High Doses Of Drug Research Articles

Advanced treatment-resistant ovarian germ cell tumor (yolk sac tumor) with successful fertility realization 20 years after combined treatment: a case report

Background. Yolk sac tumors (YST) are classified as rare malignant germ cell tumors of the ovaries, most commonly found in young patients interested in preserving fertility. YST is characterized by large size, predominantly unilateral involvement, and increased production of alpha-fetoprotein, which can be used as an important diagnostic criterion for this condition. Among all germ cell tumors, YST has the least favorable prognosis. The primary goals of YST treatment are not only to improve prognosis and quality of life but also to enable the patient to fulfill her reproductive plans in the future.Description of the clinical case. We present a clinical case of an aggressive course of yolk sac tumor in the ovary of a 15-year-old girl, requiring multiple surgeries, repeated courses of high-dose drug therapy, and bone marrow transplantation.Conclusion. This is a rare case of YST with successful preservation of reproductive function due to modern medical technologies despite aggressive treatment.

Fast onset of thrombolytic effect of efficiently inhalable spray-dried rivaroxaban powder formulations

Pulmonary embolism is a critical medical condition and can lead to cardiovascular arrest or death if left untreated. Pulmonary delivery of an anti-coagulant therapeutic could provide a locally limited and efficient therapy, moreover combined with a potentially fast onset of the therapeutic effect that is demanded in emergency situations. Rivaroxaban (riva) was formulated as an inhalable dry powder that can be administered directly to the lungs in order to reach high local drug doses. Particles obtained spray drying dichloromethane-methanol mixtures yielded an aerodynamic diameter of about or smaller than 5 µm and were found to reach an emitted fine particle fraction (FPFEF) of at least 60 %. Pulmonary administration to rats using a dry powder insufflator revealed a nearly immediate therapeutic onset confirmed by the anticoagulant effects after 5 min in the plasma followed by a plateau over the next 4 h. Such rivaroxaban particles were further formulated in binary blends using different lactose carriers (Inhalac® 70/251/400). These interactive blends resulted in high emitted fractions of at least 87 %, and furthermore, the highest fine particle fraction − total dose (FPFTD) (60 %) of all tested formulations was achieved by using Inhalac® 400 as a carrier. The data strongly suggest a significant therapeutic potential of a rivaroxaban dry powder formulation, combining fast onset and a plateau of plasma concentrations turning it into a potential first aid therapeutic.

Gegen Qinlian Decoction Modulates Atherosclerosis and Lipid Metabolism Through Cellular Interplay and Signaling Pathways.

The objective of this study is to investigate Gegen Qinlian decoction (GQD) effects on lipid metabolism and explore its mechanism for preventing and treating atherosclerosis. An atherosclerotic rat model was established, and after an 8-week high-fat diet, atherosclerosis and non-alcoholic fatty liver disease were assessed. Subsequently, GQD was administered at low and high doses. Histopathological aortic wall changes, hepatic lipid deposition, and blood lipid changes were evaluated. ELISA indicated the influence of TNF-α and IL-13, and Western blotting revealed MerTK, ABCA1, and LXR-α expression. A foam macrophage model was established, and Cell activity was detected by the MTT method. ELISA indicated the influence of PPAR-γ. The expression of ABCA1, ABCA7, ABCG1, GAS6, MerTK, SCARB1, LXR- α and LXR-β mRNA were detected by qPCR. and Western blotting revealed MerTK and LXR-α expression. The impact of drug-containing serum of GQD on efferocytosis-related factors was studied. GQD improved atherosclerosis and non-alcoholic fatty liver disease and reduced serum low-density lipoprotein levels in the high-dose group. The high- and low-dose groups showed upregulated ABCA1, MerTK, and LXR-α expression in blood vessels and the liver, respectively. GQD decreased serum TNF-α and increased IL-13 levels. PPAR-γ expression was elevated in the high-, and low-dose groups. In the high-and low-dose groups, ABCA7, GAS6, SCARB1, and LXR-α, ABCA1 and MerTK, and ABCG1 gene expression were upregulated, respectively. Both low- and high-dose serum-containing drugs promoted LXR-β gene expression, and LXR-α protein expression was improved in the high-dose group. GQD improves rat atherosclerosis and hepatic lipid metabolism by regulating PPAR-γ, LXR-α, LXR-β, ABCA1, ABCA7, and ABCG1 expression and augmenting cellular intercalation through the GAS6/TAM pathway.

Evaluation of Hesperidin-Zinc Complex as a Novel Therapeutic Agent for Depression Treatment in Rats

Introduction: The complex contains hesperidin and zinc. The zinc is essential micronutrient that is important for human metabolism and catalyzes over 100 enzymes. It can be used to treat Wilson disease, decreased immunity, acute and chronic diarrhea. The hesperidin is a bioflavonoid found in many citrus plants. It has numerous activities like antioxidant, antibacterial, antimicrobial, anti-inflammatory, used to treat inflammation, Hypotension, varicose veins, venous ulcer, oxidative stress. There is no scientific evidence to support the claim that the complex of hesperidin and zinc have antidepressant properties even though zinc and hesperidin both separately have been linked to antidepressant activity in the literature. Objectives: The aim of this research is to find out whether complex of hesperidin and zinc can prevent reserpine induced depression. Methods: Wistar rats were used in this study after acclimatization. The induction group will be induced with reserpine to produce the depression in rats. The experiment included various treatment group of high and low dose of the test drug. Rats were used for the assessments, based on behavioral parameter like tail suspension test (TST), forced swimming test (FST), and elevated plus maze test then histopathology of hippocampus, cortical and substantia nigra region has been analysed, and along with measuring the BDNF levels. Results: On reserpine induced depression, complex of Hesperidin and zinc at low dose (100 mg/kg) shows negligible improvement in depressed behavior, when compare with standard fluoxetine (10 mg/kg). On the other hand, high dose (200 mg/kg) of the complex shows greater improvement also showed normal morphology in all 3 regions of the brain and showed increased level of BDNF in brain compared to low dose (100 mg/kg). Conclusions: Hesperidin-zinc complex was discovered to be a successful antidepressant drug, according to the study's findings. According to the findings, however a high dose of complex is more effective at treating reserpine induced depression than a low dose of complex.

Evaluation of MMP-9 enzyme in drug-induced suicide cases admitted to the emergency room

ObjectiveThis study investigates MMP-9 enzyme levels in patients who attempted suicide by taking high doses of drugs, considering their sociodemographic characteristics. MethodsThe study included 45 patients who attempted suicide by high-dose drug intake admitted to the emergency room and 45 healthy volunteers with no neuropsychiatric disorders. Blood samples were collected to measure MMP-9 levels, and informed consent was obtained. The samples were centrifuged and analyzed using the ELISA method, with results statistically compared. ResultsFindings indicate that being single and a student significantly increased suicide tendencies (p = 0.002 and p = 0.001, respectively). Psychiatric disorders were the most common cause at 40.0%, followed by antidepressants (55.6%), analgesics (20.0%), and antidiabetics (8.9%) as the most used drugs for suicide. MMP-9 levels were significantly higher in patients who attempted suicide compared to controls (83.74 (±7.14) ng/mL vs. 54.97 (±12.27) ng/mL, p = 0.001). Additionally, MMP-9 levels were higher in single patients compared to married or divorced individuals (p = 0.008). MMP-9 levels were lower in patients with psychiatric disorders, recent psychiatric services, family history of psychiatric disorders, and previous suicide attempts (p = 0.014, p = 0.046, p = 0.035, p = 0.034). ConclusionsThis study shows MMP-9 enzyme can be a potential biomarker for drug-induced suicide attempts, emphasizing the importance of evaluating MMP-9 levels to assess suicide risk and develop prevention strategies.

Single-Step Extrusion Process for Formulation Development of Self-Emulsifying Granules for Oral Delivery of a BCS Class IV Drug.

This study aimed to develop and optimize formulations containinga BCS Class IV drug by improving its solubility and permeability. Herein development of self-emulsifying solid lipid matrices was investigated as carrier systems for a BCS Class IV model drug. Self-emulsifying drug delivery systems (SEDDS) have been extensively investigated for formulating drugs with poor water solubility. However, manufacturing SEDDS is challenging. These systems usually have low drug-loading capacities, and the incorporated drugs tend to recrystallize during storage, which severely impacts the storage stability in vitro and performance in vivo. Moreover, they require greater amounts (>80%) of lipid carriers, cosolvents, surfactants, and other excipients to keep them from recrystallizing. This in turn is again challenging for high-dose drugs as it affects the size of the final drug product (tablets and capsules). Also, the final liquid nature of the formulation affects the handling and processability of the formulation, which poses challenges during the manufacturing and packaging steps. In this work, we have studied the feasibility of a single-step extrusion process to formulate and optimize solid self-emulsifying granules with a relatively higher drug loading of Ritonavir (RTV), a BCS Class IV drug. Further, we have compared the performance of using these granules as the feedstock for direct powder extrusion-based 3D printing as opposed to the use of physical blends. The stability and solubility-permeability advantage of these granules was also evaluated where SEDDS showed about 27 and 20 fold increase in apparent solublity and permeability compared to bulk drug, respectively. Combining the capabilities of HME to form drug-loaded homogeneous granules as a continuous process along with application of direct printing extruiosn (DPE) 3D printing improves the drug delivery prospects for such candidates.

12214 Metastatic Functional Thyroid Carcinoma As An Unusual Cause Of Hyperthyroidism

Abstract Disclosure: S. Jimenez Salazar: None. N. Aristizabal Henao: None. C. Aguilar Londoño: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Differentiated thyroid carcinoma (DTC) represents the most prevalent endocrine neoplasm. Less than 10% present distant metastases, with the lung (50%), and skeleton (25%) being the most frequently affected sites. The location of bone metastases predominates in the spine and pelvis; usually as osteolytic lesions, being more frequent in follicular thyroid cancer (FTC) (7-28%) than in patients with papillary thyroid cancer (PTC) (1.4-7%). In rare cases this metastasis can be functional and trigger a thyrotoxicosis syndrome with or without recombinant human TSH injections prior to therapy with 131-I. Clinical case: 59-year-old woman with a history of bone metastatic follicular thyroid cancer (FTC) presented with 1 month of palpitations, 4 kg weight loss, non-dysenteric diarrhea and progressive dyspnea. Her FTC had been diagnosed 8 years prior her consultation. In that time iodine refractoriness was considered due to the progression of bone lesions, and Sorafenib 800 mg per day was initiated, which was not tolerated due to severe dermatological manifestations, and the patient decided not to continue with TKI therapy. Since then, she has been treated with zoledronic acid and local radiotherapy as part of palliative care. On physical examination, she was tachycardic (150 bpm), and hypertensive (BP 160/100 mmHg). A suppressed TSH (<0.01 uUI/mL, n: 0.4-4 uUI/mL) with elevation of thyroid hormones (free T4 3.99 ng/dL, n: 0.8-2 ng/dL and total T3 480 ng/dL, n: 45-140 ng/dL) was documented, associated with a patient who had required a dose adjustment of levothyroxine from 700 mcg to 350 mcg weekly 2 months prior to admission. Additionally, she had a significantly elevated thyroglobulin (>5000 ng/mL, n: 0.1-64.1 ng/mL) with undetectable antithyroglobulin antibodies (1.09 UI/mL, n: 0-4.11 UI/mL). Considering the history of total thyroidectomy and the high tumor burden, secondary thyrotoxicosis due to functioning bone metastases of DTC was considered. Levothyroxine was discontinued, and propranolol was initiated for the control of adrenergic symptoms, along with methimazole, cholestyramine, and systemic steroids to control thyroid hormone production. 3 days after therapy adjustment dyspnea, palpitations, and thyroid function tests improved significantly (free T4 1.43 ng/dL, n: 0.8-2 ng/dL and total T3 178 ng/dL, n: 45-140 ng/dL). A new administration of therapy with 131-I 200 mCi was indicated. Antithyroid therapy and beta-blockers were continued with sustained biochemical control. Conclusion: Functional bone metastases of FTC can lead to high morbidity and mortality. Treatment consists of surgical cytoreduction of any large accessible metastatic lesion, therapy with 131-I, and high-dose antithyroid drugs to control hyperthyroidism. It is important to avoid the use of recombinant human TSH due to the risk of secondary thyrotoxicosis following its administration. Presentation: 6/2/2024

Liposome-Assisted Drug Delivery in the Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the nervous system that leads to neurological dysfunctions and severe disabilities. It is worth noting that conventional pharmacotherapy is poorly selective and causes toxicity problems and several systemic side effects. Thus, there is a need to develop new approaches to this medical challenge. The use of nanocarriers for drug delivery represents a good strategy to overcome several issues such as high therapeutic drug doses with side effects, such as diarrhea, nausea, and abdominal pain, and drug degradation processes; in addition, nanocarriers can provide controlled and targeted drug release. This review describes the application of liposomes for the delivery of pharmaceutical actives to target MS. Firstly, MS is explained. Then, liposomes are described along with their preparation, characterization, and stability. The literature about the use of liposomes for the treatment of MS is then analyzed.

Dissolution profiles of high-dose salt-form drugs in bicarbonate buffer and phosphate buffer

The purpose of the present study was to compare the dissolution profiles of high-dose salt-form drugs in bicarbonate buffer (BCB) and phosphate buffer (PPB) focusing on the pH changes in the bulk phase. The pH titration curves of BCB and PPB (pH 6.5, buffer capacity (β) = 4.4 mmol/L/pH unit) were first theoretically calculated and experimentally validated. For dissolution tests, six drug salts with an acid counterion, one drug salt with a weak base counterion, and one free acid drug were employed (125 to 800 mg clinical dose). The dose/fluid volume ratio (Dose/FV) was aligned with the clinical condition. In the pH titration study, the pH value decreased below pH 6.0 by adding HCl > 2.8 mmol/L (BCB) or > 1.6 mmol/L (PPB) and increased above pH 7.0 by adding NaOH > 2.0 mmol/L (BCB) or > 2.4 mmol/L (PPB). In the dissolution test, even though the initial pH and β values were the same, the pH value at 4 h was lower in PPB than in BCB in all cases. For the drug salts with an acid counterion, the area under the dissolution curve was 1.2 to 2.6-fold lower in BCB than in PPB. A marked precipitation process was observed in BCB, but less pronounced or absent in PPB. The results of this study suggest the use of BCB and a clinically equivalent Dose/FV may be valuable in predicting the oral absorption of high-dose drug salts.

A call for compassionate opioid overdose response

High dose and long-acting opioid overdose reversal drugs can precipitate withdrawal in people who are opioid dependent. Products recently brought to market for community use in the United States (US) have drawn international concern because of their increased risk of withdrawal. At the March 18–19, 2024, Compassionate Overdose Response Summit & Naloxone Dosing Meeting, a panel of harm reduction experts issued the following call to action: 1) people who use drugs should be directly involved in decisions regarding the research, development, selection, and distribution of opioid overdose reversal products; 2) regulatory agencies and pharmaceutical manufacturers should carefully consider and communicate the risk and duration of withdrawal associated with higher dose and longer-acting opioid antagonists; 3) take-home naloxone kits should include at least two doses of an intramuscular (IM) product containing 0.4 mg or an intranasal (IN) product containing ≤4 mg; 4) At this time, high dose and long-acting opioid antagonists have no use in acute opioid overdose response; and, 5) overdose response educational materials, instructions on overdose response, and training should emphasize the restoration of breathing, avoiding withdrawal, and compassionate post-overdose support and care. High dose and long-acting opioid overdose reversal drugs were approved without testing for withdrawal and are often aggressively marketed despite decades of evidence from naloxone distribution programs worldwide that the ideal dose of naloxone is one that restores breathing without inducing withdrawal. Government agencies should direct resources to harm reduction programs to make standard dose take-home naloxone products widely available among people who use drugs. Lay bystanders, people who use drugs, their families, and professional first responders can learn and apply a compassionate approach to opioid overdose response.

Intranasal Administration of Bedaquiline-Loaded Fucosylated Liposomes Provides Anti-Tubercular Activity while Reducing the Potential for Systemic Side Effects.

Liposomal formulations of antibiotics for inhalation offer the potential for the delivery of high drug doses, controlled drug release kinetics in the lung, and an excellent safety profile. In this study, we evaluated the in vivo performance of a liposomal formulation for the poorly soluble, antituberculosis agent, bedaquiline. Bedaquiline was encapsulated within monodisperse liposomes of ∼70 nm at a relatively high drug concentration (∼3.6 mg/mL). Formulations with or without fucose residues, which bind to C-type lectin receptors and mediate a preferential binding to macrophage mannose receptor, were prepared, and efficacy was assessed in an in vivo C3HeB/FeJ mouse model of tuberculosis infection (H37Rv strain). Seven intranasal instillations of 5 mg/kg bedaquiline formulations administered every second day resulted in a significant reduction in lung burden (∼0.4-0.6 Δlog10 CFU), although no differences between fucosylated and nonfucosylated formulations were observed. A pharmacokinetic study in healthy, noninfected Balb/c mice demonstrated that intranasal administration of a single dose of 2.5 mg/kg bedaquiline liposomal formulation (fucosylated) improved the lung bioavailability 6-fold compared to intravenous administration of the same formulation at the same dose. Importantly, intranasal administration reduced systemic concentrations of the primary metabolite, N-desmethyl-bedaquiline (M2), compared with both intravenous and oral administration. This is a clinically relevant finding as the M2 metabolite is associated with a higher risk of QT-prolongation in predisposed patients. The results clearly demonstrate that a bedaquiline liposomal inhalation suspension may show enhanced antitubercular activity in the lung while reducing systemic side effects, thus meriting further nonclinical investigation.

Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

Enhancing capture efficiency of drug-carrier particles in the carotid sinus by utilizing a combination of magnetic fields: A numerical approach

Magnetic drug targeting is a relatively new method to treat vascular occlusion in different body parts. However, the effectiveness of this method can be affected due to the severity and location of the occlusion. This can lead to the injection of high dosages of drugs, which can cause serious side effects due to the deposition of drugs in unwanted parts. To mitigate these effects, this study investigates the potential of a guiding magnetic field in enhancing drug absorption for vascular occlusion treatment. The method relies on guiding magnetic nanoparticles (NPs) loaded with drugs toward the occlusion site using two external magnetic fields. Blood flow was modeled as non-Newtonian, considering shear-rate-dependent viscosity and unsteady at the inlet. To test this idea, a computational fluid dynamic (CFD) coupled with a discrete phase model (DPM) approach has been employed to simulate drug delivery in three-vessel structures with varying degrees of occlusion (45 %, 60 %, and 90 %). To avoid the escape of drug carriers, a secondary magnetic field was applied at the bifurcation point to direct the NPs to the site of blockage where the primary magnetic field acts. Then, the states with or without a guiding source at the bifurcation site are compared based on the capture efficiency of each structure. The simulation demonstrated a significant increase in NP capture at the target site, ranging from 2 % to 15 %, depending on the NP size. However, the severity of occlusion substantially impacted the secondary magnetic field's effectiveness. In the 90 % occlusion scenario, the method's efficiency decreased significantly from 26 % to 16 % for NP sizes exceeding 1.5μm. This study highlights the potential of guiding magnetic fields in improving drug delivery to target sites in vascular occlusion.

Engineered nanoparticles potentials in male reproduction.

The escalating prevalence of fertility problems in the aging population necessitates a comprehensive exploration of contributing factors, extending beyond environmental concerns, work-related stress, and unhealthy lifestyles. Among these, the rising incidence of testicular disorders emerges as a pivotal determinant of fertility issues. Current treatment challenges are underscored by the limitations of high-dose and frequent drug administration, coupled with substantial side effects and irreversible trauma inflicted by surgical interventions on testicular tissue. The formidable barrier posed by the blood-testis barrier compounds the complexities of treating testicular diseases, presenting a significant therapeutic obstacle. The advent of nanocarriers, with their distinctive attributes, holds promise in overcoming this impediment. These nanocarriers exhibit exceptional biocompatibility, and membrane penetration capabilities, and can strategically target the blood-testis barrier through surface ligand modification, thereby augmenting drug bioavailability and enhancing therapeutic efficacy. This review concentrates on the transformative potential of nanocarriers in the delivery of therapeutic agents to testicular tissue. By summarizing key applications, we illuminate the strides made in utilizing nanocarriers as a novel avenue to effectively treat testicular diseases. Nanocarriers are critical in delivering therapeutic agents to testicular tissue.

Magnetically controlled transdermal delivery of gemcitabine via xanthan gum-coated magnetic nanoparticles embedded in gellan gum cryogel

Chemotherapy is a commonly used treatment for breast cancer, but it often causes significant side effects due to the high drug dosage required for injection or infusion administration. Transdermal drug delivery offers a non-invasive and controlled release approach. In this work, a novel approach was developed for using gellan gum as a drug matrix and Gemcitabine loaded xanthan gum coated Fe3O4 magnetic nanoparticles (Gem: Xan (1%v/v)Fe3O4) as a drug carrier complex. The magnetization values were found to be 84.69 emu/g, 16.63 emu/g, and 9.91 emu/g for Fe3O4, Xan (1%v/v)Fe3O4, and Gem: Xan (1%v/v)Fe3O4, respectively. Notably, this work showcases the synthesis of Gemcitabine loaded xanthan gum coated magnetic nanoparticles as a new drug carrier complex, explores the drug release kinetics, and demonstrates the biocompatibility and non-toxicity of gellan gum on human skin, offering promising implications for transdermal drug delivery. The Gemcitabine release was 54 % without magnetic nanoparticles, and it increased to 82 % with the incorporation of magnetic nanoparticles. The Gemcitabine release – permeation of Gem: Xan (1%v/v)Fe3O4 was higher than that of the pristine Gemcitabine permeation by 72 %. The experimental results revealed that the magnetic field played a crucial role in controlling the drug release rate, amount, and duration during the release and release-permeation study.

Dandelion inspired microparticles with highly efficient drug delivery to deep lung

Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as ‘seed’ and could be delivered to alveoli aided by the low density ‘pappus’ composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of ∼ 68.96 % and extra fine particle fraction of ∼ 36.87 %, equivalently ∼ 4.60 mg and ∼ 2.46 mg could reach the lung and alveoli, respectively, when inhaling 10 mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.

Evaluation of Pediatric Patients Admitted to the Hospital for Drug Intoxication

Abstract Objective: Drug poisoning is the most common form of poisoning in children, and it is a situation that can lead to fatal consequences, but can be prevented if appropriate precautions are taken. Children are the future of a society, so drug poisoning poses an important public health problem. Factors such as high-dose drug combinations, misuse, poor storage conditions, and children's access to drugs can all contribute to drug intoxication. The aim of this study is to understand the effects of drug poisoning on children, to identify the characteristics of these children and to raise awareness about the measures that can be taken to prevent this problem. Material and Methods: This study was conducted retrospectively on 100 patients who applied to the pediatric emergency department of Karabuk University Faculty of Medicine Education and Research Hospital with the complaints of drug use and drug exposure. Results: It was observed that the mean age of the patients was 7.65±6.51 years, 58% of them were girls and 71% of them accidentally drank drugs. When the drugs consumed by the patients were examined, it was determined that the analgesic-anti-inflammatory (Paracetemol) group was the highest with 18%. When the hospitalization status of the patients was examined, it was seen that 22% of them were not hospitalized. It was observed that 56% of the patients experienced symptoms, and the most common symptom was nausea and vomiting with 33%. No mortality was observed in any of the patients. Conclusion: Study results show that children often take drugs accidentally. The fact that analgesic-antipyretic group drugs are mostly encountered suggests that it is a predictable result of their widespread use in the community. In addition, the high hospitalization rate with 78% unfortunately leads to an extra expenditure of our limited resources for a condition that could have been prevented. For this reason, establishing an effective public health policy and taking preventive measures for commonly used drugs can reduce the frequency of poisonings. We think that our findings will guide clinicians. Keywords: Drug poisoning, intoxication, drugs, pediatric patients

Synthesis, Characterization, Phytochemistry, and Therapeutic Potential of Azadirachta indica Conjugated Silver Nanoparticles: A Comprehensive Study on Antidiabetic and Antioxidant Properties.

Nanotechnology has become a major topic of study, particularly in the medical and health domains. Because nanomedicine has a higher recovery rate than other conventional drugs, it has attracted more attention. Green synthesis is the most efficient and sustainable method of creating nanoparticles. The current work used ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction to thoroughly characterize the synthesized silver nanoparticles (AgNPs) from Azadirachta indica leaf extract. Characterization confirmed the synthesis of the AgNPs along with the possible linkage of the phytochemicals with the silver as well as the quantitative analysis and nature of NPs. The antioxidant activity of AgNPs and neem extract was measured by the 2,2-diphenyl-1-picrylhydrazyl assay using various concentrations (20, 40, 60, 80, and 100µg/ml). Additionally, using diabetic mice that had been given alloxan, the in vivo antidiabetic potential of biosynthesized AgNPs was assessed. Eight groups of mice were used to assess the antidiabetic activity: one control group and seven experimental groups (untreated, extract-treated, AgNPs at low and high doses, standard drug, low dose of AgNPs + drug, and high dose of AgNPs + drug). At days 0, 7, 14, 21, and 28, blood glucose levels and body weight were measured. After 28days, the mice were dissected, and the liver, kidney, and pancreas were examined histologically. The results depicted that the AgNPs showed higher (significant) radical scavenging activity (IC50 = 35.2µg/ml) than extract (IC50 = 93.0µg/ml) and ascorbic acid (IC50 = 64.6µg/ml). The outcomes demonstrated that biosynthesized AgNPs had a great deal of promise as an antidiabetic agent and exhibited remarkable effects in diabetic mice given AgNPs, extract, and drug. Remarkable improvement in the body weight and blood glucose level of mice treated with high doses of AgNPs and drug was observed. The body weight and blood glucose level of diabetic mice treated with a high dose of AgNPs + standard drug showed significant improvement, going from 28.7 ± 0.2 to 35.6 ± 0.3g and 248 ± 0.3 to 109 ± 0.1mg/dl, respectively. Significant regeneration was also observed in the histomorphology of the kidney, liver's central vein, and islets of Langerhans after treatment with biosynthesized AgNPs. Diabetic mice given a high dose of AgNPs and drug displayed architecture of the kidney, liver, and pancreas that was nearly identical to that of the control group. According to the current research, biosynthesized AgNPs have strong antioxidant and antidiabetic potential and may eventually provide a less expensive option for the treatment of diabetes.

Synergistic Effect of Chemotherapy and Magnetomechanical Actuation of Fe-Cr-Nb-B Magnetic Particles on Cancer Cells.

The present study is aimed at developing an innovative method for efficient cancer cell destruction by exploiting the magnetomechanical actuation (MMA) of Fe-Cr-Nb-B magnetic particles (MPs), which are loaded with clinically approved chemotherapeutic drugs. To achieve this objective, Fe68.2Cr11.5Nb0.3B20 magnetic nanoparticles were produced by mechanically grinding amorphous ribbon precursors with the same composition. These nanoparticles display high anisotropy, a parallelepipedic shape with an amorphous structure, and a ferromagnetic behavior. MPs were loaded with the antitumoral drugs mitoxantrone (MTX) or doxorubicin (DOX). In our study, we used adipose-derived mesenchymal stem cells and human osteosarcoma cells to test drug-loaded MPs for their biocompatibility, cytotoxicity, and cellular internalization. Further tests involved exposing cells to magnetomechanical actuation and simultaneous MPs-targeted chemotherapy followed by cell viability/death assays, such as MTT and LDH, and live/dead cell staining. Results demonstrate that cancer cell death was induced by the synergistic action of chemotherapeutic drugs and magnetomechanical actuation. The nanoparticle vehicles helped overcome drug resistance, decreasing the high dose of drugs used in conventional therapies as well as the time intervals needed for MMA to affect cancer cell viability. The proposed approach highlights the possibility of using a new, targeted, and effective cancer treatment with very few side effects.

Construction of injectable micron-sized polymorphic vesicles for prolonged local anesthesia with weekly sustained release of ropivacaine

Currently, to overcome the short half-life of the local anesthetic ropivacaine, drug delivery systems such as nanoparticles and liposomes have been used to prolong the analgesic effect, but they are prone to abrupt release from the site of administration or have poor slow-release effects, which increases the risk of cardiotoxicity. In this study, injectable lipid suspensions based on ropivacaine-docusate sodium hydrophobic ion pairing (HIP) were designed to significantly prolong the duration of analgesia. The resulting ion-paired lipid suspension (HIP/LIPO) had a micrometer scale and a high zeta potential, which facilitates stable in situ retention. The strong interaction between docusate sodium and ropivacaine was verified using thermal and spectroscopic analyses, and the formation of micron-sized polymorphic vesicles was attributed to the mutual stabilizing interactions between ropivacaine-docusate sodium HIP, docusate sodium and lecithin. The HIP/LIPO delivery system could maintain drug release for more than 5 days in vitro and achieve high analgesic efficacy for more than 10 days in vivo, reducing the side effects associated with high drug doses. The stable HIP/LIPO delivery system is a promising strategy that offers a clinically beneficial alternative for postoperative pain management and other diseases.