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Cureus May 2024Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) represents a rare group of disorders, that traditionally includes diseases like granulomatosis with...
Propylthiouracil-Induced Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Presenting with Multiple Sterile Abscesses, Mononeuritis Multiplex, and Splenic Vein Thrombosis: A Case Report and Literature Review.
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) represents a rare group of disorders, that traditionally includes diseases like granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). However, AAV can also be triggered by medications such as propylthiouracil (PTU). This article focuses on the subset of drug-induced AAV. We examine how certain medications, notably PTU, can provoke an AAV response, detailing the pathophysiological mechanisms and clinical implications. A 72-year-old female being treated with PTU presented with bilateral hand abscesses, generalized weakness, and frequent falls. Despite initial treatments, her condition worsened, prompting consideration of AAV secondary to PTU. Following appropriate diagnostic procedures and initiation of treatment, including steroids, heparin, and rituximab, the patient showed significant improvement. PTU-induced AAV is a serious, albeit rare, side effect characterized by anti-neutrophil cytoplasmic autoantibodies, with the potential for varied organ involvement and generally a better prognosis than primary AAV. The atypical presentation in this case underscores the importance of clinician vigilance and awareness, ensuring timely diagnosis and appropriate management of this complex condition.
PubMed: 38939251
DOI: 10.7759/cureus.61229 -
Cureus May 2024A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However,...
Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement.
A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However, his clinical picture was complicated by recurrent episodes of neurological symptoms resembling stroke syndrome, which widened the breadth of the diagnostic workup. Extensive investigations, including imaging and biopsies, excluded other possibilities. The patient was treated as probable cerebral vasculitis after identifying new narrowing in the left middle cerebral artery and was treated with pulsed intravenous methylprednisolone, followed by high-dose oral prednisolone and cyclophosphamide. Repeated brain imaging showed further narrowing of the large vessels, which reaffirmed the likelihood of vasculitis necessitating continuation of induction therapy with further maintenance treatment, which led to stabilization of neurological burden and symptom recovery. This case elucidates complexities in reaching the diagnosis of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which can present heterogeneously and mimic other clinical entities such as stroke.
PubMed: 38939237
DOI: 10.7759/cureus.61254 -
Open Veterinary Journal May 2024Diabetes mellitus (DM) is a long-term condition marked by high blood glucose levels caused by insulin resistance which will lead to complications of other diseases such...
BACKGROUND
Diabetes mellitus (DM) is a long-term condition marked by high blood glucose levels caused by insulin resistance which will lead to complications of other diseases such as dyslipidemia, which also affects the health of the liver and kidneys. Butterfly pea flower ( L.) has phenolic and flavonoid compounds which have the potential as herbal medicines for antidiabetics.
AIM
The purpose of this study is to examine the potential of butterfly pea flower extract (BPE) as an antidiabetic, anti-dyslipidemia, and renoprotection.
METHODS
test was performed on Sprague Dawley rats ( L.) induced by Streptozotocin-Nicotinamide and High Fat Diet-Propylthiouracil as models of DM and dyslipidemia, and BPE was administered orally (200, 400, and 800 mg/kg BW) for 28 days. glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), tumor necrosis factor-α (TNF-α), nuclear factor-kappa beta (NF-kB), alkaline phosphatase (ALP), liver albumin levels, serum blood urea nitrogen (BUN), serum creatinine, and serum uric acid (UA), were measured by ELISA and colorimetry methods.
RESULTS
Treatment of BPE 800 mg/kg BW increased levels of GSH-Px, GST, albumin, and serum protein. BPE decreased TNF-α, NF-kB, and ALP. BPE also decreased BUN, serum CR, and serum UA.
CONCLUSION
BPE has the potential to be used as a drug alternative for the treatment of DM and dyslipidemia as well as a hepatoprotective and renoprotective agent.
Topics: Animals; Plant Extracts; Rats, Sprague-Dawley; Rats; Dyslipidemias; Male; Hypoglycemic Agents; Hypolipidemic Agents; Diabetes Mellitus, Experimental; Flowers
PubMed: 38938424
DOI: 10.5455/OVJ.2024.v14.i5.7 -
Cureus May 2024Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of... (Review)
Review
Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of autoantibodies against the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomic production of thyroxine and triiodothyronine. Deciding on a therapeutic approach to this condition presents intricate dilemmas for both clinicians and patients. Each of the three available treatment modalities is grounded in evidence-based medicine, affirming its efficacy. This systematic review and meta-analysis aimed to assess the effect of carbimazole (CBM), radioactive iodine (RAI), and surgery in treating GD and provide evidence-based recommendations for healthcare providers regarding the optimal management of the condition based on a comprehensive analysis of effectiveness, safety, patient satisfaction, and recovery outcomes. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and September 2023. The meta-analysis was carried out using Resource Manager (Revman) 5.4.1. The study found that propylthiouracil (PTU) or methimazole/carbimazole (MMI/CBM) treatment increases the risk of hyperlipidemia in patients with hyperthyroidism. Once in a euthyroid state, glucose tolerance increases; for children with GD, a computer model for customized dosing has been created. To sum up, CBM, surgery, and RAI are all useful treatment options for GD. Using steroids in conjunction with radiation therapy may help prevent Graves' ophthalmopathy (GO).
PubMed: 38910658
DOI: 10.7759/cureus.60829 -
FASEB Journal : Official Publication of... Jun 2024Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase...
Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.
Topics: Animals; Neurogranin; Hypothyroidism; Female; Pregnancy; Mice; Cognitive Dysfunction; Histone Deacetylase 2; Prenatal Exposure Delayed Effects; Histone Deacetylase 1; Down-Regulation; Hippocampus; Male; Histone Deacetylases; Mice, Inbred C57BL; Neuronal Plasticity
PubMed: 38865202
DOI: 10.1096/fj.202400389R -
Frontiers in Pharmacology 2024The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through...
The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using "Scrophulariae Radix-Fritillaria." The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of "Scrophulariae Radix-Fritillaria" were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. "Scrophulariae Radix-Fritillaria" mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by "Scrophulariae Radix-Fritillaria." Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of "Scrophulariae Radix-Fritillaria" were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of "Scrophulariae Radix-Fritillaria" involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.
PubMed: 38828449
DOI: 10.3389/fphar.2024.1206718 -
Aquatic Toxicology (Amsterdam,... Jul 2024Thyroid hormones (THs) act early in ontogenesis, even prior to the differentiation of thyrocytes. Maternal transfer of THs is therefore known to play an essential role...
The generation gap in endocrine disruption: Can the integrated fish endocrine disruptor test (iFEDT) bridge the gap by assessing intergenerational effects of thyroid hormone system disruption?
Thyroid hormones (THs) act early in ontogenesis, even prior to the differentiation of thyrocytes. Maternal transfer of THs is therefore known to play an essential role in early development. Current OECD test guidelines for the assessment of TH system disruption (THSD) do not address inter- or transgenerational effects. The integrated fish endocrine disruptor test (iFEDT), a test combining parental and developmental exposure of filial fish, may fill this gap. We tested the ability of the iFEDT to detect intergenerational effects in zebrafish (Danio rerio): Parental fish were exposed to propylthiouracil (PTU), an inhibitor of TH synthesis, or not exposed. The offspring was submitted to a crossed experimental design to obtain four exposure scenarios: (1) no exposure at all, (2) parental exposure only, (3) embryonic exposure only, and (4) combined parental and embryonic exposure. Swim bladder inflation, visual motor response (VMR) and gene expression of the progeny were analysed. Parental, but not embryonic PTU exposure reduced the size of the swim bladder of 5 d old embryos, indicating the existence of intergenerational effects. The VMR test produced opposite responses in 4.5 d old embryos exposed to PTU vs. embryos derived from exposed parents. Embryonic exposure, but not parental exposure increased gene expression of thyroperoxidase, the target of PTU, most likely due to a compensatory mechanism. The gene expression of pde-6h (phosphodiesterase) was reduced by embryonic, but not parental exposure, suggesting downregulation of phototransduction pathways. Hence, adverse effects on swim bladder inflation appear more sensitive to parental than embryonic exposure and the iFEDT represents an improvement in the testing strategy for THSD.
Topics: Animals; Endocrine Disruptors; Zebrafish; Thyroid Hormones; Water Pollutants, Chemical; Propylthiouracil; Female; Embryo, Nonmammalian; Male; Toxicity Tests
PubMed: 38824743
DOI: 10.1016/j.aquatox.2024.106969 -
Experimental and Clinical... May 2024The objective of this study is to review the association of TAS2R38 polymorphisms and taste phenotypes to bitter compounds (phenylthiocarbamide [PTC]/propylthiouracil...
The objective of this study is to review the association of TAS2R38 polymorphisms and taste phenotypes to bitter compounds (phenylthiocarbamide [PTC]/propylthiouracil [PROP]), and its association among persons who drink alcohol and individuals with smoking behavior. A literature search was carried out in PubMed, ScienceDirect, Cochrane, and Wiley online library databases using the keyword "(Bitter taste receptor genes OR TAS2R38) AND (PROP OR propylthiouracil) AND (PTC OR phenylthiocarbamide)," "(Bitter taste receptor genes OR TAS2R38) AND (alcohol)," "(Bitter taste receptor genes OR TAS2R38) AND (tobacco OR smoker)" to find articles evaluating the association of taste phenotypes and TAS2R38 polymorphisms, and its association among persons who drink alcohol and individuals with smoking behavior. The analysis show that TAS2R38 taster genotype (proline-alanine-valine [PAV] allele) was significantly (OR, 5.88; CI [3.87, 8.95], < .001) associated with taster phenotype for bitter compounds (PTC/PROP), and TAS2R38 nontaster genotype (alanine-valine-isoleucine allele) was significantly (OR, 6.73; CI [4.57, 9.90], < .001) associated with nontaster phenotype for bitter compounds. Further, TAS2R38 taster genotypes (PAV homozygotes and heterozygotes) were significantly associated with higher alcohol intake (OR, 5.15; 95% CI [2.66, 9.98]; < .001) and among individuals with smoking behavior (OR, 1.73; 95% CI [1.24, 2.42]; = .001). This suggests that TAS2R38 single nucleotide polymorphisms can be identified by clinically assessing taste phenotype status for bitter compounds and can be used as a potential therapeutic target in the prevention and treatment of harmful higher alcohol intake and smoking behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38815112
DOI: 10.1037/pha0000728 -
Environmental Toxicology and Chemistry May 2024There is increasing concern regarding pollutants disrupting the vertebrate thyroid hormone (TH) system, which is crucial for development. Thus, identification of TH...
There is increasing concern regarding pollutants disrupting the vertebrate thyroid hormone (TH) system, which is crucial for development. Thus, identification of TH system-disrupting chemicals (THSDCs) is an important requirement in the Organisation for Economic Co-operation and Development (OECD) testing framework. The current OECD approach uses different model organisms for different endocrine modalities, leading to a high number of animal tests. Alternative models compatible with the 3Rs (replacement, reduction, refinement) principle are required. Zebrafish embryos, not protected by current European Union animal welfare legislation, represent a promising model. Studies show that zebrafish swim bladder inflation and eye development are affected by THSDCs, and the respective adverse outcome pathways (AOPs) have been established. The present study compared effects of four THSDCs with distinct molecular modes of action: Propylthiouracil (PTU), potassium perchlorate, iopanoic acid, and the TH triiodothyronine (T3) were tested with a protocol based on the OECD fish embryo toxicity test (FET). Effects were analyzed according to the AOP concept from molecular over morphological to behavioral levels: Analysis of thyroid- and eye-related gene expression revealed significant effects after PTU and T3 exposure. All substances caused changes in thyroid follicle morphology of a transgenic zebrafish line expressing fluorescence in thyrocytes. Impaired eye development and swimming activity were observed in all treatments, supporting the hypothesis that THSDCs cause adverse population-relevant changes. Findings thus confirm that the FET can be amended by TH system-related endpoints into an integrated protocol comprising molecular, morphological, and behavioral endpoints for environmental risk assessment of potential endocrine disruptors, which is compatible with the 3Rs principle. Environ Toxicol Chem 2024;00:1-18. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
PubMed: 38804632
DOI: 10.1002/etc.5878 -
Nutrients Apr 2024Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the gene. Three SNPs form two common (AVI, PAV) and four rare...
Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three SNPs that result in three diplotypes-SLN/SLN, FVS/SLN, and FVS/FVS-which make up 25.1%, 44.9%, and 23.9% of our sample. These haplotypes show minimal linkage disequilibrium with so we examined the suprathreshold bitterness as a function of both. The participants ( = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the haplotypes explained ~29% ( < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the diplotypes (independent of the haplotypes) explained ~7-8% of the variation in the bitterness ratings ( = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the diplotype and food intake.
Topics: Humans; Propylthiouracil; Receptors, G-Protein-Coupled; Polymorphism, Single Nucleotide; Female; Taste; Male; Adult; Haplotypes; Homozygote; Young Adult; Taste Threshold
PubMed: 38732607
DOI: 10.3390/nu16091357