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International Journal of Molecular... May 2024Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid... (Meta-Analysis)
Meta-Analysis Review
The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.
Topics: Humans; Inflammatory Bowel Diseases; Psoriasis; Polymorphism, Single Nucleotide; Biological Products; Arthritis, Rheumatoid; Arthritis, Psoriatic; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88
PubMed: 38891983
DOI: 10.3390/ijms25115793 -
Foods (Basel, Switzerland) May 2024Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a... (Review)
Review
Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.
PubMed: 38890858
DOI: 10.3390/foods13111629 -
The Journal of Headache and Pain Jun 2024Large conductance calcium-activated potassium (BK) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Large conductance calcium-activated potassium (BK) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK channel opener) could induce migraine-like headache in persons with PPTH.
METHODS
This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.
RESULTS
Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).
CONCLUSIONS
Our results indicate that BK channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BK channel blockers in managing PPTH.
GOV IDENTIFIER
NCT05378074.
Topics: Humans; Female; Male; Adult; Double-Blind Method; Cross-Over Studies; Post-Traumatic Headache; Migraine Disorders; Middle Aged; Brain Concussion; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Young Adult; Large-Conductance Calcium-Activated Potassium Channels
PubMed: 38890563
DOI: 10.1186/s10194-024-01808-0 -
Scientific Reports Jun 2024Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents...
Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2-4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14-0.86, P = 0.02 for all cycles; 0.26, 0.11-0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.
Topics: Humans; Docetaxel; Dexamethasone; Female; Breast Neoplasms; Hand-Foot Syndrome; Middle Aged; Retrospective Studies; Aged; Adult; Dose-Response Relationship, Drug; Antineoplastic Agents
PubMed: 38890326
DOI: 10.1038/s41598-024-64553-z -
Biomedicine & Pharmacotherapy =... Jun 2024The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including...
The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including tabernanthalog (TBG), ibogainalog (IBG), and ibogaminalog (DM506), using mouse models of neuropathic (Chronic Constriction Injury; CCI) and visceral pain (dextrane sulfate sodium; DSS). Ibogalogs decreased mechanical hyperalgesia and allodynia induced by CCI in a dose- and timeframe-dependent manner, where IBG showed the longest anti-hyperalgesic activity at a comparatively lower dose, whereas DM506 displayed the quickest response. These compounds also decreased hypersensitivity induced by colitis, where DM506 showed the longest activity. To understand the mechanisms involved in these effects, two approaches were utilized: ibogalogs were challenged with the 5-HT receptor antagonist ketanserin and the pharmacological activity of these compounds was assessed at the respective 5-HT 5-HT, and 5-HT receptor subtypes. The behavioral results clearly demonstrated that ketanserin abolishes the pain-relieving activity of ibogalogs without inducing any effect per se, supporting the concept that 5-HT receptor activation, but not inhibition, is involved in this process. The functional results showed that ibogalogs potently activate the 5-HT and 5-HT receptor subtypes, whereas they behave as inverse agonists (except TBG) at the 5-HT receptor. Considering previous studies showing that 5-HT receptor inhibition, but not activation, and 5-HT receptor activation, but not inhibition, relieved chronic pain, we can discard these two receptor subtypes as participating in the pain-relieving activity of ibogalogs. The potential involvement of 5-HT receptor subtypes was also ruled out. In conclusion, the anti-hypersensitivity activity of ibogalogs in mice is mediated by a mechanism involving 5-HT receptor activation.
PubMed: 38889634
DOI: 10.1016/j.biopha.2024.116867 -
Journal of Investigational Allergology... Jun 2024
Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization.
Topics: Humans; Multiple Myeloma; Anaphylaxis; Mastocytosis, Systemic; Desensitization, Immunologic; Antibodies, Monoclonal, Humanized; Drug Hypersensitivity
PubMed: 38888584
DOI: 10.18176/jiaci.0990 -
Immunity, Inflammation and Disease Jun 2024For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the...
BACKGROUND
For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-β) derived from Trichinella spiralis, a crucial excretory product of this parasite.
OBJECTIVE
To explore the therapeutic potential of SUCLA-β in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation.
METHODS
In this research, we utilized the rTs-SUCLA-β protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs.
RESULTS
Treatment with rTs-SUCLA-β demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma.
CONCLUSIONS AND CLINICAL RELEVANCE
Our data revealed that T. spiralis-derived Ts-SUCLA-β protein may inhibit the allergic airway inflammation by regulating host immune responses.
Topics: Trichinella spiralis; Animals; Asthma; Mice; Ovalbumin; Helminth Proteins; Mice, Inbred BALB C; Disease Models, Animal; Female; Cytokines; Immunoglobulin E; Lung; T-Lymphocytes, Regulatory; Hypersensitivity; Th17 Cells
PubMed: 38888451
DOI: 10.1002/iid3.1321 -
Cancer Medicine Jun 2024Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL)...
BACKGROUND
Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL) are the same disease entity or two distinct diseases, patients with T-LBL often receive the same or similar treatment protocols as those with T-ALL.
METHODS
The outcomes of patients with or without L-asparaginase discontinuation were retrospectively analyzed among four national protocols: Japan Association of Childhood Leukemia Study (JACLS) ALL-02 and ALL-97 for T-ALL and Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 and JACLS NHL-98 for T-LBL. The hazard ratio (HR) was calculated with the Cox regression model by considering L-asparaginase discontinuation as a time-dependent variable.
RESULTS
In total, 199 patients with T-ALL, and 133 patients with T-LBL were included. L-asparaginase discontinuation compromised event-free survival (EFS) of T-ALL patients (ALL-02: HR 3.32, 95% confidence interval [CI] 1.40-7.90; ALL-97: HR 3.39, 95%CI 1.19-9.67). Conversely, EFS compromise was not detected among T-LBL patients (ALB-NHL03: HR 1.39, 95%CI 0.41-4.68; NHL-98: HR 0.92, 95%CI 0.11-7.60).
CONCLUSION
The effects of L-asparaginase discontinuation differed between T-ALL and T-LBL. We assume that the differential impact results from (1) the inherent differential response to L-asparaginase between them and/or (2) a less stringent assessment of early treatment response in T-LBL than in T-ALL. Given the poor salvage rate of refractory or relapsed T-ALL and T-LBL, optimization of the frontline therapy is critical, and the current study provides a new suggestion for further treatment modifications. However, larger studies in contemporary intensified treatment protocols are required.
Topics: Humans; Asparaginase; Child; Male; Female; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Child, Preschool; Retrospective Studies; Adolescent; Infant; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Japan; Antineoplastic Agents
PubMed: 38888368
DOI: 10.1002/cam4.7246 -
Investigative Ophthalmology & Visual... Jun 2024The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy...
PURPOSE
The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD).
METHODS
Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin.
RESULTS
All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome.
CONCLUSIONS
Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.
Topics: Humans; Male; Female; Adult; Microbiota; Dry Eye Syndromes; Eyelids; Stevens-Johnson Syndrome; Middle Aged; Young Adult; Bacteria; RNA, Ribosomal, 16S; DNA, Bacterial; Adolescent; Meibomian Glands; Meibomian Gland Dysfunction; Keratins
PubMed: 38888283
DOI: 10.1167/iovs.65.6.28 -
Skin Research and Technology : Official... Jun 2024The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined...
BACKGROUND
The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV).
MATERIALS AND METHODS
The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up.
RESULTS
The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements.
CONCLUSION
The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.
Topics: Humans; Vitiligo; Female; Male; Adult; Ultraviolet Therapy; Retrospective Studies; Paeonia; Glucosides; Combined Modality Therapy; Middle Aged; Young Adult; Adrenal Cortex Hormones; Treatment Outcome; Administration, Oral; Plant Extracts; Adolescent; Skin Pigmentation
PubMed: 38887837
DOI: 10.1111/srt.13769