Injection Of Dose Research Articles

Role of hippocampal and prefrontal cortical cholinergic transmission in combination therapy valproate and cannabidiol in memory consolidation in rats: involvement of CREB- BDNF signaling pathways.

Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function. This study examined the effects of co-administration of CBD and valproate on memory consolidation, cholinergic transmission, and cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in the prefrontal cortex (PFC) and hippocampus (HPC). One-trial, step-through inhibitory test was used to evaluate memory consolidation in rats. The intra-CA1 injection of physostigmine and atropine was performed to assess the role of cholinergic transmission in this co-administration. Phosphorylated CREB (p-CREB)/CREB ratio and BDNF levels in the PFC and HPC were evaluated. Post-training intraperitoneal (i.p.) valproate injection reduced memory consolidation; however, post-training co-administration of CBD with valproate ameliorated memory impairment induced by valproate. Post-training intra-CA1 injection of physostigmine at the ineffective doses in memory consolidation (0.5 and 1µg/rat), plus injection of 10mg/kg of CBD as an ineffective dose, improved memory loss induced by valproate, which was associated with BDNF and p-CREB level enhancement in the PFC and HPC. Conversely, post-training intra-CA1 injection of ineffective doses of atropine (1 and 2µg/rat) reduced the positive effects of injection of CBD at a dose of 20mg/kg on valproate-induced memory loss associated with BDNF and p-CREB level reduction in the PFC and HPC. The results indicated a beneficial interplay between valproate and CBD in the process of memory consolidation, which probably creates this interaction through the BDNF-CREB signaling pathways in the cholinergic transmission of the PFC and HPC regions.

Differences in the microbiome of the small intestine of Leghorn lines divergently selected for antibody titer to sheep erythrocytes suggest roles for commensals in host humoral response.

For forty generations, two lines of White Leghorn chickens have been selected for high (HAS) or low (LAS) antibody response to a low dose injection of sheep red blood cells (SRBCs). Their gut is home to billons of microorganisms and the largest number of immune cells in the body; therefore, the objective of this experiment was to gain understanding of the ways the microbiome may influence the differential antibody response observed in these lines. We achieved this by characterizing the small intestinal microbiome of HAS and LAS chickens, determining their functional microbiome profiles, and by using machine learning to identify microbes which best differentiate HAS from LAS and associating the abundance of those microbes with host gene expression. Microbiome sequencing revealed greater diversity in LAS but statistically higher abundance of several strains, particularly those of Lactobacillus, in HAS. Enrichment of microbial metabolites implicated in immune response such as lactic acid, short chain fatty acids, amino acids, and vitamins were different between HAS and LAS. The abundance of several microbial strains corresponds to enriched host gene expression pathways related to immune response. These data provide a compelling argument that the microbiome is both likely affected by host divergent genetic selection and that it exerts influence on host antibody response by various mechanisms.

Reported side-effects following Oxford/AstraZeneca COVID-19 vaccine in the north-west province, Iran: A cross-sectional study.

While the vaccination was introduced as a promising tool to control the Coronavirus disease 2019 (COVID-19) pandemic, concerns about vaccine-related side effects had grown. Due to the widespread administration of the COVID-19 vaccine worldwide for the first time, it was necessary to evaluate the safety and potential side effects in recipients. This study aims to assess, the incidence of adverse effects following Oxford-AstraZeneca vaccination and identify their related factors. In this cross-sectional survey-based study, 453 volunteers participated, including 235 men and 218 women. The reported adverse reactions from recipients of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine were collected by using a questionnaire. The findings showed that the incidence of adverse reactions, such as neurological, systematic, gastrointestinal, respiratory, and local symptoms were significantly higher after the first dose compared to the second dose. Systematic symptoms were the most prevalent reported side effects after the first and second dose injection. The demographical study of participants showed that individuals aged 18-34 and females were more prone to present adverse events following vaccination. However, no significant relationship was found between the occurrence of side effects and the recipients' body mass index. Despite the life-saving role of vaccination against SARS-CoV-2, it may have some adverse reactions in recipients. The severity and frequency of side effects were different. So, they were dependent on several factors, including gender and age. Altogether, post-vaccination adverse reactions were mild and tolerable.

Design and manufacture a syringe pump for intelligent injection of specific doses of contrast medicine in medical imaging applications

The construction of an Arduino Uno based syringe pump with the ability to measure the patient's body temperature during injection and detect the contrast material bubble has not been done so far. A syringe pump is a device that controls the volume and flow of milliliters to microliters for a certain period of time with very high precision, which gradually pushes the injection piston. This use of syringe pump for drug administration has been done for years. The working principle of this system consists of installing two steel rods to push the syringe piston at a set speed, which works through a coupling system. The advancement of technology has made it possible to use a motor as the driving force of the syringe filled with liquid released through the needle, and the electronic system in this tool is used as a controller. The design using a stepper motor based on Arduino Uno is chosen to adjust the flow rate; the research includes two stages of software and hardware construction. The hardware is implemented with the components needed to build a syringe pump with an Arduino Uno as the brain of the system and a stepper motor as a piston pusher.The flow rate in the syringe pump can be adjusted with the keyboard and displayed on the screen. It is also possible to see the patient's body temperature on the screen, and to detect bubbles in the contrast liquid during injection, we also put a sensor in this device that alerts the operator.

Polyphenol-Standardized Aphanamixis polystachya Leaf Extract Ameliorates Diabetes, Oxidative Stress, Inflammation, and Fibrosis in Streptozotocin-Induced Diabetic Rats

Background. Diabetes is a rising disorder that affects millions of people annually. It also creates more complications, such as neuropathy, oxidative stress, and hepatic and kidney impairment. Aphanamixis polystachya plant, which possesses multiple medicinal values, is used in this study to explore its potential in treating diabetes. Methods. A single dose (65 mg/kg) of intraperitoneal streptozotocin injection was utilized to mediate diabetes in Sprague-Dawley rats. Diabetic animals were treated orally with 250 or 500 mg/kg of standardized leaves’ extract of A. polystachya (AP) for 28 days to evaluate the antidiabetic and organ-protective effects of the plant. Different biochemical and histological markers are measured according to the established protocol. Results. Our results demonstrated a significant decrease in blood glucose (p <0.001) and HbA1c (p <0.05) levels in the diabetic animal after administering AP (250 and 500 mg/kg doses) compared to the control groups. AP can also regularize lipids, glycogen, alanine aminotransferase, and aspartate aminotransferase. Furthermore, serum urea nitrogen and creatinine decreased after treatment with AP in diabetic rats. AP also reduced oxidative stress markers and showed a substantial elevation in antioxidant enzymes in diabetic animals. Overall, AP at 500 mg/kg revealed comparable results against the standard antidiabetic drug glyburide. Besides, the histological investigation showed the AP’s efficacy in attenuating kidney tissue inflammation and damage. HPLC data elucidated that the AP leaf extract contains polyphenols with potential antioxidant, antidiabetic, and organ protective agents: gallic acid, rutin hydrate, and quercetin hydrate. Conclusion. Taken together, AP may be one of the potential sources of antidiabetic agents.

Assessing the Efficacy and Safety of Intradermal Injection of Different Doses of Botulinum Toxin Type A: A Randomized, Double‐Blind, Placebo‐Controlled, Split‐Face Pilot Study in Rosacea Patients with Erythematic Telangiectasia

Introduction. Rosacea is a common chronic inflammatory skin disease of the central facial skin with unknown origin, significantly impacting quality of patient’s life and causing various psychosocial problems. Erythematotelangiectatic rosacea (ETR) is characterized by paroxysmal flushing that occurs repeatedly and is easily resistant to therapeutic drugs. While microinjection of type A botulinum toxin (BTX) can treat ETR, there is no consensus on the injection dose, and strong evidence to verify its efficacy and safety is lacking. This randomized, double‐blind, split‐face clinical study aimed to investigate the efficacy, safety, and optimal dose of two different single‐point injection doses (0.5 U and 1 U) of BTX in the treatment of rosacea. Methods. Twenty‐six patients with ETR were randomly assigned to receive different single‐point injections of BTX (0.5 U and 1 U, respectively) every 1 cm on one half of the face. The Clinical Erythema Score (CEA), VISIA red area absolute value, Global Aesthetic Improvement Scale Score (GAIS), and recurrence at 12‐week follow‐up were evaluated at baseline, 2,4, 8, and 12 weeks after injection. Additionally, the Dermatological Quality of Life Index (DLQI) questionnaire survey and adverse reactions were also recorded. Results. All twenty‐six patients completed the follow‐up visits and were included in the analysis. Compared to the 0.5 UBTX‐treated side, the CEA score showed significantly improvement in erythema and flushing at 2, 4, and 8 weeks after injection on the 1 U BTX‐treated side (P < 0.05). The mean absolute value of the red area of VISIA was ‐19.12 ± 51.91 on 1 U BTX‐treated side and 2.5 ± 42.08, on 0.5 UBTX‐treated side at 4 weeks after treatment, showing significant improvement on the 1 U side (P < 0.05). GAIS and DLQI were also significantly improved from Week 4 to Week 12 and Week 2 to Week 12, respectively (P < 0.05). There was no recurrence of symptoms with either 0.5 U or 1 U injection by 12 weeks. Apart from one patient who experienced facial tightness and three patients who had temporary aggravation of erythema, all of which resolved without treatment, 22 patients did not report any side effects except for injection pain during the procedure. Conclusions. BTX‐A can significantly improves symptoms and quality of life in patients with refractory rosacea with few side effects. A single‐point injection of 1 U was more effective. This trial is registered with NCT06282679.

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.

Risk Factors for Intraoperative Instability in Sedated Patients Undergoing Pulmonary Vein Isolation Ablation.

Persistent or paroxysmal atrial fibrillation is typically treated with pulmonary vein isolation (PVI) ablation under deep sedation with propofol. Intraoperative hemodynamic or respiratory instability often interferes with the surgical procedure. We retrospectively investigated risk factors in 80 patients who underwent their first PVI ablation for atrial fibrillation at our hospital. Background and echocardiography findings were collected from their electronic charts and the questionnaires they completed during hospitalization. Total intraoperative propofol dose and bolus injections (total number and volume) were defined as surrogate measures of patient instability. Single and stepwise multiple regression were performed using each measure as the dependent variable. When total propofol dose was employed as the dependent variable, significant associations were observed with drinking status (P < 0.05) and body mass index (BMI) (P < 0.05). When total number or volume of intravenous propofol boluses were each used as the dependent variable, significant associations were noted with age (P < 0.05) and BMI (P < 0.05). Separately, statistical analyses were conducted using total propofol dose or total number of bolus injections as the dependent variable and echocardiography parameters as independent variables. A significant association was detected between total dose and left atrial dimension (P < 0.05). These results suggested that younger age, higher BMI (obesity), and current drinking status adversely affect patient stability under deep sedation. To ensure safe ablation, physicians should pay attention to these risk factors when administering deep sedation for PVI.

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 &lt; 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.