Gastrointestinal Side Effects Research Articles

Review on recent advancements in understanding acetylsalicylic acid-induced gastrointestinal injury: mechanisms, medication, and dosage refinement.

Acetylsalicylic acid (ASA) is a clinical drug with multiple effects, including prevention of cardiovascular adverse events and anti-cancer effects. However, gastrointestinal side effects, such as gastrointestinal ulcers and bleeding, limit the use of ASA and reduce patient compliance. Various studies have investigated the mechanisms of ASA-induced gastrointestinal injury, and many medicines have been reported to be effective in preventing and treating the adverse gastrointestinal effects of ASA. New formulations of ASA have demonstrated milder gastrointestinal injury than ASA alone. In this article, we summarized the mechanisms of ASA-induced gastrointestinal injury, drugs that resist gastrointestinal side effects of ASA, and progress in research on formulation improvement of ASA to help resolve the clinical dilemma of ASA usage.

FORMULATION AND CHARACTERISATION OF RISEDRONATE SODIUM SUBLINGUAL SPRAY

Objective: To formulate a propellant-free sublingual spray of Risedronate sodium, addressing issues of gastrointestinal side effects associated with current oral formulations and improving patient compliance. Methods: Initially, a fractional factorial design was used to screen variables, followed by a face-centered central composite design for optimization. Formulation batches were characterized by spray pattern, spray angle, leak test, prime test, drug delivery uniformity, drug content per spray, and ex-vivo permeation study. Results: The optimized batch O1 exhibited an ovality ratio of 1.1, a spray angle of 640, and a drug permeation percentage of 4. In vivo absorption analysis revealed that the relative bioavailability of optimized batch O1 was 2.27 times higher than that of the plain drug solution. Compatibility of the product pack with excipients and the drug was confirmed through stability studies of batch O1. Conclusion: The study concluded that Risedronate sodium sublingual spray presents a promising alternative to oral administration, potentially reducing gastrointestinal side effects and enhancing patient compliance.

Lefamulin for Mycoplasma genitalium treatment failure in Australia and the USA: a case series and pilot open-label parallel arm randomised trial

ObjectivesMycoplasma genitalium (MG) causes urethritis and is associated with cervicitis, pelvic inflammatory disease and preterm delivery. Antimicrobial resistance is widespread and cure rates are declining. Lefamulin, a novel pleuromutilin, may...

Abstract 4134308: Re-evaluating the safety profile of Semaglutide: An updated meta-analysis

Background: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. Methods: Randomized controlled trials assessing the safety of semaglutide versus placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia and new-onset neoplasm. Results: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. (See Figure 1) Conclusion: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.

Unlocking the potential of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in revolutionizing type 2 diabetes management: A comprehensive review

Diabetes mellitus (DM) is a long-term metabolic disorder caused by inadequate production and resistance to insulin. The prevalence of DM is rapidly increasing, with type 2 diabetes (T2D) accounting for more than 90% of cases. Despite new treatments, many patients with T2D do not meet their glycemic targets due to clinical inertia. This review provides an overview of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the management of T2D. The review synthesizes data from clinical trials and meta-analyses on the efficacy, safety, and cost-effectiveness of GLP-1 RAs. It also discusses the mechanisms of action, classification, and barriers to adherence and persistence in therapy. GLP-1 RAs improve glycemic control by lowering A1C levels and promoting weight loss. They have cardioprotective effects and may reduce endothelial inflammation, oxidative stress, and blood pressure. Adherence to GLP-1 RAs is better with once-weekly injections, though gastrointestinal side effects and cost can affect persistence. Semaglutide and liraglutide have shown significant weight reduction, with semaglutide being particularly effective. GLP-1 RAs are cost-effective due to reduced healthcare costs associated with fewer hospitalizations and lower mortality rates. Safety concerns include gastrointestinal issues, pancreatitis, and rare cases of diabetic retinopathy and thyroid C-cell tumors. For clinical practice, GLP-1 RAs represent a valuable option not only for glycemic control but also for weight management and cardiovascular protection. Incorporating GLP-1 RAs into treatment plans can improve patient outcomes, and optimizing dosing regimens and addressing barriers such as cost and side effects are crucial to enhancing patient adherence and long-term treatment success.

PaedVacCOVID - safety of the BNT162b2 vaccine against the SARS-CoV-2 in children with and without comorbidities aged 5 to 11 years.

Little is known about specific safety aspects in children with significant comorbidities receiving the mRNA vaccine BNT162b2, as approval studies did not address this population. This study's purpose is to evaluate safety and adverse events in these children compared to healthy children. In this prospective, multicentre, industry-independent cohort study, caregivers whose children received BNT162b2 were asked to participate in an online questionnaire. Potential side effects were evaluated in ten organ related categories. Frequency of symptoms was compared in both cohorts by bivariate analysis. From a total of 1,294 responses to the questionnaire, 793 data sets were included into the analysis (179 children with comorbidities and 614 healthy children). Responses were given at a median of 17 days after vaccination. Overall, safety of BNT162b2 was high in both cohorts. Psychological (OR: 3.56, [95% CI: 1.461 to 8.629]), pulmonary (OR: 7.14, [95% CI: 2.039 to 21.48]), gastrointestinal (OR: 2.35, [95% CI: 1.231 to 4.665]), neurological (OR: 1.74, [95% CI: 1.078 to 2.796]) and dermatological (OR: 2.28, [95% CI: 1.220 to 4.172]) side effects were increased in children with comorbidities over healthy controls. The higher rate of reported post-vaccination symptoms could either be due to a higher susceptibility for symptomatic effects following immune stimulation, or due to a trained awareness to health-related symptoms. The data emphasizes the importance to evaluate safety of the new mRNA COVID-19 vaccines not only in healthy children but also in children with comorbidities. To perform such evaluation should be made mandatory for pharmaceutical enterprises.

Discovery of a Novel Macrocyclic Noncovalent CDK7 Inhibitor for Cancer Therapy.

Cyclin-dependent kinase 7 (CDK7) is a key regulator of the cell cycle and transcription, making it a promising target for cancer therapy. Although current CDK7 inhibitors have improved in their selectivity and druglike properties, CDK7 inhibitors have failed to progress through clinical development due to severe gastrointestinal and hematotoxic side effects. To mitigate these limitations, we have developed novel, macrocyclic, noncovalent CDK7 hit compounds 2 and 3 using a macrocyclization platform that has optimized these compounds from SY-5609, a leading clinical asset. We conducted extensive structure-activity relationship (SAR) studies to improve their potency, enhance oral bioavailability, and reduce intestinal distribution, which resulted in compound 13. Compound 13 exhibits potent in vitro activity, good ADME properties, and robust in vivo antitumor activity in xenograft models as a monotherapy. Notably, compound 13 with lower basicity demonstrated improved Caco-2 permeability, reduced blood/plasma ratio, and reduced intestinal distribution in rats, thus mitigating gastrointestinal and hematotoxic side effects.

Improving Diagnosis and Management of Opioid-Induced Constipation (OIC) in Clinical Practice: An Italian Expert Opinion

Opioid-induced constipation (OIC) is a very common and troublesome gastrointestinal side effect following the use of opioids. Despite existing international guidelines, OIC is largely underdiagnosed and undertreated. ECHO OIC is a European project designed to improve the diagnosis and management of OIC at the primary care level. The next phase of the ECHO OIC project is to review and adapt the proposed European pathway at national level, considering the local patient journey and clinical practice. A multidisciplinary group of 12 Italian experts reviewed and discussed the European path and formulated a seven-step guide for the practical management of OIC that is also easily applicable in primary care: 1. When prescribing long-term opioids, the physician should inform the patient of the possibility of the onset of OIC; 2. At opioid prescription, doctors should also prescribe a treatment for constipation, preferably macrogol or stimulant laxatives; 3. The patient should be evaluated for OIC within the second week of initiating opioid treatment, by clinical history and Rome IV criteria; 4. In the presence of constipation despite laxatives, prescription of a PAMORA (Peripherally Acting Mu Opioid Receptor Antagonist) should be considered; 5. When prescribing a PAMORA, prescribing information should be carefully reviewed, and patients should be accurately instructed for appropriate use; 6. Efficacy and tolerability of the PAMORA should be monitored regularly by Bowel Function Index, considering a cut-off of 30 for the possible step-up of OIC treatment; 7. After 4 weeks of treatment, if the efficacy of PAMORA is deemed inadequate, discontinuation of the PAMORA, addition of an anti-constipation drugs, change of opioid type, or referral to a specialist should be considered. Spreading knowledge about the OIC problem as much as possible to the health community is crucial to obtain not only an early treatment of the condition but also to promote its prevention.

Xiao-Ban-Xia Decoction Alleviates Chemotherapy-Induced Nausea and Vomiting by Inhibiting Ferroptosis via Activation of The Nrf2/SLC7A11/GPX4 Pathway.

Chemotherapy-induced nausea and vomiting (CINV) represents the common gastrointestinal side effect for cancer patients. Xiao-Ban-Xia decoction (XBXD), a classical anti-emetic traditional Chinese medicine formula, is frequently used for the clinical treatment of CINV. This study used a cisplatin-induced rat pica model to explore whether the anti-emetic mechanism of XBXD in treating CINV is related to ferroptosis. The inflammatory damage of the gastrointestinal tract is evaluated by HE staining and ELISA. The degree of ferroptosis are validated by the iron deposition, the levels of ROS, MDA, and GSH, and the ultrastructure of mitochondria in the gastric antrum and ileum. The potential ferroptosis-related targets of XBXD against CINV are screened by network pharmacology and further assessed by Western blot. XBXD significantly decreased the kaolin consumption in rats, and improved the inflammatory pathological damage, with decreased levels of HMGB1, IL-1β, and TNF-α. Furthermore, XBXD significantly suppressed ferroptosis, as indicated by the improvement of iron deposition, mitochondrial abnormalities, and oxidative stress. The network pharmacology and Western blot results indicated that XBXD activated the Nrf2/SLC7A11/GPX4 signaling pathway. This study proved that XBXD activates the Nrf2/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis, which represents a critical anti-emetic mechanism of XBXD in combatting CINV.

Oral sodium lactate ingestion does not increase blood lactate concentrations and is accompanied by moderate-to-severe gastrointestinal side effects.

Lactate has diverse roles in biology and has been implicated in the control of energy intake. A variety of methods (i.e., exercise, ingestion, and infusion) have been used to study its effects on different metabolic outcomes and the original intent of this project was to explore the effect of oral sodium lactate (Na-Lactate) ingestion on appetite regulation. During piloting, we were unable to show that Na-Lactate could increase blood lactate concentrations; thus, the purpose of this brief report is to highlight that oral Na-Lactate ingestion is not an effective method to study lactate metabolism. Five male participants (26 ± 3 yr, 82.4 ± 3.8 kg, 25.4 ± 1.6 kg·m-2) completed 15 experimental sessions where Na-Lactate solutions were consumed with the assessment of blood lactate preingestion, 30-min, 45-min, and 60-min postingestion. Oral Na-Lactate ingestion did not increase blood lactate concentrations (Pre: 0.9 ± 0.2; 30 min: 1.2 ± 0.7; 45 min: 1.0 ± 0.5; 60 min: 0.9 ± 0.4 mmol·L-1). In addition, there were moderate-to-severe gastrointestinal (GI) side effects (e.g., vomiting and diarrhea) following ingestion. Altogether, our data suggest that oral ingestion of Na-Lactate is not an effective method for studying lactate's role in metabolism as it did not increase blood lactate concentrations and was accompanied by problematic GI side effects.NEW & NOTEWORTHY Lactate has diverse roles in physiology, and a variety of methods have been used to explore its effects on metabolism. Here, we explored whether oral sodium lactate (Na-Lactate) ingestion could increase blood lactate concentrations. Oral Na-Lactate ingestion using a variety of dosing protocols did not increase blood lactate concentrations and was coupled with gastrointestinal issues. These results demonstrate that oral ingestion of Na-Lactate is not an effective method for studying lactate's role in metabolism.

Construction and Characterization of Thermosensitive Hydrogel Loaded with Donepezil Nanosuspension and its Application for Transnasal Delivery

AbstractDonepezil (DPZ) is a reversible cholinesterase inhibitor used to treat Alzheimer's disease (AD), while with disadvantages such as gastrointestinal side effects after oral administration and poor adherence in the elderly. The purpose of this study was to develop a thermosensitive hydrogels loaded with donepezil nanosuspension (DPZ‐NS‐gel) for transnasal administration to improve brain targeting and reduce peripheral toxicity. The results of powder X‐ray diffraction and differential scanning calorimeter showed that the crystal type of DPZ changed from form II to form C during the grinding process. DPZ‐NS‐gel was obtained by mixing DPZ‐NS into the blank thermosensitive hydrogel constructed with poloxamer 407 and poloxamer 188. DPZ‐NS‐gel was in sol state at 25 °C and formed gel at 33 °C. Compared with DPZ‐NS, the in vitro release of DPZ‐NS‐gel showed the sustained release profile. In vivo studies indicated that DPZ‐NS‐gel by nasal administration may increase the amount of drug entering into the brain. The in vivo safety evaluation showed no severe inflammatory response and pathological change when DPZ‐NS‐gel was administered by nasal administration. This study provided a promising strategy for clinical application in improving the bioavailability of DPZ in the brain, avoiding oral‐induced gastrointestinal side effects and improving medication adherence in the elderly.

Criteria for Re-Irradiation.

The treatment options for patients with progressive malignant tumors despite primary radiotherapy are often limited. In selected cases, re-irradiation can be offered. This article concerns the selection criteria and results of re-irradiation for certain types of cancer. This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to glioblastoma, head and neck tumors, and prostatic carcinoma. The published studies of re-irradiation are few in number and often of limited methodological quality. For glioblastoma, a randomized controlled trial (RCT) found that adding re-irradiation to treatment with bevacizumab yielded no significant improvement in either median progression-free survival or median overall survival (hazard ratio [HR] 0.73; p = 0.05 and HR 0.98; p = 0.46, respectively). Re-irradiation is a treatment option for locoregional recurrences of head and neck tumors after primary radiotherapy, but it carries a risk of serious side effects. For unresectable recurrences of nasopharyngeal carcinoma, an RCT has shown that hyperfractionated re-irradiation is more effective than normofractionated re-irradiation (overall survival: HR 0.54, p = 0.014). For locally recurrent prostatic carcinoma after radiotherapy, re-irradiation can yield good oncologic outcomes with an acceptable level of urogenital and gastrointestinal side effects (5-year recurrence-free survival: stereotactic body radiation therapy (SBRT), 58%; high dose rate (HDR) brachytherapy, 77%; versus salvage prostatectomy, 72%). RCTs on this topic are lacking. Re-irradiation is a treatment option for selected cancer patients. As the available scientific evidence is limited, multidisciplinary collaboration and participatory decision-making are particularly important.

Isotretinoin-associated chronic diarrhea as a complication of systemic isotretinoin therapy

Objective: Isotretinoin is a synthetic derivative of vitamin A that is highly effective in treating acne vulgaris. Although its common side effects include skin dryness, photosensitivity, epistaxis, and depressive disorders, gastrointestinal side effects should also be considered, though they are less frequently highlighted. Case: We aim to present a 28-year-old female patient who developed chronic diarrhea and associated hypokalemic paralysis during isotretinoin treatment, prescribed for acne management. This case underlines the importance of recognizing gastrointestinal side effects, alongside the more commonly known adverse effects of isotretinoin. Conclusion: Chronic diarrhea is a rare but significant side effect of isotretinoin that may lead to serious complications such as hypokalemic paralysis. In this case, we demonstrated how isotretinoin can cause metabolic imbalances, even in relatively healthy young adults, by inducing diarrhea. While the association between isotretinoin and inflammatory bowel disease remains inconclusive, clinicians should remain vigilant regarding the gastrointestinal side effects of isotretinoin. Early recognition and discontinuation of the drug, combined with appropriate supportive treatments, are essential in preventing further complications. Dermatologists and gastroenterologists should collaborate in identifying patients at higher risk, such as those with pre-existing gastrointestinal conditions, and closely monitor for any adverse effects during isotretinoin treatment. Future studies, particularly large-scale randomized controlled trials, are needed to better understand the relationship between isotretinoin and gastrointestinal side effects.

Formulation of Microemulsion-Based Gels for Enhanced Topical Administration of Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs are commonly administered orally to manage pain and inflammation, but they can have negative gastrointestinal side effects. Topical delivery is an alternative, and microemulsions (μEs) have been shown to be effective in facilitating, but they suffer from a liquid nature and low long-term retention on the skin. Hence, microemulsified gels (μEGs) have been developed, and in this study, we explored certain μEGs with diclofenac sodium (DF-Na) and naproxen sodium (NP-Na) with the hypothesis to ensure a slower and more sustained delivery of NSAIDs through the skin. The μEGs comprised castor oil (∼8%), water (∼12%), Tween-20 (∼72%), Span-20 (∼8%), poloxamer 407, and DF-Na or NP-Na. Optical microscopy was used to study the microstructures in the μEs and μEGs, and phase transitions from water-in-oil (w/o) to oil-in-water (o/w) with continuous networks were observed. Based on studies with dynamic light scattering and analyses of electron micrographs, it was observed that the μEs and μEGs loaded with DF-Na and NP-Na comprised monomodal nanodroplets. The average sizes of the droplets were (∼35 nm) and (∼60 nm) for the μEGs, without and with drugs. Fluorescence spectroscopy was used to ensure that the drugs were more likely to be present in the hydrophobic microenvironment of the formulations. Moreover, ex vivo permeation studies were conducted at pH values of 5.5 and 7.4 across rabbit skin. The release rates of DF-Na (>99 ± 1.5%, P < 0.07) and NP-Na (>89 ± 1.1%, P < 0.01) were slower for the μEGs within 8-10 h than for the μEs at the low pH, which is of relevance to the optimal pH of the skin. It was observed that μEGs with high viscosities are effective and may have potential for use in topical drug delivery applications.

Colchicine prevents post-ablation atrial fibrillation recurrence: a systematic review and meta-analysis

Abstract Background Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure with appreciable effectiveness; however, post-AF ablation recurrence is often observed. The pathophysiology behind this recurrence is often inflammation and oxidative stress triggered during the ablation procedure. Colchicine is a potent anti-inflammatory agent that has emerged as a promising therapeutic for preventing post-ablation AF recurrence; however, the data available on its efficacy are limited. Purpose This meta-analysis aimed to investigate the outcomes of post-ablation AF patients who received colchicine in the postoperative period. Methods A comprehensive literature search spanning major bibliographic databases was conducted to retrieve studies comparing outcomes in post-ablation AF patients who received colchicine versus those who did not. The outcomes of interest included AF recurrence, pericarditis, gastrointestinal side effects, and hospitalization. AF recurrence was determined with a 12-lead electrocardiogram and/or Holter monitoring. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were pooled from all studies using the DerSimonian and Laird random-effects model. Statistical significance was set at p ≤ 0.05. Results Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up [OR: 0.62; 95% CI: 0.48, 0.79; p=0.0001] but had higher gastrointestinal side effects [OR: 2.67; 95% CI: 1.00, 7.12; p=0.05]. There were no statistically significant differences in acute pericarditis [OR: 0.54; 95% CI: 0.27, 1.05; p=0.07] or hospitalization [OR: 1.03; 95% CI: 0.73, 1.45; p=0.87]. Conclusion Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects such as diarrhea and nausea. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in the prevention of AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.

Factors Affecting the Use of Probiotics during Antibiotic Therapy

Aim: To indicate the importance of the use of probiotics and the factors that influence the use of probiotics during antibiotic therapy. Introduction: Antibiotics are pharmacological agents selectively toxic to bacteria, but non-toxic or acceptably toxic to humans, prescribed and used in the treatment of bacterial infections. The most common gastrointestinal complication during antibiotics use is diarrhea. Probiotics are live microorganisms, bacteria and yeasts, which are used in the therapy of numerous conditions, especially in intestinal diseases. Methods: An anonymous survey of 207 patients from Bosnia and Herzegovina who used antibiotics and probiotics in the period from February 2023 to March 2024. Results: The results indicate that the use of antibiotics is frequent. About a third of the examined patients used the probiotic occasionally or not at all during the duration of the antibiotic therapy. About two thirds of the patients took the probiotic on their own initiative. A large part of the examined patients is familiar with the purpose of using probiotics. The price of probiotics plays a significant role in the application and length of use of probiotics. Discussion: Frequent use of antibiotics can increase the likelihood of gastrointestinal side effects, especially diarrhea. The use of probiotics is often shorter than the duration of antibiotic therapy. It’s use is often occasional, and on patients initiative, mostly because of the price of probiotics. Conclusion: The obtained results indicate that it is important to point out the purpose of the use of probiotics in addition to antibiotics to patients, and that a decrease in the price of probiotics would increase the length of use of probiotics.

Intestinal obstruction following antituberculosis therapy in a patient with pancreatic carcinoma and pulmonary tuberculosis: a case report

IntroductionIntestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare.Case presentationWe report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient’s symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction.ConclusionsThis case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects.

Alleviating rheumatoid arthritis with a photo-pharmacotherapeutic glycan-integrated nanogel complex for advanced percutaneous delivery

The prospective of percutaneous drug delivery (PDD) mechanisms to address the limitations of oral and injectable treatment for rheumatoid arthritis (RA) is increasing. These limitations encompass inadequate compliance among patients and acute gastrointestinal side effects. However, the skin’s intrinsic layer can frequently hinder the percutaneous dispersion of RA medications, thus mitigating the efficiency of drug delivery. To circumvent this constraint, we developed a strontium ranelate (SrR)-loaded alginate (ALG) phototherapeutic hydrogel to assess its effectiveness in combating RA. Our studies revealed that this SrR-loaded ALG hydrogel incorporating photoelectrically responsive molybdenum disulfide nanoflowers (MoS2 NFs) and photothermally responsive polypyrrole nanoparticles (Ppy NPs) to form ALG@SrR-MoS2 NFs-Ppy NPs demonstrated substantial mechanical strength, potentially enabling delivery of hydrophilic therapeutic agents into the skin and significantly impeding the progression of RA. Comprehensive biochemical, histological, behavioral, and radiographic analyses in an animal model of zymosan-induced RA demonstrated that the application of these phototherapeutic ALG@SrR-MoS2 NFs-Ppy NPs effectively reduced inflammation, increased the presence of heat shock proteins, regulatory cluster of differentiation M2 macrophages, and alleviated joint degeneration associated with RA. As demonstrated by our findings, treating RA and possibly other autoimmune disorders with this phototherapeutic hydrogel system offers a distinctive, highly compliant, and therapeutically efficient method.

Anti-inflammatory and antioxidative effects of essential oil of Hyptis crenata on the intestinal injuries induced by methotrexate

Methotrexate (MTX) is an important drug for the treatment of cancer and other diseases. However, it induces many gastrointestinal inflammation-related side effects. The essential oil of Hyptis crenata (EOHc) has gastrointestinal protective and anti-inflammatory properties. Therefore, we aimed to investigate the effect of EOHc on MTX-induced intestinal inflammation in rats. Male Wistar rats were administered MTX or Saline for 3 days and EOHc (300 mg/kg) or vehicle for an additional 3 or 7 days. Half of the animal was euthanized 3 days after the end of MTX treatment (inflammation phase) and the remaining half euthanized 4 days later (post-inflammation phase). The MPO levels in the mucositis inflammation-related phase of the MTX-treated group were 284 % of the control in the duodenum (cont: 50,9 ± 9,97 U/mg of protein) and 231 % of the control in the ileum (cont: 30,4 ± 6,60 U/mg of protein). In the EOHc group, the levels were 50 % of control in the duodenum and 113 % in the ileum. During this phase, EOHc prevented the increase in TBARs levels and the decrease in thiol levels in the duodenum and jejunum. In the post-inflammation phase of mucositis, EOHc prevented the gastrointestinal transit alteration and, in general, increased food and water consumption. In conclusion, the observed effects, particularly the anti-inflammatory and antioxidant effects of EOHc, as well as its previously reported low toxicity, position EOHc as a promising candidate for reducing gastrointestinal side effects associated with the use of MTX.

Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis

ObjectiveCaffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic...