. Online ahead of print.

ABSTRACT

Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP-1 analogue, liraglutide (LIR), in reducing heroin addiction-like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self-administration, prevents escalation of heroin self-administration and reduces drug-induced reinstatement of heroin-seeking behaviour in rats. A 1-h pretreatment time, however, was too short to reduce cue-induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR-paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin-naïve or heroin-experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.

PMID:34802173 | DOI:10.1111/adb.13117

Arch Toxicol. 2021 Nov 19. doi: 10.1007/s00204-021-03184-z. Online ahead of print.

ABSTRACT

Duchenne muscular dystrophy (DMD) afflicts 1 in 5000 newborn males, leading to progressive muscle weakening and the loss of ambulation between the ages of 8 and 12. Typically, DMD patients pass away from heart failure or respiratory failure. Currently, there is no cure, though exon-skipping therapy including eteplirsen (brand name Exondys 51), a synthetic antisense oligonucleotide designed to skip exon 51 of the dystrophin gene, is considered especially promising. Applicable to approximately 14% of DMD patients, a phosphorodiamidate morpholino oligomer (PMO) antisense oligonucleotide eteplirsen received accelerated approval by the US Food and Drug Administration (FDA) in 2016. Throughout clinical trials, eteplirsen has been well tolerated by patients with no serious drug-related adverse events. The most common events observed are balance disorder, vomiting, and skin rash. Despite its safety and promise of functional benefits, eteplirsen remains controversial due to its low production of dystrophin. In addition, unmodified PMOs have limited efficacy in the heart. To address these concerns of efficacy, eteplirsen has been conjugated to a proprietary cell-penetrating peptide; the conjugate is called SRP-5051. Compared to eteplirsen, SRP-5051 aims to better prompt exon-skipping and dystrophin production but may have greater toxicity concerns. This paper reviews and discusses the available information on the efficacy, safety, and tolerability data of eteplirsen and SRP-5051 from preclinical and clinical trials. Issues faced by eteplirsen and SRP-5051, including efficacy and safety, are identified. Lastly, the current state of eteplirsen and exon-skipping therapy in general as a strategy for the treatment of DMD are discussed.

PMID:34797383 | DOI:10.1007/s00204-021-03184-z

Evid Based Complement Alternat Med. 2021 Nov 9;2021:6645319. doi: 10.1155/2021/6645319. eCollection 2021.

ABSTRACT

OBJECTIVE: Nephritis or kidney inflammation is characterized as one of the most common renal disorders leading to serious damage to the kidneys. Nephritis, especially lupus nephritis (LN), has remained as the main cause of chronic renal failure which needs serious therapeutic approaches such as dialysis and kidney transplant. Heredity, infection, high blood pressure, inflammatory diseases such as lupus erythematosus and inflammatory bowel disease, and drug-related side effects are known as the main causes of the disease. According to Iranian traditional medicine (ITM), infectious diseases and fever are the main reasons of nephritis, which is called "Varam-e-Kolye" (VK).

RESULTS: There are various plant-based remedies recommended by ITM for the treatment of nephritis, as discussed herein, comparing with those available in the modern medicine. There is no definite cure for the treatment of nephritis, and immunosuppressive drugs such as corticosteroids and nonsteroidal anti-inflammatory drugs, antibiotics, diuretics, analgesics, and finally dialysis and kidney transplantation are usually used. Based on the efficacy of medicinal plants, jujube (Ziziphus jujuba), almond (Prunus amygdalus), pumpkin seeds (Cucurbita pepo), purslane (Portulaca oleracea), and fig (Ficus carica) were found to be effective for the treatment of kidney inflammation in ITM.

CONCLUSION: Considering the fact that there is no efficient strategy for the treatment of nephritis, use of herbal medicine, particularly based on the fruits or nuts that have been safely used for several years can be considered as a versatile supplement along with other therapeutic methods.

PMID:34795786 | PMC:PMC8595000 | DOI:10.1155/2021/6645319