Injection Of Dose Research Articles

Assessment of milk biosafety for the content of antiparasitic drugs used for human consumption in different countries: Review

Milk is a staple food consumed all over the world which has significant impact both economically and nutritionally. Even if the milk is nutritious and healthful, it can also contain antiparasitic drugs residues that dangerous to human health. Inappropriate using antiparasitic drugs for producing animals may cause serious disorder in humans. This review was aimed to find out and analyze how much the dosage of injections and the excretion period of antiparasitic drugs from animal milks have been studied for safe human consumption. Totally, 15 papers about antiparasitic drugs usage for different animals were analyzed. The results showed that the most studied animal to date is the cow for ivermectin, albendazole and abamectin residues. More research works are required to be done for animals as goats, sheep, and especially camels to know after how many periods of time antiparasitic drugs will be excreted. As camel milk gains popularity due to it is possessing therapeutic and immunostimulant properties, more experimental results are needed into veterinary drugs safety measures. One of the mainly used method to conduct experiment is high-performance liquid chromatography because of superior resolving power when separate mixtures.

Ozurdex insert dislocated to the anterior chamber after postration in a patient who underwent secondary implant surgery with Canabrava technique: A case report

Aims/Purpose: To present a case report of a 64‐year‐old man with dislocation of a dexamethasone anterior chamber (AC) implant, who underwent secondary implantation with the Canabrava technique.Methods: A male patient underwent surgery for a secondary implant in the left eye using the Canabrava technique.Post‐operatively, cystic macular oedema was observed on optical coherence tomography (OCT). After 15 days, with no anatomical improvement despite treatment with Nevanac eye drops, a dose of intravitreal injection with Ozurdex® was prescribed. A few days later, the patient came to the emergency department and reported seeing a foreign body in the treated eye. On biomicroscopic examination, an Ozurdex® insert was found in the AC. When the patient was questioned again, he stated that he had been in the praying position the previous days. A new macular OCT was performed, showing resolution of the foveal oedema. Dilation of the LAA with phenylephrine was performed with cephalic manoeuvres in the supine decubitus position, achieving the repositioning of the dexamethasone implant in the vitreous chamber. Finally, an OCT of the anterior pole shows that the secondary implant is normally positioned without complications.Results: After initial treatment with Ozurdex® intravitreal implant, total resolution of the post‐operative cystic macular oedema is achieved, even with dislocation to the anterior chamber. After outpatient management of the dislocation of the implant, we were able to relocate it to the vitreous chamber without the need for surgical management of the patient.Conclusions: In the clinical case, it is demonstrated that the anti‐inflammatory effect of Ozurdex® remains active despite dislocation of the implant to the anterior chamber. Likewise, a good ambulatory technique in the supine position with directed cephalic manoeuvres may be sufficient to reposition the implant without the need for surgery.

T Cell Receptor-Engaging Monoclonal Antibodies Mobilize the Anti-Tumor Functions of Invariant Natural Killer T Cells.

Invariant natural killer T cells (iNKTs) are innate-type T lymphocytes that directly kill tumor cells or tumor-growth promoting immunosuppressive cells such astumor-associated macrophages. Additionally, iNKTs robustly transactivate the antitumor functions of T, B, natural killer, and dendritic cells as well as reinvigorate exhausted immune cells in the tumor microenvironment. As such, iNKTs make excellent candidates for inclusion in anti-cancer cellular therapies. However, to capitalize on the potential benefits of iNKT cell-based approaches, it is imperative that we develop new and clinically viable strategies to enhance their antitumor function. To that end, two novel monoclonal antibodies (mAbs) that selectively bind to the human (NKTT320) or murine (NKT14m) invariant T cell receptor have been recently developed and characterized. Studies using purified human iNKTs (in vitro) and a model of non-human primate (in vivo) reveal that NKTT320 promotes swift, vigorous and sustained iNKT cell activation that is accompanied by robust production of inflammatory mediators and bystander immune cell activation. Furthermore, NKTT320 augments expression of cytotoxic markers and human iNKT cell degranulation. Similarly, NKT14m prompts dramatic murine iNKT cell activation and functional response both in vitro and in vivo. However, antitumor efficacy of a single dose of NKT14m injection in tumor-bearing mice is limited and tumor-model dependent. In contrast, combination treatment of NKT14m with either low dose interleukin (IL)-12 or the chemotherapeutic agent, cyclophosphamide results in a superior antitumor response in vivo. This is evident by activation of both iNKTs and other immune cells, prolonged survival of the tumor-challenged mice, and long-lasting immunity. Collectively, these recent studies justify further development of anti-iTCR mAbs that can be used alone or in conjunction with immunomodulatory agents to enhance iNKT cell antitumor immunity against various cancers.

Human umbilical cord mesenchymal stem cells toxicity and allergy effects: In vivo assessment.

Human umbilical cord mesenchymal stem cells (hUCMSCs) hold significant promise across various clinical applications. Therefore, regulatory requirements necessitate a thorough investigation of the hUCMSCs safety before clinical trials and potential allergic reactions after transplantation. Abnormal toxicity test employed mice and guinea pigs dosed daily at 0.5×106 cells and 5×106 cells, respectively for 7 days. Acute toxicity test employed low, medium, and high doses of hUCMSCs injected into mice once, followed by observations for 23 days. In systemic allergy test, guinea pigs received low and high dose of hUCMSCs, with sensitization and excitation stages at day 14 and 21, respectively. The abnormal toxicity test of hUCMSC injections revealed no abnormal reactions over a seven-day observation period, indicating the safety of this administration route. In acute toxicity studies, the high-dose hUCMSCs group resulted in fatalities due to pulmonary embolism. Conversely, the low-dose group exhibited no toxic reactions or deaths. The maximum tolerated dose was determined to be >2×107 cells/kg. Systemic active allergy test showed that high doses of hUCMSC intravenous injections did not induce allergic reactions. This research affirms hUCMSC injections meet safety standards for clinical cell therapy, emphasizing their safe and promising clinical utility.

Cytidine does not affect acute toxicity of intravenously administered choline.

Cytidine-5'-diphosphocholine (CDP-choline) is a key precursor for the intracellular synthesis of phosphatidylcholine and other phospholipids. Following either intravenous or oral application citicoline (CDP-choline of exogenous origin) undergoes quick decomposition to cytidine and choline, and for this reason it is frequently considered a prodrug. However, upon acute intravenous application in mice citicoline is, on a molar basis, 20 times less toxic than choline. To find out whether cytidine may attenuate toxicity of choline, in the present experiments we compared maximum tolerated doses of single intravenous injections of choline and equimolar mixture of choline and cytidine. We assumed that, if after oral intake a substantial part of citicoline is catabolised already in the intestine and its catabolites enter blood separately, intravenously applied equimolar mixture of cytidine and choline will be markedly less toxic than an equivalent molar dose of choline. However, the maximum tolerated single doses determined in our experiment for choline and equimolar mixture of choline and cytidine were similar. These data suggest that citicoline taken orally is not significantly decomposed in the intestinal lumen, but absorbed to blood as the intact molecule.

The effect of single dose of gonadotropin-releasing hormone agonist injection in frozen-thawed embryo transfer on pregnancy outcomes: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomized controlled trials aimed to evaluate the effect of a single-dose gonadotropin-releasing hormone agonist administration in the frozen-thawed embryo transfer cycle on pregnancy outcomes. A literature search was strategically conducted using PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary outcome was the clinical pregnancy rate. The secondary outcomes combined chemical pregnancy rate, implantation rate, ongoing pregnancy rate, live birth rate, miscarriage rate, and extrauterine pregnancy rate. Out of the 1594 citations that were found, only six met the criteria for being included in the meta-analysis. The clinical pregnancy rate was higher in the treatment group than in the control group (52.05% vs. 47.29%; p=0.04; RR=1.09; 95% CI=1.00-1.18). According to subgroup analysis based on the natural cycle, the clinical pregnancy rate with the agonist administration is significantly higher (43.75% vs. 27.35%; p=0.01; RR=1.6; 95% CI=1.10-2.32). However, there was no difference between the groups in terms of artificial cycles (p=0.80; 95% CI=0.96-1.20). The secondary outcomes did not show significant differences. We concluded that supplementing with a single dose of gonadotrophin-releasing hormone agonist can marginally increase the clinical pregnancy rate, particularly in the natural cycle. Other pregnancy outcomes do not improve with the treatment.

Comparing the Effects of Allicin and Thymoquinine on type 1 Diabetes

Introduction: Nigella sativa (Black seed) and Allium sativum (garlic), are common dietary spices also traditionally used as a treatment for various diseases including diabetes mellitus. The antidiabetic activity of each individual spice is well documented.Purpose: This study aimed to compared the effect of the active ingredients of nigella sativa (Thymoquinone) and allium sativa (Allicin) on STZ induced type 1 diabetes in rats' model.Materials and Methods: Six equal sized groups of rats were used in this experiment. Five groups were injected with STZ to induce type 1 diabetes. Four groups received a daily dose of intraperitoneal injection of one of the following: 5mg/kg of Thymoquinone, 10mg/kg of Thymoquinone, 8mg/kg of Allicin, and 16 mg/kg of Allicin for four weeks. One STZ treated group was used as a positive control and the last non treated group was used as a negative control. At the end of the experimental period, the body weights, fasting glycose levels and insulin levels were tested and compared among these groups. Results: The results of the four treated groups were compared to the negative and positive control groups. The body weight for all four treated groups increased especially the group treated with 8mg/kg Allicin compared to the positive control group. FBG levels for all treated groups was also decreased. The group treated with 8mg/kg Allicin showed the best result where the FBS level were within the normal level by the end of the month. The group treated with 16mg/kg Allicin showed the best result for insulin level where it was restored by 79.26% compared to the control group. The other treated groups showed a very close results at the end of the month. The histology of pancreatic islets showed similar ameliorating effects in all of the four treated groups when compared to the positive control group. Conclusion:In conclusion, these experimental results indicate the use of Allicin showed the best impact on type 1 diabetes treatment.

A Study to Assess the Efficacy of Ultrasound-guided Bilateral Erector Spinae Plane Block for Total Abdominal Hysterectomy under Spinal Anesthesia: A Prospective Randomized Control Study

Abstract Background: Postoperative discomfort after a total abdominal hysterectomy (TAH) is severe. The Erector spinae plane block (ESPB) is the latest addition to the multimodal pain management regimen, providing both visceral and somatic analgesia. Aim: The aim of this study was assessed the postoperative analgesic efficacy of ultrasound-guided bilateral ESPB for TAH. Materials and Methods: 70 female patients aged 40 to 60 years, American society of anaesthesiology (ASA) physical status class I and II posted for TAH were enrolled. Group ESPB+SA(n=35) received bilateral ESPB using 0.25% ropivacaine hydrochloride 15ml with 0.5µ/kg dexmedetomidine on each side before spinal anaesthesia, while group SA (n=35) received only spinal anaesthesia. Postoperative follow-up for 24 hours.Statistical analysis used: Independent-samples student t-test. Results: The total dose of tramadol injection consumed in the first 24 hours postoperatively in group ESPB+SA was significantly low (110.34mg) as compared to group SA (334.29mg) (P < 0.001). Time for first rescue analgesia was prolonged significantly in group ESPB+SA while it was very short in Group SA(P < 0.001). Postoperatively the mean modified defense and veterans pain rating scale (DVPRS) for pain was lower in group ESPB+SA than in group SA, and the difference was statistically significant (P < 0.001). Similarly, scores for other modified DVPRS components, such as sleep, activity, mood and stress were lower in the ESPB+SA group. Conclusions: Bilateral ultrasound-guided ESPB prior to spinal anaesthesia offers effective and prolonged postoperative analgesia, with significantly lower postoperative tramadol use and a higher satisfaction score in patients undergoing TAH under spinal anaesthesia.

A Mouse Model of Hepatocellular Carcinoma Induced by Streptozotocin and High-Fat Diet.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the second most common cause of cancer-related death. HCC is associated to chronic diseases such as viral hepatitis, alcoholic, and non-alcoholic fatty liver disease (NAFLD), diabetes mellitus, and obesity, among others. Although pre-clinical models have been investigated to mimic the transition from NAFLD to HCC, they do not accurately reproduce the phenotypic evolution from simple steatosis to steatohepatitis, fibrosis/cirrhosis, and HCC. Hence, these models have failed to demonstrate the influence of diabetes on hepatic carcinogenesis. Here, we report a novel mouse model of HCC triggered by fast-developing diabetes and NAFLD. The first step consists in a single intraperitoneal injection of a low dose of streptozotocin into neonatal C57BL/6J mice to induce type 2 diabetes. In a second step, mice are fed with high-fat diet to accelerate the development of simple steatosis. Continuous high-fat diet exacerbates hepatic fat deposition with increased lobular inflammation (by activation of foam cell-like macrophages) and fibrosis (by activating hepatic stellate cells), two representative pathological traits of steatohepatitis/fibrosis. After 20weeks, all mice developed multiple HCCs. This model of hepatic carcinogenesis triggered by diabetes mellitus and NAFLD offers the advantage of being rapid and accurately recapitulates the pathogenesis of human HCC without the need of administering hepatic carcinogens.

Effect of aqueous-alcoholic extract of Ducrosia Anethifolia Boiss on the fetal liver of diabetic rats

Objective: Moshgak (Ducrosia anethifolia) is a wild plant with medicinal value. The present study aimed to evaluate the effect of Moshgak on the liver tissue of the diabetic rat fetus. Materials and Methods: In this animal study, the aqueous-alcoholic extract of Moshgak was prepared in the standard method. Forty rats were divided randomly into five groups, including control, sham, and three diabetic groups. The rats were diabetic with intraperitoneal injection of a single dose of streptozotocin (80 mg) and 2 diabetic groups were treated with Moshgak extract (280 and 560 mg/kg/bw) for 19 days. The rats were anesthetized and their blood was taken to measure the blood glucose, insulin, and malondialdehyde. Then, their fetuses were removed. The fetal liver sections were obtained by using the stereological methods. The micrometry of the liver tissue was performed and data were analyzed. Results: The finding showed a statistically significant increase (P < 0.01) in the total volume of liver, connective tissue, sinusoid, and hepatocytes in diabetic rats compared to control rats, while these parameters decreased significantly in treated groups with Moshgak. Hepatic cell count hepatic decreased in the treated groups. Furthermore, the changes in blood glucose, malondialdehyde, and insulin in diabetic rats were improved significantly by Moshgak treatment. The dilation of sinusoids, hepatocyte vacuolation, and mild lymphocytosis was observed in all diabetic groups except the treatment group with Moshgak 560 mg/kg/bw. Conclusions: According to obtained results, Moshgak extract was able to compensate partially the changes induced by diabetes in the fetal liver tissue. Therefore, due to the side effects of diabetes during pregnancy, further research on anti-diabetic properties of Moshgak is suggested.

Inactivation of the NLRP3 inflammasome mediates exosome-based prevention of atrial fibrillation.

Rationale: Extracellular vesicles (EVs) from human explant-derived cells injected directly into the atria wall muscle at the time of open chest surgery reduce atrial fibrosis, atrial inflammation, and atrial fibrillation (AF) in a rat model of sterile pericarditis. Albeit a promising solution to prevent postoperative AF, the mechanism(s) underlying this effect are unknown and it is not clear if this benefit is dependent on EV dose. Methods: To determine the dose-efficacy relationship of EVs from human explant-derived cells in a rat model of sterile pericarditis. Increasing doses of EVs (106, 107, 108 or 109) or vehicle control were injected into the atria of middle-age male Sprague-Dawley rats at the time of talc application. A sham control group was included to demonstrate background inducibility. Three days after surgery, all rats underwent invasive electrophysiological testing prior to sacrifice. Results: Pericarditis increased the likelihood of inducing AF (p<0.05 vs. sham). All doses decreased the probability of inducing AF with maximal effects seen after treatment with the highest dose (109, p<0.05 vs. vehicle). Pericarditis increased atrial fibrosis while EV treatment limited the effect of pericarditis on atrial fibrosis with maximal effects seen after treatment with 108 or 109 EVs. Increasing EV dose was associated with progressive decreases in pro-inflammatory cytokine content, inflammatory cell infiltration, and oxidative stress. EVs decreased NLRP3 (NACHT, LRR, and PYD domains-containing protein-3) inflammasome activation though a direct effect on resident atrial fibroblasts and macrophages. This suppressive effect was exclusive to EVs produced by heart-derived cells as application of EVs from bone marrow or umbilical cords did not alter NLRP3 activity. Conclusions: Intramyocardial injection of incremental doses of EVs at the time of open chest surgery led to progressive reductions in atrial fibrosis and inflammatory markers. These effects combined to render atria resistant to the pro-arrhythmic effects of pericarditis which is mechanistically related to suppression of the NLRP3 inflammasome.

Advancing Patient Blood Management: Evaluation of Ferric Derisomaltose in a Tertiary Hospital

ABSTRACT Background and Objectives: One of the aims of patient blood management (PBM) programs is to improve patient outcomes by managing anemia and avoiding unnecessary blood transfusions. Ferric derisomaltose (FDI) is a treatment that allows for the injection of high doses of iron in a shorter time, which makes it a promising approach for correcting iron-deficiency anemia (IDA) more efficiently. This study aimed to assess the safety, effectiveness, and cost implications of FDI in a PBM program and its impact on transfusion requirements. Methods: A retrospective analysis was conducted on electronic medical records of adult patients diagnosed with IDA who received FDI as part of a PBM strategy in a tertiary hospital from November 2019 to June 2021. Descriptive statistics summarized patient characteristics and outcomes. Changes in hemoglobin (Hb) levels were evaluated using a paired t-test. Cost analysis included direct and indirect expenses associated with FDI administration compared to alternative treatments. Results: Out of the initially enrolled 110 patients, 67 were included in the analysis. A mean increase in Hb levels of 2.7 ± 1.9 g/dL was observed as early as 4 days post-FDI administration. The majority of patients (94.0%) tolerated FDI well, with only a few experiencing mild adverse reactions. Following FDI administration, blood transfusion was avoided by 88% of patients. Cost analysis revealed that while FDI demonstrated higher direct costs compared to alternative treatments, its potential for lower total costs became apparent when considering both direct and indirect expenses. Conclusions: FDI demonstrated promising results in rapidly correcting IDA within a PBM program. It reduced the need for blood transfusions, with the treatment being well-tolerated by patients. The inclusion of FDI administration in PBM programs offers a convenient, efficient, and potentially cost-effective approach to managing IDA.

Determinants of medication adherence and impact of mobile telephony, pillbox interventions on compliance and glycemic control among patients with type 2 diabetes

Abstract Background: Medication adherence has been linked to improved glycemic control, fewer complications from diabetes, fewer hospitalizations, reduced health care expenses, and a decreased mortality rate. The medication adherence pattern, reason, and factors associated with poor medication adherence among patients living with type 2 diabetes mellitus were determined, and the impact of two interventions to improve medication adherence was assessed. Materials and Methods: The medication adherence patterns of 240 people living with diabetes were determined using the Morisky Green Levine Medication Adherence Scale-4 and categorized into low, medium, and high adherence patterns. Patients with poor medication adherence (low and medium pattern) scores were randomized into short message service (SMS) and pillbox interventions, and the impact of Interventions on compliance and glycemic control was determined. Results: Results demonstrate that 3% of patients living with type 2 diabetes have low, 43% medium, and 54% have high medication adherence patterns. The most common reason cited for non-adherence was (88%) followed by lack of finance (5%) and multiple medications (4%). A positive association of injectable dosage forms, number of drugs, and treatment modalities with adherence was found. SMS and pillbox intervention improved medication adherence among individuals with diabetes who had poor adherence, which translated into good glycemic control. Conclusions: The improvement in drug compliance and glycemic control was found to be equivocal among the SMS and pillbox intervention groups. The inclusion of interventions into the institutional education program and counseling by health care workers will motivate patients to adopt these interventions to improve drug compliance and glycemic control.

A nanocarbon-enabled hybridization strategy to construct pharmacologically cooperative therapeutics for augmented anticancer efficacy.

The drug design principles are of great value in developing nanomedicines with favorable functionalities. Herein we propose a nanocarbon-enabled hybridization strategy to construct a pharmacologically cooperative nanodrug for improved cancer therapy in the light of pharmacophore hybridization in medicinal chemistry and the synthetic principles of nanocarbons. An antioxidant defense pharmacological inhibitor and a co-nucleation precursor are structurally hybridized into nanodrugs (SCACDs) via forming carbon quantum dots. These SCACDs elicit dual enhanced bioactivities, including superior sonocatalytic activity that arose from the appropriate band structure of the pharmacophoric carbon cores, and more than an order of magnitude higher antioxidant defense inhibitory activity than the pharmacological inhibitor via conveying the bioactive pharmacophores from the molecular level to nanoscale. In vivo, SCACDs possess a long body retention and desirable biodistribution to eliminate melanoma cells at a very low injection dose. The present study provides a viable yet effective strategy for the development of pharmacologically cooperative nanodrugs to achieve remarkably improved therapeutic efficacy.

Validation of Quantitative Accuracy and Variability in 177Lu Imaging Using Monte Carlo Simulation

To predict side effects and optimize injection doses in the dosimetry of 177Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for 177Lu imaging under various imaging conditions. SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of 177Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation. The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time. Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for 177Lu imaging.

Accuracy of Injection Dose of Amyloid PET Agent Using Radiopharmaceutical Activity Suppliers

This study aimed to identify disposable items with low amyloid positron emission tomography (PET) agent radioactivity adsorption for accurate injections using a radiopharmaceutical activity supplier. First, we investigated disposable items currently used for amyloid PET agent injection. Next, we measured the residual radioactivity rates of amyloid PET agents on three-way stopcocks, extension tubes, butterfly needles, and indwelling needles to identify disposable items with low radioactivity adsorption. Finally, we evaluated the accuracy of amyloid PET agent injection using the selected disposable items and a radiopharmaceutical activity supplier. The polybutadiene extension tube exhibited a significantly lower residual activity rate than that of the polyvinyl chloride extension tube. Similarly, the indwelling needles showed significantly lower residual activity rate than that of butterfly needles. The dose indicated by a radiopharmaceutical activity supplier was 184.1 MBq, while the dose calibrator measured the radioactivity which flowed into the vial as 170.2 MBq, resulting in an administration accuracy of 8.2%. To ensure accurate amyloid PET agent injections, we recommend using polybutadiene extension tubes and indwelling needles due to their lower radioactivity adsorption.

Evaluation of the Effect of Buparvaquone Used in the Treatment of Neonatal Calves Naturally Infected with Cryptosporidium Spp. on Renal and Hepatic Functions

Cryptosporidium parvum is a zoonotic protozoan that causes neonatal calf diarrhea common in the world. Buparvaquone, which is known to have very positive effects on oocysts, which are the main reserve in the spread of infection, has not yet been investigated for its hemato-biochemical aspect in calves with cryptosporidiosis. In the present study, the effect of buparvaquone on renal and hepatic functions in naturally infected newborn calves with cryptosporidiosis was investigated. A group was formed for this study using only a total of ten calves (n=10) naturally infected with cryptosporidiosis. Buparvaquone 2.5 mg/kg intramuscular injection was administered as a single dose to all calves in the group. Laboratory analyses and statistical calculations of blood and serum samples taken on the specified days were made. According to the results we obtained in the study, it was observed that the renal and hepatic effects of the drug after a single dose injection of buparvaquone to calves with neonatal cryptosporidiosis remained within normal limits, similar to the methods safely applied in the treatment of cryptosporidiosis in the field.

Hematological Profile and Aminotransferase Activity in Kintamani Bali Puppies Injected with High Doses of Ivermectin

Pr Ivermectin toxicity is known to cause harmful side effects or even death in dogs intolerant to the medication. Intolerant dogs have a mutation in the MDR-1 (Multi-Drug Resistance) gene, so they lack the P-glycoprotein gene that removes drugs from the brain. Therefore, this study aimed to determine ivermectin toxicity in Kintamani Bali puppies by examining physiological responses based on hematological profiles and aminotransferase activity after a high-dose injection. A laboratory observational approach was used, and the samples were 25 healthy female Kintamani puppies based on a veterinary examination, aged 3-6 months, weighing 6.32 ± 1.18 kg, randomly divided equally into five treatment groups. The treatments included a placebo (1ml Aqua Pro Injection) as a control, as well as a single dose of ivermectin injection sequentially 200, 400, 800, and 1600 µg/kg subcutaneously. Blood samples were collected before treatment and after 7 and 14 days post-treatment. The hematologic parameters observed included levels of hemoglobin, erythrocytes, hematocrit, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, as well as blood biochemistry, namely aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Observation results after 4 hours of administration of ivermectin at doses of 800 and 1600 µg/kg of puppies showed changes in behavior, restlessness, depression, tremors, mydriasis, hypersalivation, anorexia, and polydipsia. Meanwhile, the results of hematological examination on the seventh day after ivermectin treatment showed a trend of erythropenia, leukocytosis, a decrease in hemoglobin levels, and an increase in aminotransferase enzyme activity. This condition continued until day 14, but the physiological parameter values showed that the puppy’s condition gradually improved compared to the seventh day after treatment. There were significant differences in the blood profile, AST, and ALT of Kintamani puppies injected with ivermectin at doses of 800 and 1,600 ug/kg compared to controls on days 7 and 14 after and before treatment. It was concluded that high-dose ivermectin injections in Kintamani Bali puppies caused toxicity with clinical signs of erythropenia, decreased hemoglobin, leukocytosis, and increased aminotransferase activity.

Formulation Development and Evaluation of Highly Oxidative Degradative Drug Molecule Injectable Dosage form by Lyophilisation Techniques

Adrenaline (ADR) It is lifesaving and is the only first-line drug for the treatment of anaphylaxis. Adrenaline (ADR) is the endogenous catecholamine with potent alpha- and beta-adrenergic stimulating properties. Alpha-adrenergic action increases systemic and pulmonary vascular resistance, increasing both systolic and diastolic blood pressure. Adrenaline is released in the bloodstream, which increases heartbeat, muscle strength, blood pressure, and glucose metabolism. Oxidation degradation of the medicinal product is the main route of degradation. Affects chemical and physical changes in drugs during the formulation development process. Physicochemical changes in the product can affect both the safety and efficacy of the drug product. Main product development strategy to develop, a stable, freeze-dried product of epinephrine for injection. The stability of adrenaline injection is of paramount objective as it is classified as a catechol compound that is sensitive to oxidation to o-quinone and therefore can react further to form highly colored compounds. Adrenergic drugs further react to form adrenochrome, a highly colored indole derivative. The rate of this reaction increased with pH, temperature and presence of the metal ions. Aqueous solutions of adrenergic agonists decompose rapidly when exposed to air, light, or heat, turning pink due to oxidation to adrenochrome and brown due to melanin formation. Due to its strong oxidizing properties and easy decomposition in aqueous solutions. To achieve this, the aqueous solutions of adrenergic agonists decompose rapidly when exposed to air, light, or heat, turning pink due to oxidation to adrenochrome and brown due to melanin formation. Due to its strong oxidizing properties and easy decomposition in aqueous solutions.

CU06-1004 alleviates oxidative stress and inflammation on folic acid-induced acute kidney injury in mice

PurposeAcute kidney injury (AKI) is characterized by reduced renal function, oxidative stress, inflammation, and renal fibrosis. CU06-1004, an endothelial cell dysfunction blocker, exhibits anti-inflammatory effects by reducing vascular permeability in pathological conditions. However, the potential effects of CU06-1004 on AKI have not been investigated. We investigated the renoprotective effect of CU06-1004 against oxidative stress, inflammation, and fibrotic changes in a folic acid-induced AKI model. MethodsAKI was induced by intraperitoneal injection of high dose (250 mg/kg) folic acid in mice. CU06-1004 was orally administered a low (10 mg/kg) or high dose (20 mg/kg). ResultsCU06-1004 ameliorated folic acid-induced AKI by decreasing serum blood urea nitrogen and creatinine levels, mitigating histological abnormalities, and decreasing tubular injury markers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in folic acid-induced AKI mice. Additionally, CU06-1004 alleviated folic acid-induced oxidative stress by reducing 4-hydroxynonenal and malondialdehyde levels. Furthermore, it attenuated macrophage infiltration and suppressed the expression of the proinflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion protein-1. Moreover, CU06-1004 mitigated folic acid-induced tubulointerstitial fibrosis by decreasing α-smooth muscle actin and transforming growth factor-β expression. ConclusionThese findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.