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BMJ Case Reports Mar 2024Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same...
Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same patient. These two possibilities must be distinguished in patients with multiorgan involvement to ensure early diagnosis and treatment. Here, we report a case of a previously healthy man who presented with simultaneous Takayasu arteritis and Crohn's disease. He presented with heart failure with reduced ejection fraction and severe aortic regurgitation. An echocardiogram demonstrated a greatly dilated aorta, and a diagnosis of Takayasu arteritis was made, confirmed with CT aortogram. Inpatient treatment was begun, but the patient subsequently developed bloody diarrhoea a few days after admission. Colonoscopy done to locate the source of bleeding showed colonic ulcers; a biopsy confirmed a diagnosis of Crohn's disease. The patient was successfully managed with medical management of heart failure, steroids, mesalamine and azathioprine, and has been in remission for the last 2 years.
Topics: Male; Middle Aged; Humans; Crohn Disease; Takayasu Arteritis; Azathioprine; Heart Failure; Autoimmune Diseases
PubMed: 38531553
DOI: 10.1136/bcr-2023-259110 -
Digestion 20245-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often...
Analysis of the Medication Persistence Rate for and Adherence to Oral 5-Aminosalicylic Acid Preparations in Japanese Patients with Ulcerative Colitis: Study Using a Nationwide Claims Database.
INTRODUCTION
5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date.
METHODS
Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population.
RESULTS
An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151-180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151-180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations.
CONCLUSION
The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations.
Topics: Humans; Colitis, Ulcerative; Mesalamine; Medication Adherence; Male; Female; Administration, Oral; Middle Aged; Adult; Japan; Anti-Inflammatory Agents, Non-Steroidal; Databases, Factual; Aged; Delayed-Action Preparations; Retrospective Studies; Young Adult; Administration, Topical; East Asian People
PubMed: 38527451
DOI: 10.1159/000538319 -
Advanced Biomedical Research 2024Ulcerative colitis (UC) is one of the inflammatory gastrointestinal diseases. It causes irritation, inflammation, and ulcers in the digestive tract. UC is distinguished...
BACKGROUND
Ulcerative colitis (UC) is one of the inflammatory gastrointestinal diseases. It causes irritation, inflammation, and ulcers in the digestive tract. UC is distinguished clinically by abdominal and rectal pain and intestinal secretion abnormalities. Mesenchymal stem cell (MSC) therapy could be the underlying treatment for UC. This study aimed to compare the results of MSC therapy with tretinoin and caffeine in an animal model.
MATERIALS AND METHODS
Sixty male BALB/c mice were randomly divided into six equal groups. Five groups were exposed to acetic acid-induced colitis, and one healthy negative control group was designed. The positive control group was UC-induced mouse model with no treatment. Besides, treatment groups were MSCs (n = 2×10) that received tretinoin and caffeine. The treatment group was given mesalazine orally. The decision to begin treatment was taken after monitoring the symptoms of the UC.
RESULTS
MSCs, tretinoin, and caffeine-treated MSCs significantly decrease inflammatory cytokines (interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α) and inflammatory mediators (myeloperoxidase (MPO) and nitric oxide (NO)) compared with the positive control group. However, the alleviated effects of tretinoin-treated MSCs significantly were more than those of MSCs and caffeine-treated MSCs.
CONCLUSION
MSC therapy is an effective option for UC and can prevent disease progression. The results represented a high developmental rate and simple cell application of MSC therapy in UC patients. Also, MSC therapy's ability for immunomodulation is strengthened by drugs that improve their microenvironment by binding to their receptors.
PubMed: 38525396
DOI: 10.4103/abr.abr_173_23 -
Die Pharmazie Feb 2024Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although...
Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although the use of titanium oxide nanoparticles is regulated, their safety has not been established. Furthermore, the interaction between titanium oxide nanoparticles and various chemical substances and pharmaceuticals is unknown. We co-administered rutile-type titanium oxide nanoparticles (nTR) or anatase-type titanium oxide nanoparticles (nTA) to mice together with paraquat (PQ), cisplatin (CDDP), or anti-5-aminosalicylic acid (5-ASA), and investigated the extent, if any, of liver and kidney injury. As a result, when nTA and nTR were administered alone, no increases were observed in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are indicators of liver damage, or urea nitrogen (BUN), which is an indicator of kidney damage. Next, nTA and nTR were co-administered with PQ, CDDP or 5-ASA. Although no increase in ALT or AST was observed, BUN levels increased significantly and acute kidney injury was induced. The findings suggested that titanium oxide nanoparticles induce acute kidney injury through their interaction with chemicals and drugs.
Topics: Mice; Animals; Cisplatin; Paraquat; Mesalamine; Nanoparticles; Acute Kidney Injury; Titanium
PubMed: 38509631
DOI: 10.1691/ph.2024.3655 -
Journal of Translational Medicine Mar 2024Osteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is... (Meta-Analysis)
Meta-Analysis
Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions.
BACKGROUND
Osteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is due to a combination of factors, although the pivotal mechanisms underlying the disease are still obscure. Moreover, current treatments are still poorly effective, and patients experience a painful and degenerative disease course.
METHODS
We used an integrative approach that led us to extract a consensus signature from a meta-analysis of three different OA cohorts. We performed a network-based drug prioritization to detect the most relevant drugs targeting these genes and validated in vitro the most promising candidates. We also proposed a risk score based on a minimal set of genes to predict the OA clinical stage from RNA-Seq data.
RESULTS
We derived a consensus signature of 44 genes that we validated on an independent dataset. Using network analysis, we identified Resveratrol, Tenoxicam, Benzbromarone, Pirinixic Acid, and Mesalazine as putative drugs of interest for therapeutics in OA for anti-inflammatory properties. We also derived a list of seven gene-targets validated with functional RT-qPCR assays, confirming the in silico predictions. Finally, we identified a predictive subset of genes composed of DNER, TNFSF11, THBS3, LOXL3, TSPAN2, DYSF, ASPN and HTRA1 to compute the patient's risk score. We validated this risk score on an independent dataset with a high AUC (0.875) and compared it with the same approach computed using the entire consensus signature (AUC 0.922).
CONCLUSIONS
The consensus signature highlights crucial mechanisms for disease progression. Moreover, these genes were associated with several candidate drugs that could represent potential innovative therapeutics. Furthermore, the patient's risk scores can be used in clinical settings.
Topics: Middle Aged; Humans; Osteoarthritis
PubMed: 38491514
DOI: 10.1186/s12967-024-05006-z -
AAPS PharmSciTech Mar 2024Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse...
Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.
Topics: Mesalamine; Bifidobacterium bifidum; Hydrogels; Colon; Anti-Inflammatory Agents; Polymethacrylic Acids
PubMed: 38485901
DOI: 10.1208/s12249-024-02764-3 -
Deutsche Medizinische Wochenschrift... Mar 2024Acute abdominal pain may relate to specific organ systems and needs an interdisciplinary approach with close collaboration between internal and surgical disciplines....
Acute abdominal pain may relate to specific organ systems and needs an interdisciplinary approach with close collaboration between internal and surgical disciplines. Main objective is to shorten the diagnostic work-up between the beginning of the symptoms and their therapy. After clarifying of the five w-questions: when, how, how long, why, and where, abdominal ultrasound, ECG, laboratory diagnostics and early application of computed tomography should be performed.For the most part, chronic abdominal pain is caused by disorders of the gut-brain-axis such as the irritable bowel syndrome. Because of the synaptic plasticity, the processing of pain is dynamic and cannot be related to a single organ system. This problem is obvious in patients with irritable bowel syndrome and colonic diverticula, which may be interpreted as symptomatic uncomplicated diverticular disease (SUDD, type 3a). However, a reliable clinical differentiation between both groups is not possible. The establishment of SUDD (type 3a) considerable widened the application area of mesalazine.
Topics: Humans; Irritable Bowel Syndrome; Diverticular Diseases; Diverticulosis, Colonic; Mesalamine; Abdominal Pain
PubMed: 38479421
DOI: 10.1055/a-2063-0967 -
International Journal of Molecular... Feb 2024Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity...
Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.
Topics: Humans; Mesalamine; Tumor Necrosis Factor-alpha; Cells, Cultured; Sinusitis; Nasal Mucosa; Interleukin-6; Anti-Inflammatory Agents; Chronic Disease; Epithelial Cells
PubMed: 38474043
DOI: 10.3390/ijms25052796 -
Oral and Maxillofacial Surgery Mar 2024Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel...
BACKGROUND
Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV).
PURPOSE
To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis.
METHODS
An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD.
RESULTS/CONCLUSIONS
Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted.
PubMed: 38467949
DOI: 10.1007/s10006-024-01234-1 -
Functional & Integrative Genomics Mar 2024Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated...
Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.
Topics: Mice; Animals; Scutellaria baicalensis; Mesalamine; NLR Family, Pyrin Domain-Containing 3 Protein; Colitis; Carcinogenesis; Mice, Inbred C57BL
PubMed: 38467948
DOI: 10.1007/s10142-024-01334-x