Suitable Dose Research Articles

Effects of electron beam irradiation on protein oxidation and textural properties of shrimp (Litopenaeus vannamei) during refrigerated storage

Protein oxidation leads to changes in shrimp texture, which affects sensory profile and consumer acceptability. This study aimed to evaluate the impact of electron beam irradiation (EBI) on protein oxidation and textural properties of Litopenaeus vannamei during refrigerated storage. Results revealed that EBI treatment and storage increased the protein oxidation level of shrimps. Shrimps irradiated with ≥ 7 kGy exhibited remarkably higher (P < 0.05) reactive oxygen species, turbidity, and carbonyl contents, and remarkably lower (P < 0.05) Ca2+-ATPase activity, surface hydrophobicity, solubility, and total sulfhydryl contents compared to the control group (0 kGy) on the 7th day of storage. Shrimps irradiated with 3 and 5 kGy exhibited remarkably higher (P < 0.05) hardness, springiness, and chewiness compared to the control group (14.99 N, 1.26 mm, and 3.19 mJ). Collectively, suitable EBI doses of 3–5 kGy were recommended in shrimp preservation to inhibit texture softening by inducing moderate protein oxidation.

A review of small animal dosimetry techniques: image-guided and spatially fractionated therapy

Research in small animal radiotherapy is a crucial step in clinical translation of novel radiotherapy techniques, either delivered as stand-alone treatment or in combination with other treatments, such as chemotherapy and immunotherapy. In order to efficiently translate preclinical findings to the clinical setting, preclinical radiotherapy must replicate clinical therapy in terms of mode of delivery as well as dose delivery accuracy as closely as possible. In this review article, we focused on the description of dosimetry tools for radiotherapy of small animals delivered with kilovoltage x-ray beams on image-guided irradiators and in a spatially-fractionated manner by means of microbeam therapy. The specifics of dosimetry of kilovoltage x-ray beam deliveries with small, often sub-millimeter, beams are highlighted, and suitable dosimeters, phantoms, and dose measurement and calculation techniques are reviewed. Future directions for accurate real-time high spatial resolution dosimetry of small animal irradiations are also discussed.

Synergistic combination of Cinnamomum verum and Syzygium aromaticum treatment for cutaneous leishmaniasis and investigation of their molecular mechanism of action

ABSTRACT Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major. However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.

Organoruthenium 9E1 and APL Altered Collagen II263-272 Peptide as Therapy for Autoimmune Diseases

Therapy for autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS) is currently available in symptom management, pain-relieving, and mitigation of disease. Currently, prescribed drugs for patients with the disease work in specific mechanisms, regardless of failure to determine the most effective medication. We use a literature review to highlight two newly examined substances: organoruthenium 9E1 and APL altered collagen II263-272 peptide, and elaborate substances mentioned above' potential to be used in rheumatoid arthritis and MS therapy. Several studies show positive effects from 9E1 and altered CII263-272 peptides on experimented mice. Altered CII263-272 peptide can elicit Th cells to produce neurotrophic factors, decrease the body amount of pro-inflammatory T cells, increase the body amount of anti-inflammatory T cells, and alleviate collagen-induced arthritis symptoms. Meanwhile, 9E1 can inhibit Mst1 kinase effectively (IC50=45nM), giving consequences of decreasing Th1 cells' cytokines, increasing Th2 cells' cytokines, decreasing body amount's IgG1 and IgG2a, slowing down EAE and collagen-induced arthritis' manifestation, increasing IL-10 and IL-4-producing T cells. Organoruthenium and altered CII263-272 peptide possess positive and multiple effects as therapies for EAE and collagen-induced arthritis, hence potential to be prescribed to patients with rheumatoid arthritis and MS. This literature review suggests further research concerning 9E1 and altered CII263-272 peptide usage in the community to examine their effectivity, side effects, and suitable dose.&#x0D;

Planning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis C

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.

Foliar Application of Different Levels of Zinc and Boron on the Growth and Yield of Mungbean (Vigna radiate L.)

An experiment was conducted during Kharif-1 of 2022 at Bangladesh Institute of Nuclear Agriculture (BINA), Substation, Satkhira to know the effect of foliar application of micronutrients (zinc and boron) on the growth and yield of mungbean. There were three levels of zinc (Zn) (0.2%, 0.4%, 0.6%) and boron (B) (0.2%, 0.4%, 0.6%) along with a blanket dose of urea (35 kg ha-1, triple super phosphate (TSP) (80 kg ha-1), murite of potash (MoP) (40 kg ha-1) and Sulphur (60 kg ha-1). The growth and yield of mungbean was significantly affected by foliar application of different levels of Zn and B. Results revealed that foliar application of Zn at the rate of 0.6% and at the rate of B 0.6% along with recommended dose at 45 days after sowing increases the branches/plant, fresh weight (g), dry weight (g), chlorophyll content, flower/plant, pod/plant, seed/pod thereby increase seed yield. Therefore, the foliar spray of 0.6% Zn significantly increased and influenced 1000 seed weight (g), decreased days to flowering, increased number of seed/pod and yield ton/ha along with blanket dose of Urea, TSP, MoP, gypsum might be considered as suitable dose for mungbean production in southern region of Bangladesh.

Steroid treatment for COVID-19: Suitable dose and patients.

Steroid treatment for COVID-19: Suitable dose and patients.

Pharmacological Treatments and Therapeutic Drug Monitoring in Patients with Chronic Pain.

Pain is an unpleasant sensory and emotional experience that affects every aspect of a patient's life and which may be treated through different pharmacological and non-pharmacological approaches. Analgesics are the drugs most commonly used to treat pain, and in specific situations, the use of opioids may be considered with caution. These drugs, in fact, do not always induce optimal analgesia in patients, and several problems are associated with their use. The purpose of this narrative review is to describe the pharmacological approaches currently used for the management of chronic pain. We review several aspects, from the pain-scale-based methods currently available to assess the type and intensity of pain, to the most frequently administered drugs (non-narcotic analgesics and narcotic analgesics), whose pharmacological characteristics are briefly reported. Overall, we attempt to provide an overview of different pharmacological treatments while also illustrating the relevant guidelines and indications. We then report the strategies that may be used to reduce problems related to opioid use. Specifically, we focus our attention on therapeutic drug monitoring (TDM), a tool that could help clinicians select the most suitable drug and dose to be used for each patient. The actual potential of using TDM to optimize and personalize opioid-based pain treatments is finally discussed based on recent scientific reports.

Evaluating the effectiveness of a fixed little dose of radioactive iodine (I131) in treatment for Graves’ disease

Radioiodine (I131) therapy is a clinically established method for hyperthyroidism treatment. The most suitable dose for successful treatment is still controversial since it is affected by several factors. Thus, there are two techniques for proper dose adjustment; Fixed and calculated.This study aims to evaluate the response difference of hyperthyroidism to a low fixed dose of 5 mCi (185 MBq) in comparison with other fixed doses of 10 mCi and 15 mCi (370 and 555 MBq) radioactive iodine treatment protocols. It also aims to raise the possibility of euthyroid state after successful ablation with such a low fixed dose rather than hypothyroid results and long-life replacement therapy.A prospective study of 100 patients were clinically and scintigraphically diagnosed with Graves' disease (GD) from the endocrinology department at King Faisal Medical Complex. The kind and size of the patient's thyroid were determined before treatment and then randomized into three groups, based on the administrated radioactive iodine dose, (5 mCi, Group I), (10 mCi, Group II) and (15 mCi, Group III). The thyroid function tests were performed after 3 and 6 months, as a follow-up, for the assessment of the outcome.Similar responses for fixed doses of 5, 10 and 15 mCi were determined, with no significant difference between the three study groups. Successful ablation was achieved in 23 (71.9%), 27 (84.4%) and 22 (71.0%) patients in the 5, 10, 15 mCi groups respectively without a significant difference between the groups with p-value of 0.695. Moreover, all considered related factors to the outcomes show no effect except the thyroid size with a p-value <0.001. The baseline size of the thyroid gland was significantly smaller in the Successful ablation group and the Euthyroidism group as compared to the Hyperthyroidism group (51.36 ± 4.32 and 53.73 ± 5.19 vs. 70.54 ± 8.70; p < 0.001).Fixed little doses of 5, 10 or 15 mCi of I131 show comparable remission rates. These outcomes were not affected by any factor related to the thyroid except thyroid size. Larger thyroid glands have less chance of remission. So, we envisage that a 5 mCi of radioactive iodine dose is recommended as a routine treatment for patients diagnosed with GD.

Study of different doses of zinc oxide nanoparticles by intraperitoneal and gavage methods on testicular tissue in Wistar rats: An experimental study.

Zinc oxide nanoparticles (ZnO-NPS) are widely used inhuman life; however, they do have side effects on human health. This study aimed to evaluatethedifferent doses of ZnO-NPS on testicular tissue. 35 male Wistar rats(10-12 wk, 220 20gr) were divided into 7 groups of 5, including the control group (gavaged distilled water daily), sham group (received intraperitoneal doses of distilled water twice a week). The group receivedintraperitoneal ZnO-NPS (25, 50, and 100 mg/kg body weight, twice a week), and gavage (150 and 200 mg/kg body weight daily). All stages of the test were performed in 4 wk then serum testosterone and tissue malondialdehyde, and ferric reducing antioxidant power levels were measured, also testes histopathological evaluation was performed. Our results showed that a reduced cell population of spermatozoa was observed in the group that received 25 mg/kg ZnO-NPS, while a reduced cell population of spermatozoa, edema, hyperemia, and vacuolar degeneration were observed in the group that received 50 and 100 mg/kg ZnO-NPS. The maximum amount of lesions were observed in the dose of 200 mg/kg. The highest amount of ferric reducing antioxidant power and testosterone levels were observed in the control group. Also, a 100 mg/kg intraperitoneal dose of ZnO-NPS and 150 mg/kg oral dose of ZnO-NPS were suitable doses to create a model of male genital lesions. Nanoparticles are harmful factors for the reproductive system and consequently affect infertility, which requires the toxicity of the concentration of these nanoparticles to be evaluated and controlled.

Understanding Statin-Roxadustat Drug-Drug-Disease Interaction Using Physiologically Based Pharmacokinetic Modeling.

A different drug-drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HV), depending on the interplay between drug-drug and disease (drug-drug-disease interaction, DDDI). Physiologically based pharmacokinetic (PBPK) modelling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modelling in severe CKD population is still low when non-renal pathways are involved. More mechanistic virtual disease population and robust validation cases are needed. To this end, we aimed to: 1) understand the implications of severe CKD on statins (atorvastatin, simvastatin, and rosuvastatin) PK and DDI; and 2) predict untested clinical scenarios of statin-roxadustat DDI risks in patients to guide suitable dose regimens. A novel virtual severe CKD population was developed incorporating the disease effect on both renal and non-renal pathways. Drug and disease PBPK models underwent a four-way validation. The verified PBPK models successfully predicted the altered PK in patients for substrates and inhibitors and recovered the observed statin-rifampicin DDIs in patients and the statin-roxadustat DDIs in HV within 1.25- and 2-fold error. Further sensitivity analysis revealed that the severe CKD disease effect on statins PK is mainly mediated by hepatic BCRP for rosuvastatin and OATP1B1/3 for atorvastatin. The magnitude of statin-roxadustat DDI in severe CKD patients was predicted to be similar to that in HV. PBPK-guided suitable dose regimens were identified to minimize the risk of side effects or therapeutic failure of statins when co-administered with roxadustat.

Adenovirus vector produced Zika virus-like particles induce a long-lived neutralising antibody response in mice

Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed the immunogenicity of these particles in mice. The ZIKV-VLPs were morphologically similar to ZIKV by electron microscopy and were recognized by anti-Flavivirus neutralising antibodies. We observed that a single dose of unadjuvanted ZIKV-VLPs, or inactivated ZIKV, generated an immune response that lasted over 6 months, but did not neutralize ZIKV infection of cells in vitro. However, when we co-administered the ZIKV VLPs with either Aluminium hydroxide (Alhydrogel®; Alum), AddaVax or Pam2Cys we observed that Alum was the most effective in a single dose regime, since it not only produced antibodies that neutralized the virus, but also generated a greater number of antigen-specific memory B cells. We additionally observed that the generation of the neutralising antibodies persisted for up to 6 months. Our results suggest that a single dose ZIKV VLPs could be a suitable single dose vaccine candidate for use in outbreak settings.

Distance‐dependent attraction of the generalist aphid parasitoid Aphidius colemani towards synthetic volatile organic compounds under greenhouse conditions

AbstractManipulation of insect foraging may provide the basis for effective insect pest control strategies. Recent laboratory and small‐scale greenhouse experiments have shown that a blend of styrene and benzaldehyde is attractive to some Aphidius parasitoids, making it a good candidate for attracting and retaining these natural enemies in cropping systems. However, an appropriate dispenser type and appropriate dose for field application and its attraction range have yet to be identified. In this study, we performed experiments to determine an appropriate dispenser type – Omnilure® vs. low‐density polyethylene (LDPE) bags – and the most suitable dose to attract Aphidius colemani Viereck (Hymenoptera: Braconidae) under commercial greenhouse conditions and to determine the maximum distance of attraction. A mixture of 10 mg styrene and 100 μg benzaldehyde was the most attractive dose for A. colemani when provided by the dispensers under greenhouse conditions. The highest percentage of parasitoids was attracted when insects were released at a distance of 0.5 m from the Omnilure dispensers. Nevertheless, compared to the solvent control the blend of styrene and benzaldehyde remained attractive over a distance of up to 5 m. The potential application of these results in novel augmentation biocontrol strategies is discussed.

Preparation and Evaluation of Repaglinide Loaded Liposomes by Ether Injection Method

Repaglinide is a commonly used antidiabetic drug to treat type 2 diabetes mellitus. However, it does not always support a suitable dose regimen due to its low bioavailability and half-life. The purpose of this study was to develop and analyze repaglinide loaded control release liposomes to provide suitable dosage form to treat diabetes. Repaglinide loaded liposomes were prepared by modified ether injection method. According to the USP-II paddle method, in vitro dissolution studies of liposomes were performed for 8 hours in phosphate buffer (pH 7.4). The stability study was executed according to ICH guidelines under three different environmental conditions for 14 days. Additionally, the presence and size of liposomal vesicles was confirmed by microscopic observation. The formulations containing phosphatidylcholine and cholesterol at a molar ratio of 1:0.4 revealed the highest drug entrapment efficiency of 73.1% with an optimum stirring rate of 300 RPM. The pegylated liposomes (PEG400/1500) prolonged the drug loading capacity for the formulations compared to non-pegylated liposomes. On the contrary, the addition of nigella oil caused a decrease in entrapment efficiencies of the liposomes. Most of the formulations followed zero order kinetic model and supper class II release mechanism. In vitro dissolution showed controlled release pattern of the liposomes and maximum drug release after 8 hours was 92.64%. Additionally, all the liposomal formulations were found to be more stable at refrigeration temperature (5 ± 2ºC) where pegylated liposomes were most stable over 14 days at three different environmental conditions. Visual observation under an optical microscope, the vesicular structure of liposomes was confirmed. Dhaka Univ. J. Pharm. Sci. 22(1): 89-96, 2023 (June)

The Effects of Fly Ash and Cow Manure on Water Spinach Grown on An Ultisol of Lampung, Indonesia

Fly ash is the residue of coal combustion that can potentially be an ameliorant. Unfortunately, its use is limited by government regulations that are classified as hazardous and toxic materials. This study examines the effectiveness of fly ash and cow manure as an ameliorant for Ultisols. The experiment was carried out by two factors, i.e., the dose of fly ash, namely 0, 50, 100, and 150 t/ha, and the quantity of cow manure, i.e., 10, 20, and 30 t/ha. The results show that fly ash and cow manure could be ameliorants for low-pH soils such as Ultisols. The suitable dose of fly ash and cow manure as ameliorants in this study are 50 t/ha and 20 t/ha, respectively. Increasing the amount of fly ash caused a decrease in the growth of water spinach, plant height, number of leaves, fresh plant weight, root length, and dry weight of the root. In addition, fly ash increased pH 6.66-7.30, total P 31.74-52.21 mg/100 g, and total K 16.19-25.75 mg/100 g.

Probiotics for Preventing Necrotizing Enterocolitis: A Meta-Analysis with Trial Sequential Analysis

What is Known and Objective. The role of probiotics, especially the different genera of probiotics, in managing necrotizing enterocolitis (NEC) is controversial. Thus, we performed a meta-analysis with trial sequential analysis (TSA) to determine the efficacy and safety of probiotics for preventing NEC. Methods. Medline, Embase, CENTRAL, WorldCat, TROVE, DART-Europe, and CBM were searched from inception to May 2022. Two investigators independently screened the literature, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4, and TSA was conducted using TSA 0.9 beta. Results and Discussion. Fifty-five studies involving 12897 newborns were eligible. The use of probiotics for preventing NEC reduced the incidence of NEC (RR 0.48, 95% CI 0.41 to 0.57, and P &lt; 0.05) and sepsis (RR 0.77, 95% CI 0.64 to 0.94, and P &lt; 0.05), the risk of mortality (RR 0.69, 95% CI 0.58 to 0.84, and P &lt; 0.05), and shortened the average days of hospitalization (MD −3.12, 95% CI −4.98 to −1.26, and P &lt; 0.05). However, subgroup analysis revealed that different genera of probiotics gave rise to different outcomes. In addition, TSA indicated that the cumulative z-curve crossed the traditional and trial sequential monitoring boundaries for benefit, providing firm evidence that multiple strains and Lactobacillus species of probiotics decreased the incidence of NEC. However, the current evidence was inconclusive for Bifidobacterium and Saccharomyces species. What is New and Conclusions. Probiotics are effective in preventing NEC and sepsis and could provide added benefits, including decreasing mortality and the number of days of hospitalization. However, considering the heterogeneity of probiotics regimens and the risk of selective reporting of RCTs, more high-quality clinical trials targeting different genera of probiotics with suitable doses and timing to prophylactic use of probiotics are needed to avoid overestimating the role of probiotics in preterm infants.

Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.

Regulation of semen quality by fatty acids in diets, extender, and semen.

Fatty acids (FAs) are classified into different types according to the degree of hydrocarbon chain saturation, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and omega-6 polyunsaturated fatty acids (omega-6 PUFAs), which play an important role in maintaining semen quality. This review focuses on the regulation of FAs in semen, diet and extender on semen quality, and expounds its effects on sperm motility, plasma membrane integrity, DNA integrity, hormone content, and antioxidant capacity. It can be concluded that there are species differences in the FAs profile and requirements in sperm, and their ability to regulate semen quality is also affected by the addition methods or dosages. Future research directions should focus on analyzing the FAs profiles of different species or different periods of the same species and exploring suitable addition methods, doses and mechanism of regulating semen quality.

Evaluation of Serum Ferritin, Creatinine and Liver Enzymes in Patients with ß- thalassemia After Administration of Deferasirox

Background: Iron overload is the most common complication of ß- thalassemia thatcauses morbidity and mortality in children so chelating drugs are essentials forpreventing such complication. Oral deferasirox has a good safety and tolerance tomaintain ferritin level in non-toxic levels that affect heart and liver. Patients andmethods: A cohort retro - prospective study of eighty five patients 45 male(53%), 40female (47%), age from 2-18 years old, with ß-thalassemia who receiving deferasiroxin thalassemia center in Kirkuk city north of Iraq from the first of March to the end ofOctober 2016; that assessed by interview questionnaire, previous documents in thecenter and laboratory investigations for serum creatinine, serum ferritin and liverenzymes. Results: Adverse effects were shown in eight patients (9.4%), each of two(25%) had abdominal pain, increase appetite, and hair loss consecutively, allergy andnervousness in each one patient(12.5%) serum ferritin was decreased below thebaseline in 47 (55.3%), serum creatinine was elevated above the baseline in 22(25.8%) within normal levels, Elevated serum alanine transferase in 16 (18.8%), totalserum bilirubin was elevated in 14(16.6%) of all children; while serum aspartatetransferase elevated in 22(25.8%) of the normal eventually serum alkalinephosphatase was elevated in 22(25.8%). Conclusion: Deferasirox is well tolerated asan iron chelating with suitable dose and long duration has less adverse effects and canbe adjusted by dose modification.

Abstract CT250: An open-label, phase 1a/b study of AB248, a CD8+ selective IL-2 mutein fusion protein, alone or in combination with pembrolizumab in patients with advanced solid tumors

Abstract Background: High-dose interleukin-2 (HD IL-2) induces durable clinical responses in a subset of patients with melanoma and RCC, but severe toxicity limits its therapeutic utility. Early clinical data from several not-α IL-2Rβγ agonists suggest better tolerability but lower objective response rates compared to historical HD IL-2 data.1-2 In patients, these not-α IL-2s demonstrate a profound NK cell bias, while retaining activity on Tregs, and exhibiting limited CD8+ T cell expansion.3-5AB248 is a CD8+ selective IL-2 that demonstrates more than 500-fold selectivity for CD8+ T cells over other immune cell types. AB248 has demonstrated a highly differentiated preclinical profile, with compelling anti-tumor activity and less toxicity when given alone and in combination with anti-PD1 in multiple murine tumor models. These data suggest that AB248 may have an improved therapeutic index compared to broad-acting IL-2Rβγ agonists by increasing CD8+ T cell expansion and activation, avoiding NK cell-driven toxicity and avoiding Treg-mediated immunosuppression. Here we introduce the first-in-human study which aims to investigate AB248 when administered alone and in combination with pembrolizumab in subjects with advanced solid tumors who failed prior standard of care therapies. Methods: This open-label phase 1a/b study consisting of a dose escalation and expansion phase aims to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of AB248 alone or in combination with pembrolizumab in subjects with locally advanced/metastatic tumors, including melanoma, renal cell carcinoma, NSCLC and SCCHN, who failed prior therapies, including prior anti-PD(L)1, as well as in first-line SCCHN during the expansion phase. Key eligibility criteria include age ≥18 years, ECOG ≤1, measurable disease per RECIST v1.1, adequate end-organ function, and no autoimmune disease. The dose escalation phase will follow the Bayesian Optimal Interval (BOIN) design and enroll subjects at multiple dose levels and schedules for the AB248 monotherapy and pembrolizumab combination portion. Upon identifying suitable dose and schedule based on the totality of cumulative data including safety, PK, PD and preliminary efficacy, additional subjects will be enrolled in indication specific cohorts in the expansion phase according to the Simon 2-stage design. The primary objectives for this study are to assess the safety and tolerability of AB248 alone or in combination with pembrolizumab. Secondary objectives include assessing the PK, PD changes, immunogenicity, and antitumor activity. Exploratory objectives include evaluating the potential response-predictive and/or associated changes in immune cells, blood, and tissue biomarkers. Tumor assessments will be performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter. Adverse events will be assessed by CTCAE v5.0. The study is currently open for enrollment in the dose escalation phase at multiple sites in the US. Citation Format: Elizabeth I. Buchbinder, David R. Spigel, Costantine Albany, Michael Chisamore, Kelly D. Moynihan, Xiaohan Liu, Christopher DelNagro, Matt Axt, Andrea Pirzkall. An open-label, phase 1a/b study of AB248, a CD8+ selective IL-2 mutein fusion protein, alone or in combination with pembrolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT250.