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Auris, Nasus, Larynx Jun 2024Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone,...
OBJECTIVE
Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons.
METHODS
To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test.
RESULTS
Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days.
CONCLUSION
These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.
Topics: Animals; Olfactory Bulb; Methimazole; Mice; Cell Movement; Antithyroid Agents; Olfactory Nerve; Olfactory Marker Protein; Disease Models, Animal; Male
PubMed: 38522356
DOI: 10.1016/j.anl.2024.01.009 -
The Journal of Endocrinology May 2024Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary...
Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1β, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.
Topics: Rats; Female; Male; Humans; Animals; Antioxidants; Hydrogen Peroxide; Goiter; Oxidative Stress; Thyrotropin; Inflammation
PubMed: 38513357
DOI: 10.1530/JOE-24-0009 -
Medicine Mar 2024A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk... (Review)
Review
RATIONALE
A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic.
PATIENT CONCERN
A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month.
DIAGNOSIS
Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy.
INTERVENTION
Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy.
OUTCOME
After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later.
CONCLUSION
COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.
Topics: Female; Humans; Middle Aged; Iodine Radioisotopes; Pandemics; COVID-19; Graves Disease; Hyperthyroidism; Methimazole; Antithyroid Agents; Liver
PubMed: 38489722
DOI: 10.1097/MD.0000000000037456 -
SAGE Open Medical Case Reports 2024Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth...
Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth restriction, small for gestational age, and neonatal Graves disease. Intrauterine growth restriction and small for gestational age are associated with hypoglycemia and transient neonatal hyperinsulinism. Neonatal Graves disease with severe persistent hypoglycemia has not been well described. We present the case of a female patient born at 34 weeks and 3 days with a birth weight of 1.6 kg (fifth percentile) to a mother with recent treatment for Graves disease. Prenatal ultrasounds were significant for intrauterine growth restriction and small for gestational age. The mother did not begin hyperthyroidism medical therapy until 23 weeks and 2 days of gestation. After the infant was born, the infant not only had symptoms of hyperthyroidism such as tachycardia and abnormal thyroid values but also had persistent hypoglycemia, which could be due to maternal propranolol usage, prematurity, IUGR, increased metabolism due to neonatal Graves, and transient stress-induced hyperinsulinism. The infant was started on methimazole for hyperthyroidism and propranolol for tachycardia. She was also started on diazoxide for persistent hypoglycemia. By 6 months of age, the hyperthyroidism and hypoglycemia had resolved. This is an interesting case of neonatal Graves disease with severe persistent hypoglycemia which we suspect is due to transient neonatal hyperinsulinism induced by multiple stress responses.
PubMed: 38463451
DOI: 10.1177/2050313X241237433 -
JCEM Case Reports Mar 2024Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL...
Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free thyroxine (FT4) with a suppressed thyrotropin. Hemodialysis was initiated. Further testing revealed a negative antithyroid antibody panel, an enlarged fatty thyroid per thyroid ultrasound and neck computed tomography, and normal 24-hour uptake on radioactive iodine uptake scan. Both renal and thyroid core biopsies showed amyloid deposits, with the latter confirming benign adipose tissue with entrapped thyroid follicles. Given her rising FT4 levels and persistent tachycardia, methimazole and atenolol were initiated. FT4 levels nearly normalized after uptitration of methimazole and dosing after dialysis. Although the etiopathogenesis and natural history of DTL remain unclear, we discuss the possible mechanisms of thyrotoxicosis in our patient.
PubMed: 38440128
DOI: 10.1210/jcemcr/luae030 -
ChemPlusChem Jun 2024Investigating the reactivity of small nucleophilic scaffolds is a strategic approach for the design of new catalysts aiming at effective detoxification processes of...
Investigating the reactivity of small nucleophilic scaffolds is a strategic approach for the design of new catalysts aiming at effective detoxification processes of organophosphorus compounds. The drug methimazole (MMZ) is an interesting candidate featuring two non-equivalent nucleophilic centers. Herein, phosphoryl transfer reactions mediated by MMZ were assessed by means of spectrophotometric kinetic studies, mass spectrometry (MS) analyses, and density functional theory (DFT) calculations using the multi-electrophilic compound O,O-diethyl 2,4-dinitrophenyl phosphate (DEDNPP). MMZ anion acts primarily as an S-nucleophile, exhibiting a nucleophilic activity comparable to that of certain oximes featuring alpha-effect. Selective nucleophilic aromatic substitution was observed, consistent with the DFT prediction of a low energy barrier. Overall, the results bring important advances regarding the mechanistic understanding of nucleophilic dephosphorylation reactions, which comprises a strategic tool for neutralizing toxic organophosphates, hence promoting chemical security.
PubMed: 38412020
DOI: 10.1002/cplu.202300756 -
Therapie Feb 2024The safety profile of methimazole (MMI) seems to be better than propylthiouracil in the management of hyperthyroidism. It is therefore advisable to use IMM as the first...
PURPOSE
The safety profile of methimazole (MMI) seems to be better than propylthiouracil in the management of hyperthyroidism. It is therefore advisable to use IMM as the first choice in Graves' patients. It is important to keep this drug in patients regardless of minor side effects. We report a case series of MMI-induced urticaria and provide a stepwise protocol for the safe re-administration of MMI.
METHODS
It was a retrospective case series including all patients having manifested urticaria following MMI intake for hyperthyroidism; notified to the Pharmacovigilance Unit of the Clinical Pharmacology Department (March 2013-January 2022).
RESULTS
We have included 11 patients (SR: 0.22). The median time interval between the start of MMI and the onset of urticaria averaged 14.5 days. The median daily dose of MMI was 40mg. MMI was interrupted in all patients. Urticaria has progressively resolved after drug interruption and antihistamine intake. Reintroduction of MMI was performed in 10/11 patients as follows: one quarter of the daily dose on the first day, half of the daily dose on the 4th day, the three quarters of the daily dose on the 7th day, to reach the scheduled total dose on the 10th day. Cetirizine was added at the time of reintroduction and withdrawn 2 weeks later. All the patients were successfully controlled.
CONCLUSION
Given the importance of this drug in the management of hyperthyroidism, MMI should not be withdrawn in cases of urticaria. After the resolution of urticaria, a gradual reintroduction of MMI should be attempted with concomitant antihistamine therapy.
PubMed: 38403562
DOI: 10.1016/j.therap.2023.12.006 -
Medicine Feb 2024Methimazole (MMI) is the first-line agent in the treatment of hyperthyroidism. However, rare but severe cholestatic jaundice may occur. Therapeutic plasma exchange (TPE)...
RATIONALE
Methimazole (MMI) is the first-line agent in the treatment of hyperthyroidism. However, rare but severe cholestatic jaundice may occur. Therapeutic plasma exchange (TPE) may provide an alternative treatment for such patients and they received thyroidectomy/radioactive iodine ablation or continued oral anti hyperthyroidism medication immediately after TPE session in the reported literatures. The case reported here is, to our knowledge, the first to describe the long interval between anti hyperthyroidism therapy and TPE in such patients.
PATIENT CONCERNS
A 49-year-old Chinese woman had developed worsening jaundice 3 weeks after receiving methimazole (20 mg/day) for the treatment of hyperthyroidism secondary to Graves' disease (GD). Additionally, she had a 2-year history of type 2 diabetes.
DIAGNOSIS
Hyperthyroidism secondary to GD, MMI-induced severe cholestatic jaundice and type 2 diabetes.
INTERVENTIONS
Methimazole was discontinued and the patient received 3 times of TPE, about 3-month glucocorticoid treatment, insulin administration accordingly and other conventional liver-protecting therapy.
OUTCOMES
Her thyroid function was stabilized with small dose of thyroxine substitution and euthyroid status persisted after thyroxine discontinuation until hyperthyroidism recurred 7 months later while her cholestatic jaundice was eventually recovered by about 3-month glucocorticoid therapy.
LESSONS
Due to the complex interplay between liver function and thyroid hormones, there may be unusual changes of thyroid function in GD patients with severe liver injury after TPE. By this case, we want to highlight the importance of a closely following up of thyroid function in order to deliver appropriate health suggestions for patients.
Topics: Humans; Female; Middle Aged; Methimazole; Thyroxine; Plasma Exchange; Jaundice, Obstructive; Diabetes Mellitus, Type 2; Iodine Radioisotopes; Glucocorticoids; Thyroid Neoplasms; Neoplasm Recurrence, Local; Graves Disease; Hyperthyroidism; Antithyroid Agents
PubMed: 38394504
DOI: 10.1097/MD.0000000000037074 -
Physiology & Behavior Apr 2024An increasing body of evidence suggests that the state of hyperalgesia could be socially transferred from one individual to another through a brief empathetic social...
An increasing body of evidence suggests that the state of hyperalgesia could be socially transferred from one individual to another through a brief empathetic social contact. However, how the social transfer of pain develops during social contact is not well-known. Utilizing a well-established mouse model, the present study aims to study the functional role of visual and olfactory cues in the development of socially-transferred mechanical hypersensitivity. Behavioral tests demonstrated that one hour of brief social contact with a conspecific mouse injected with complete Freund's adjuvant (CFA) was both sufficient and necessary for developing socially-transferred mechanical hypersensitivity. One hour of social contact with visual deprivation could not prevent the development of socially-transferred mechanical hypersensitivity, and screen observation of a CFA cagemate was not sufficient to develop socially-transferred mechanical hypersensitivity in bystanders. Methimazole-induced olfactory deprivation, a compound with reversible toxicity on the nasal olfactory epithelium, was sufficient to prevent the development of socially-transferred mechanical hypersensitivity. Intriguingly, repeated but not acute olfactory exposure to the CFA mouse bedding induced a robust decrease in 50 % paw withdrawal thresholds (50 %PWTs) to mechanical stimuli, an effect returned to the baseline level after two days of washout with clean bedding. The findings strongly indicate that the normal olfactory function is crucial for the induction of mechanical hypersensitivity through brief empathetic contact, offering valuable insights for animal housing in future pain research.
Topics: Mice; Male; Animals; Mice, Inbred C57BL; Hyperalgesia; Disease Models, Animal; Pain; Inflammation
PubMed: 38378074
DOI: 10.1016/j.physbeh.2024.114499 -
Indian Journal of Endocrinology and... 2023Thyrotoxicosis is not uncommon after immunization. It is known as 'autoimmune/autoinflammatory syndrome by adjuvants (ASIA syndrome)' and is caused by immunological...
INTRODUCTION
Thyrotoxicosis is not uncommon after immunization. It is known as 'autoimmune/autoinflammatory syndrome by adjuvants (ASIA syndrome)' and is caused by immunological reaction to adjuvants. However, there is insufficient information on thyrotoxicosis after COVID-19 vaccination in the Indian subcontinent.
AIMS/OBJECTIVES
To investigate the spectrum of thyrotoxicosis after COVID-19 immunization.
SETTINGS AND DESIGN
A single-centre retrospective study was conducted at a tertiary care academic institute in India.
MATERIALS AND METHODS
We studied the clinical symptoms, biochemical markers, imaging characteristics and treatment of every patient who was diagnosed with thyrotoxicosis within 60 days of receiving the COVID-19 vaccine.
RESULTS
Following COVID-19 vaccination, we diagnosed ten people (mean age 39.9 years, range 22-63 years) with thyrotoxicosis [Graves' disease (GD, -6) and subacute thyroiditis (SAT, -4)]. The typical duration for symptoms to appear was 2 to 60 days. The majority of patients (-9) received the COVISHIELD™ vaccine, whereas only one received the COVAXIN vaccine. After vaccination, two patients with GD developed mildly severe Graves' orbitopathy, with symptoms emerging two days and sixty days later, respectively. Anti-thyroid drugs (methimazole or carbimazole) were required for all GD patients. All SAT patients were treated conservatively with nonsteroidal anti-inflammatory medications and had positive outcomes.
CONCLUSIONS
SAT, GD and GO may occur as a manifestation of ASIA syndrome, following immunization with COVISHIELD™ and COVAXIN. Despite the obvious benefits of the COVID-19 vaccine, clinicians should be aware of any potential autoimmune and inflammatory thyroid problems.
PubMed: 38371178
DOI: 10.4103/ijem.ijem_202_23