Effects Of Long-term Use Research Articles

HPMC Extended-Release Multi-Composite Matrix for Co-delivery of Oxcarbamazepine and Vitamin D.

Background: Carbamazepine (CBZ) is considered as first-line treatment for epilepsy. The literature has signified a history of non-uniform drug performance and clinical failures. However, many studies suggested that Oxcarbazepine (OXC), a structural analog of CBZ, may have an equivalent antiepileptic effect. OXC follows a different metabolic pathway other than CBZ. However, both share the same mechanism of action by blocking voltage-gated sodium channels. Objectives: This study aimed to form hydroxypropyl methylcellulose (HPMC) extended-release tablets containing OXC combined with vitamin D. Methods: These formulated tablets were tested for their dissolution rate, tablet hardness, friability, thickness and pharmacokinetic parameters (Cmax and Cmin). Blood sodium levels were additionally investigated to ensure the absence of hyponatremia; the main side effect of long-term use of CBZ and some of its derivatives. Results: The use of HPMC inhibited the formation of dihydrate OXC form thus offering a significant extended-release profile. OXC also showed a highlighted capability to attain high bioavailability. Microcrystalline cellulose (MCC) was also added to tablets formed to inhibit polymorphic transformation. Tablets containing OXC co-delivered with vitamin D ensured significantly decreased susceptibility to hyponatremia, and an extended-release profile was evident. Lower amounts of OXC were loaded in formed tablets containing vitamin D owing to the synergistic effect between vitamin D and antiepileptic drugs. Conclusion: Conclusively, employing these newly HPMC-constructed tablets of OXC co-delivered with vitamin D appeared to be a promising option for the effective management of epilepsy with least side effects.

Effective synthesis of fluorescent carbon dots and their application in controllable detection of deferasirox

As an iron chelation therapy, deferasirox (DEF) is commonly used as the primary treatment drug to prevent intracellular iron overload in patients with thalassemia who require long-term and large blood transfusions. However, due to the toxic side effects of long-term use, building a convenient and sensitive DEF detection method remains an important task. This study developed a simple and effective fluorescence detection strategy for DEF based on the coordination effect of DEF and Cu2+ (DEF-Cu). The high quantum yield N-doped blue emission carbon dots (CDs) synthesized by a simple one-step hydrothermal method were applied as the fluorescent probe. The DEF-Cu exhibited a new absorption peak centered at 334 nm, overlapping with the absorption wavelength of CDs, resulting in an internal filtration effect (IFE) for quenching the fluorescence of CDs. The quenching degrees of CDs caused by DEF-Cu showed a good linear relationship in the range of 0.5–20 μg/mL, with a detection limit (LOD) as low as 0.12 μg/mL. The accurate detections of DEF in dispersible tablets and plasma were also achieved. This strategy not only enriched the understanding of the properties of target drugs but also provided valuable insights for designing CDs with specific luminescent properties and applying them to distinctive methods for drug analysis.

Effect of Long-Term Inhaled Corticosteroid Therapy on Metabolic And Anthropometric Parameters in Pediatric Patients with Asthma

Background: The long-term impact of inhaled corticosteroids (ICSs) metabolic parameters of asthmatic children is still uncertain. Objective: This study aimed to evaluate the effects of long-term use of ICSs on metabolic and anthropometric measures in children with asthma in Iran. Methods: This case-control study was conducted among 200 pediatric asthmatic patients who were referred to Abuzar Hospital (Ahvaz, Iran) during nine months. Demographic and clinical data of the patients were recorded. The participants were categorized into two groups: Group 1 (n = 100) comprising children with moderate to severe asthma, and Group 2 (n = 100) consisting of those with mild asthma. Results: The average age of 200 patients was 8.1 ± 2.9 years. The majority of them were male. The prevalence of wasting, stunting, obesity, and overweight was higher among Group 1 compared to Group 2 (p < 0.05). Patients in Group 1 had significantly higher levels of calcium, vitamin D, lipids, and glycemic parameters than those in Group 2 (p < 0.05). In addition, the duration of ICS use was notably longer in Group 1 (p < 0.05). Conclusion: Children with moderate and severe asthma had significantly elevated lipid and glycemic parameters, as well as a higher prevalence of wasting, stunting, obesity, and overweight compared to patients with mild asthma. Further studies involving larger sample sizes and longer durations are necessary to confirm these findings.

Pediatric Chronic Inflammatory Demyelinating Polyneuropathy: Challenges in Diagnosis andTherapeutic Strategies.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neurological disorder seen in both pediatric and adult populations. CIDP typically presents with progressive and persistent weakness over at least 4 weeks in addition to sensory symptoms in the extremities. Although CIDP shares common clinical features between children and adults, it sometimes presents as a distinct clinical entity in children that requires close attention and recognition. A major caveat when diagnosing a child with CIDP is the clinical and diagnostic overlap with inherited neuropathies, most commonly Charcot-Marie-Tooth disease (CMT). Demyelinating CMT (dCMT) and CIDP might share similar clinical presentations, and sometimes it might be difficult to differentiate them on the basis of the electrodiagnostic findings or cerebrospinal fluid (CSF) albumino-cytological dissociation. This indeed merits early consideration for genetic testing in patients who do not respond to conventional CIDP therapies. Current treatment options for CIDP include intravenous immunoglobulins (IVIG), corticosteroids (CS), and plasmapheresis (PLEX). The need for novel therapies is essential in instances where patients continue to have symptoms despite the standard therapies or due to adverse effects of long-term use of standard therapies such as CS. This paper reviews the challenges in the diagnosis of CIDP in children and the current as well as novel therapies for CIDP.

The effects of long-term application of fomesafen on weed seedbank and resistance levels of Amaranthus retroflexus L.

Amaranthus retroflexus L. is one of the invasive malignant weeds in soybean fields. Diphenyl ether herbicides are commonly used to control weeds in soybean fields currently, among which fomesafen is the most widely used. With the long-term use of fomesafen, the weed species in soybean fields in multiple areas declined, and the control effect of fomesafen against Amaranthus retroflexus decreased significantly. This study aims to confirm the effects of long-term use of fomesafen on weed community richness and the current resistance level of Amaranthus retroflexus. In this paper, the result of seed germination indicated that the weed community richness decreased significantly due to the long-term application of fomesafen, and the primary dominant weed was Amaranthus retroflexus. The result of the whole-plant bioassay showed that Amaranthus retroflexus has developed resistance to fomesafen, and the resistance index was 50~59 g a.i. ha-1. The resistance level and mechanism of Amaranthus retroflexus were clarified by target gene detection, enzyme activity determination, and gene expression analysis. The results showed that there were both target resistance with Arg128Gly mutation in the PPX2 gene and non-target resistance (NTSR), with increased activity of metabolic enzymes (cytochromes P450 (P450s) and glutathione S-transferase (GSTs)) and protective enzymes (peroxidase (POD) and catalase (CAT)) in Amaranthus retroflexus.

Randomized Comparison of Progression of Atherosclerotic Plaques and Calcification of Coronary Artery in Atrial Fibrillation Patients Treated With Edoxaban Versus Warfarin (The REPRESENT-AF trial)

Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.

Effect of Long-Term Use of Nitrogen, Phosphorus, and Potassium Fertilizers on the Contents of Phosphorus Compounds in Soddy-Podzolic Soil of the Urals

Effect of Long-Term Use of Nitrogen, Phosphorus, and Potassium Fertilizers on the Contents of Phosphorus Compounds in Soddy-Podzolic Soil of the Urals

Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice

Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.

Gene expression in the dorsal root ganglion and the cerebrospinal fluid metabolome in polyneuropathy and opioid tolerance in rats

First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. Csf3r and Fkbp5). Some, e.g. Alox15 and Slc12a5, were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.

#1755 Cardio-protective effect of soy proteins during long-term consumption of Cynomolgus Monkeys high-saline diet

Abstract Background and Aims High salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Recently, it has been found that the introduction of soy protein into the diet can have some nephroprotective and cardioprotective effects in chronic kidney disease. Considering the cardioprotective effect of soy proteins in chronic kidney disease, the question arose about the possibility of using soy proteins to neutralize the damaging effect of a high-salt diet on the cardiovascular system. This work aims to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling in monkeys. Method The study was performed on male Macaca fascicularis. The animals were divided into three groups (6 animals each), comparable in weight and age (6-8 years, body weight - 5.15-9.7 kg). The control group received a standard diet (2 g NaCl/kg feed). The second was a high salt diet (8 g NaCl/kg feed), and the third was a high salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography (EchoCG), registration of BP and heart rate were performed at baseline, after 4 and 12 months. EchoCG was performed with a sector transducer with a frequency of 3–5 MHz on the Chison SonoTouch 60 ultrasound system (China). EchoCG was performed in B_mode (two-dimensional scanning), M_mode (one-dimensional scanning), as well as in pulse and tissue Doppler modes. Statistical analysis was performed using parametric statistics: mixed ANOVA in comparing data from 3 study groups (with post hoc analysis using Tukey criterion) and single factor variance analysis for related samples in studying the dynamics of one or another index in each group during the 12-month follow-up. Differences were considered significant at p < 0.05. Results In animals of all three groups for 12 months, blood pressure (BPsis-109±10.09, BPdias – 60 ± 7.42 mm Hg) and heart rate (77 ± 12.61 min-1) did not change significantly (p>0. 05). However, in macaques on a high-salt diet, deterioration in left ventricular (LV) systolic and diastolic function was noted by the end of the study. Macaques of this group had a decrease in the LV shortening fraction (27.9±2.69%) and an increase in the thickness of the posterior wall of the LV in systole (0.69±0.039 cm), LV mass (19.60±2.83 g), compared with animals additionally receiving soy proteins (34.9±6.57%; 0.57 0.0559 cm; 14.86±2.94 g, respectively; all p < 0.05). In addition, the monkeys receiving soy isolate did not differ from the control in these parameters. By the time the study was completed, the animals in this group had significantly increased the magnitude of systolic excursion of the mitral annulus plane, and signs of improvement in LV diastolic function appeared in the form of an increase in the maximum rate of excursion of the mitral valve fibrous annulus in early diastole, as well as a decrease in the E/e' ratio. The thickness of the interventricular septum also decreased (0.42±0.04 cm; in the high-salt group - 0.51±0.08 cm), which can be interpreted as a sign of positive myocardial remodeling. Conclusion Thus, high salt intake leads to adverse structural and functional disorders of the heart in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

Side effects of proton pump inhibitors with long-term use: focus on the urinary system

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the associations between PPIs and a number of diseases/conditions. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to January 30, 2024. In this review, we examined the effect of long-term use of PPIs on the urinary system. This review demonstrates possible changes in the urinary system and an increased risk of developing nephrolithiasis, acute interstitial nephritis, acute kidney injury, chronic kidney disease, end-stage renal failure with long-term use of PPIs, which should certainly be taken into account when prescribing them for a long period, especially in patients with comorbid pathology.

Highly sensitive and label-free detection of naproxen using mixed metal oxide-based field effect transistor as a biosensor for in-vitro analysis of urine

Naproxen (Nap) is a nonsteroidal anti-inflammatory drug widely prescribed for treating fever, inflammation, and pain due to its easy absorption. Considering the side effects of long-term use of Nap and the risk of environmental pollution as a precursor, it is necessary to measure its concentration. ISFET-based sensors are very attractive tools for monitoring small amounts of analytes in biological samples. On the other hand, stabilizing nanocomposites with Nap oxidation capability provides an electrochemical signal for quantification. In this study, ISFET was used for comparative analysis of Nap concentration employing CeO2/CuO/MnO, CeO2/CuO/NiO multi-metal oxides, and La-doped CoFe layered double hydroxide (LDH) as sensing layers for the first time. The detection limits of the mentioned layers were 14.08 μM, 11.15 μM, and 19.11 μM, respectively, and the method was used to detect Nap in urine with a linear range of 0–400 μM. Compared to other methods, the proposed ISFET-based sensor for Nap detection has the capability of miniaturization, low sample amount, real-time measurement, low electrical power requirement, reusability, and high stability.

Efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease: A protocol for meta-analysis and systematic review.

The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment.

A narrative review on rebound acid hypersecretion due to long-term use of proton pump inhibitors

Objectives Proton pump inhibitors (PPIs) are the most commonly used drugs to reduce hyperacidity. The usage of PPIs reduces the secretion of gastric juice; their prolonged usage results in gastric acid suppression with hypergastrinemia while their stoppage results in hypersecretion of gastric juice. This kind of paradoxical reaction is seen in the rebound effect of drugs. Dr. Samuel Hahnemann gave us the vital principles of homeopathy, the law of similitude, i.e., “similia similibus curentur” derived from the “Nature’s Law of Cure”. This also tells us that the primary action of medicine stimulates the dynamic expression of an organism (vital force), which results in the counteraction called secondary action by the organism. Material and Methods Review of literature on the effects of long-term use of PPIs and rebound hypersecretion of gastric juice due to PPIs. Results For this review article, 16 most relevant articles are selected from the search results. Thirteen systematic reviews, two randomized control trials, and one pilot study are included. Rebound acid hypersecretion (RAHS) occurs after prolonged treatment with histamine-2 blockers and PPIs, causing gastric hypoacidity and hypergastrinemia. Longer PPI durations can result in prolonged hypersecretion, with moderate hypergastrinemia and increased enterochromaffin-like (ECL) cell hyperplasia. Deprescribing PPIs is crucial to reduce RAHS and safety concerns. Long-term usage can lead to nutritional deficiencies, respiratory infections, and bone fractures. Conclusion Homeopathic remedies have shown significant results in treating symptoms caused due to gastritis, ulcers, gastroesophageal reflux disease, etc., and further research is needed to reduce RAHS caused due to the long-term use of PPIs.

IJCM_352A: Effects of usage of Portable Listening Devices among Medical Students of SBKS MIRC Sumandeep Vidyapeeth

Background: Over 1 billion young people globally are at risk of hearing loss and road traffic accidents due to unsafe listening practices while using portable listening devices (PLDs). Rapid proliferation of mobile phones with built-in music playback facility has rendered nearly universal PLD access. Objective: 1. To find prevalence of usage of PLD among the medical students. 2. To make students aware about the various harmful effects of long term use of PLD Methodology: A Cross sectional study was conducted among students of 2nd, 3rd year part 1 and 3rd year part 2 MBBS of SBKS MI RC Sumandeep Vidyapeeth. After obtaining permission from ethics committee data was collected with the help of pre tested, pre formed questionnaire. Results: Study demonstrates the usage of portable listening devices among 380 medical students. The average number of days with PLD usage in a typical week was reported nearly equal in both male and female students. Nearly two-third (61.31%) of the students restricting listening to music on their PLDs on a typical day to1-3hrs, while more than one-fourth (32.89%) listened between 3-7 hrs. However, 22 (5.8%) students reported time spent listening to music on their PLD exceeding 7hrs daily. Self-reported hearing loss and ringing in ears (tinnitus) which persisted for at least 3 days within the previous 6 months were reported by 173 students in total. Conclusion: The probable association between long-term PLD usage and the risks of developing hearing loss and ringing in ears was considered to be unlikely by students. Significantly higher proportion of male compared to female students did not perceive any risks associated with PLD use.

Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a “postmortem” analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

Лекарственная безопасность: в фокусе долгосрочная терапия ингибиторами протонной помпы. Возможный сердечно-сосудистый риск и редкие побочные эффекты

Proton pump inhibitors are the most effective drugs for the treatment of acid-related diseases. In recent decades, the use of PPIs has increased exponentially. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. There are no reviews in the domestic literature on the safety of PPIs during long-term use. In this regard, a search was conducted in the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to November 15, 2023, which showed that long-term use of PPIs is associated with the possible development of numerous side effects. The first publications examined the likely side effects of long-term use of PPIs: the development of infections, increased risk of fractures and kidney pathology, and possible side effects: the risk of cancer and electrolyte disturbances. This review examines the possible cardiovascular risk of long-term PPI use and a number of rare side effects, many of which have been described in recent years. The key to mitigating side effects is judicious use of PPIs at the lowest effective dose and as quickly as possible. If there are clear indications for long-term PPI use, monitoring should be carried out to identify side effects.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of β-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

An empirical evaluation of approximate and exact regression-based causal mediation approaches for a binary outcome and a continuous or a binary mediator for case-control study designs

BackgroundIn the causal mediation analysis framework, several parametric regression-based approaches have been introduced in past years for decomposing the total effect of an exposure on a binary outcome into a direct effect and an indirect effect through a target mediator. In this context, a well-known strategy involves specifying a logistic model for the outcome and invoking the rare outcome assumption (ROA) to simplify estimation. Recently, exact estimators for natural direct and indirect effects have been introduced to circumvent the challenges prompted by the ROA. As for the approximate approaches relying on the ROA, these exact approaches cannot be used as is on case-control data where the sampling mechanism depends on the outcome.MethodsConsidering a continuous or a binary mediator, we empirically compare the approximate and exact approaches using simulated data under various case-control scenarios. An illustration of these approaches on case-control data is provided, where the natural mediation effects of long-term use of oral contraceptives on ovarian cancer, with lifetime number of ovulatory cycles as the mediator, are estimated.ResultsIn the simulations, we found few differences between the performances of the approximate and exact approaches when the outcome was rare, both marginally and conditionally on variables. However, the performance of the approximate approaches degraded as the prevalence of the outcome increased in at least one stratum of variables. Differences in behavior were also observed among the approximate approaches. In the data analysis, all studied approaches were in agreement with respect to the natural direct and indirect effects estimates.ConclusionsIn the case where a violation of the ROA applies or is expected, approximate mediation approaches should be avoided or used with caution, and exact estimators favored.

Safety assessment of Acori Tatarinowii Rhizoma: acute and subacute oral toxicity.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000mg/kg of the ATR extract for 28days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.