Administration Of Methimazole Research Articles

Histological changes in the olfactory bulb and rostral migratory stream due to interruption of olfactory input

ObjectivePeriglomerular 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. MethodsTo 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. ResultsOlfactory 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. ConclusionThese 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.

Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model.

In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism. A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment. Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight. A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 d after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e., proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

Minimal change disease associated with Graves’ disease and methimazole use

Introduction. Graves' disease causes kidney injury through multiple mechanisms, including the treatment for this condition. Nephrotic syndrome due to minimal change disease (MCD) is an unusual form of such kidney injury; the association between methimazole use and MCD is also rare.&#x0D; Case presentation. 36-year-old woman with a history of Graves' disease in use of methimazole for several months, who presented with edematous syndrome due to nephrotic syndrome associated with a KDIGO stage 3 acute kidney injury. Thionamide-induced hypothyroidism and the need of thyroid hormone replacement therapy was evidenced at the time of consultation. Based on a renal biopsy, the patient was diagnosed with MCD. Her condition worsened as she experienced oliguria and hypervolemia, and renal replacement therapy with hemodialysis was temporarily required. Methimazole administration was suspended, and treatment consisting of prednisolone administration and levothyroxine supplementation was started, achieving hemodialysis suspension, gradual improvement of proteinuria until remission and full and maintained recovery of renal clearance. Radioiodine therapy was implemented as definitive treatment for Graves' disease, obtaining a successful outcome.&#x0D; Conclusions. Graves' disease and methimazole use are possible causes of minimal change disease. Systemic corticosteroid therapy is a possible management. However, further basic, clinical and epidemiological research on this subject is required.

Amiodarone-Induced Multi-Systemic Toxicity Involving the Liver, Lungs, Thyroid, and Eyes: A Case Report

ObjectivesAmiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes.Case PresentationA 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 μIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months.ConclusionsThis case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis.

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

Morphological changes in liver of methimazole treated rats, a pilot study

BACKGROUND &amp; OBJECTIVE: Thyrotoxicosis is a disease in which thyroid hormones are raised, and we have seen multiple patients suffering from this ailment in Pakistan. Methimazole is an anti-thyroid drug for thyrotoxicosis. Hepatotoxicity and liver ailments were common with methimazole prescribed for hypothyroid patients. Hypothyroidism, a common side effect of this drug, has been seen in a majority of patients, but liver toxicity remained unaddressed. So, in this study, we have observed histological changes in the liver after methimazole administration.&#x0D; METHODOLOGY: The pilot study was carried out in the University of Health Sciences (UHS), Lahore, and was ended in twenty-one days. We divided animals in 2 groups. Each group comprises 12 animals. Group-I was negative control, and water was given through the oral route for 21 days. Group-II was administered methimazole orally 60mg/kg/day for twenty-one days. At the end;S animals were dissected, and livers were removed for histological examination.&#x0D; RESULTS: The histological picture of the liver showed 75% severe disruption in liver architecture, inflammation, and fatty change in group 2, indicating liver damage.&#x0D; CONCLUSION: Methimazole, hepatotoxic with discernable damage to its architecture, epithelium, and inflammatory changes.

A Rare Case of Necrotizing Fasciitis as Side Effect of Methimazole Administration for Basedow Disease

A rare case of agranulocytosis due to Methimazole administration for Basedow disease is presented. After 30 days since the therapy beginning a 45 year old female patient has developed a necrotizing fasciitis on both legs, with muscle bellies and Achille’s tendon exposure. Immediate surgical debridement was necessary to save her life and control the progression of infection. Several plastic surgery procedures were performed to accomplish wounds healing (vacuum-assisted closure therapy, dermal substitute, free flap, skin graft), and after 75 days the patient was discharged. An intensive rehabilitation program permitted a complete functional recovery. After 12 months a reshaping procedure was performed to improve right leg and ankle contour. The close cooperation between endocrinologist and surgeon revealed to be essential to perform a safe surgery and to permit the return to the job and daily activities.

Early postnatal hypothyroidism reduces juvenile play behavior, but prenatal hypothyroidism compensates for these effects

Perinatal hypothyroidism causes long-lasting effects on behavior, including hyperactivity, cognitive delays/deficits, and a reduction in anxiety. Although there is some evidence that hypothyroidism during fetal development in humans has been associated with later autism spectrum disorder diagnosis or autism-like traits, the relationships between early thyroid hormones and social behaviors are largely unknown. Previously, we found that a moderate dose of the hypothyroid-inducing drug methimazole during embryonic and postnatal development dramatically increased juvenile play in male and female rats. The goal of the current study was to determine the extent to which thyroid hormones act in prenatal or postnatal development to organize later social behaviors. Subjects were exposed to methimazole in the drinking water during prenatal (embryonic day 12 to birth), postnatal (birth to postnatal day 23), or pre- and postnatal development; control animals received regular drinking water throughout the experiment. They were tested for play behavior as juveniles (P30–32). We found an interaction between pre- and postnatal methimazole administration such that postnatal hypothyroidism decreased some play behaviors, whereas sustained pre- and postnatal hypothyroidism restored play to control levels. The effects were similar in males and females. To our knowledge, this is the first report of an interaction between pre- and postnatal hypothyroidism on later behavior. The complexity of the timing of these effects may help explain why epidemiological studies have not consistently found a relationship between gestational hypothyroidism and later behavior.

Reduction of TMAO level enhances the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red, Perl’s staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells with no obvious effect on the M1 polarization. In conclusion, the present study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.

Transdermal Absorption of Methimazole- a Cat’s Tale

Introduction: In modern civilization different kinds of animals live with us as pets. These pets have different diseases and are on medications. Close contact with animals can cause medication adverse reactions or may worsen pre-existing conditions in humans. Here we present an interesting case of hypothyroidism worsened by transdermal absorption of methimazole administered for feline hyperthyroidism. Case History: 66-year-old Caucasian female with past medical history of postoperative hypothyroidism s/p total thyroidectomy secondary to multinodular goiter due to Hashimoto’s thyroiditis with a 0.2 cm papillofollicular microcarcinoma and 0.7 cm follicular adenoma presented for follow up. She complained of weight gain, lethargy and dry skin for the past 4 months. She was on a stable dose of levothyroxine 112 mcg daily for the past year. She took her pill correctly and did not miss any doses. Her other medical problems were impaired fasting glucose, osteopenia and B12 deficiency. Her repeat thyroid function tests showed TSH 11.2 mc IU/ l (0.4 -4) (TSH - 0.538 mc IU/ L 6 months back), T4 - 6.8 mcg/ dl (4.5 - 12) (T4 8.9 6 months back). She had a measurable serum thyroglobulin of 0.4 ng/ml with antithyroglobulin antibody 11 IU/ml (<115) consistent with some residual thyroid tissue despite her history of a “total thyroidectomy”. Due to recent worsening of her symptoms with elevated TSH on background of previous stable levothyroxine requirement, further detailed history was taken. She reported that her cat was suffering from hyperthyroidism, treated with methimazole 10 mg daily. The patient used to cut the pill in half with bare hands and fed it to her pet. She also used to handle wet methimazole that her cat coughed up. Her levothyroxine dose was continued at 112 mcg daily. The patient was advised to use gloves before feeding and wash her hands after feeding her cat. Her symptoms resolved after she took precautions and TSH normalized to 1.170 mc IU/ l with T4 7.6 two months later. Conclusion: Absorption of methimazole by transdermal administration has been shown in cats1. A study by Kasraee et al showed safety of a 5% topical methimazole application for treatment of post inflammatory hyperpigmentation in humans with no change in thyroid function tests2. Our case contradicts this study and indicates that methimazole might be absorbed transdermally in humans. To conclude, more studies are needed to study the effect of transdermal administration of methimazole in humans.

Associations between gut microbiota and thyroidal function status in Chinese patients with Graves' disease.

The imbalance of gut microbiota has been linked to manifold endocrine diseases, but the association with Graves' disease (GD) is still unclear. The purpose of this study was to investigate the correlation between human gut microbiota and clinical characteristics and thyroidal functional status of GD. 14 healthy volunteers (CG) and 15 patients with primary GD (HG) were recruited as subjects. 16SrDNA high-throughput sequencing was performed on IlluminaMiSeq platform to analyze the characteristics of gut microbiota in patients with GD. Among them, the thyroid function of 13 patients basically recovered after treatment with anti-thyroid drugs (oral administration of Methimazole for 3-5months). The fecal samples of patients after treatment (TG) were sequenced again, to further explore and investigate the potential relationship between dysbacteriosis and GD. In terms of alpha diversity index, the observed OTUs, Simpson and Shannon indices of gut microbiota in patients with GD were significantly lower than those in healthy volunteers (P < 0.05).The difference of bacteria species was mainly reflected in the genus level, in which the relative abundance of Lactobacillus, Veillonella and Streptococcus increased significantly in GD. After the improvement of thyroid function, a significant reduction at the genus level were Blautia, Corynebacter, Ruminococcus and Streptococcus, while Phascolarctobacterium increased significantly (P < 0.05). According to Spearman correlation analysis, the correlation between the level of thyrotropin receptor antibody (TRAb) and the relative abundance of Lactobacillus and Ruminococcus was positive, while Synergistetes and Phascolarctobacterium showed a negative correlation with TRAb. Besides, there were highly significant negative correlation between Synergistetes and clinical variables of TRAb, TPOAb and TGAb (P < 0.05, R < - 0.6). This study revealed that functional status and TRAb level in GD were associated with composition and biological function in the gut microbiota, with Synergistetes and Phascolarctobacterium protecting the thyroid probably, while Ruminococcus and Lactobacillus may be novel biomarkers of GD.

Single or Repeated Ablation of Mouse Olfactory Epithelium by Methimazole

Odor-detecting olfactory sensory neurons residing in the nasal olfactory epithelium (OE) are the only neurons in direct contact with the external environment. As a result, these neurons are subjected to chemical, physical, and infectious insults, which may be the underlying reason why neurogenesis occurs in the OE of adult mammals. This feature makes the OE a useful model for studying neurogenesis and neuronal differentiation, with the possibility for systemic as well as local administration of various compounds and infectious agents that may interfere with these cellular processes. Several different chemical compounds have been shown to cause toxic injury to the OE, which can be used for OE ablation. We, and others, have found that the systemic administration of the hyperthyroid drug, methimazole, reliably causes olfactotoxicity as a side effect. Here, we outline an OE lesioning protocol for single or repeated ablation by methimazole. A single methimazole administration can be used to study neuroepithelial regeneration and stem cell activation, while repeated ablation and regeneration of OE enable the study of tissue stem cell exhaustion and generation of tissue metaplasia.

The Impact of Ovariectomy on Olfactory Neuron Regeneration in Mice.

Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous system, and have the ability to regenerate even after an individual has reached maturity. Olfactory receptor cells also regenerate after experimentally induced degeneration. The purpose of this study is to observe the influence of estrogen depletion induced by ovariectomy on olfactory nerve regeneration. Female mice underwent bilateral ovariectomy at 8 weeks of age and received intraperitoneal administration of methimazole 1 week later. At 2, 4, and 6 weeks after methimazole administration, the olfactory mucosa was analyzed histochemically to determine olfactory epithelium (OE) thickness, olfactory marker protein distribution, and Ki-67 immunoreactivity. Furthermore, 2 weeks after ovariectomy, trkA protein distribution in the OE and nerve growth factor (NGF) levels in the olfactory bulb were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Our results showed that in ovariectomized mice OMP, Ki-67, and trkA-immunopositive cells expression decreased at 2 weeks after methimazole injection, a time point at which regeneration is underway. At this same time point, although NGF production in the olfactory bulb had increased before methimazole administration, no differences were observed between the ovx and control groups. These results suggest that estrogen depletion induces a suppressive effect on regeneration of olfactory neurons, and that estrogen may have a potential use in the treatment of sensorineural olfactory dysfunction.

Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment.

PurposeWe evaluated the severity of olfactory disturbance (OD) in the murine model of allergic rhinitis (AR) and local allergic rhinitis (LAR) in mice. We also investigated the therapeutic effect of an intranasal steroid on OD.MethodsForty BALB/c mice were divided into 5 groups (n = 8 for each). The control group was sensitized intraperitoneally (i.p.) and challenged intranasally (i.n.) with saline. Mice in the AR group got i.p. and i.n. ovalbumin (OVA) administration for AR induction. The LAR group was challenged i.n. with 1% OVA for inducing local nasal allergic inflammation, without inducing the systemic allergy. The OD group got an i.p. methimazole administration (75 mg/kg) to induce total destruction of olfactory mucosa. Mice in the intranasal budesonide group received i.n. budesonide (12.8 μg per time, 30 minutes after the i.n. OVA challenge) while using OVA to cause systemic allergies. We conducted a buried-food pellet test to functionally assess the degree of OD in each group by measuring the time taken until finding hidden food. We evaluated the damage to olfactory epithelium using histopathologic evaluation and compared the degree of olfactory marker protein (OMP) expression in olfactory epithelium using immunofluorescent staining.ResultsMice of the AR (81.3 ± 19.8 seconds) and LAR groups (66.2 ± 12.7 seconds) spent significantly more time to detect the pellets than the control group (35.6 ± 12.2 seconds, P < 0.01). After treatment, the intranasal budesonide group exhibited significantly better results (35.8 ± 11.9 seconds) compared with the AR and LAR groups (P < 0.01). The AR and LAR groups showed considerable olfactory epithelial damage and suppression of OMP expression compared with the control group. In the intranasal budesonide group, the olfactory lesions and OMP expression had improved substantially.ConclusionsOD may be caused by olfactory epithelial damage and suppression of OMP expression in nasal allergic inflammation and could be reversed using an intranasal steroid.

Integrated microRNA and proteome analysis reveal a regulatory module in hepatic lipid metabolism disorders in mice with subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) is becoming a global health problem due to its increasing prevalence and potential adverse effects, including cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD). However, the association between SCH and NAFLD remains controversial. MicroRNAs (miRNAs/miRs) have been reported to be implicated in lipid metabolism disorders; however, how miRNAs regulate hepatic lipid metabolism in SCH mice remains unknown. The present study investigated miRNA alterations and proteome profiles in an SCH mouse model, which was generated by methimazole administration in mice for 16 weeks. Next, the profiles of 17 miRNAs that are critical to hepatic lipid metabolism and the proteome were investigated using reverse transcription-quantitative polymerase chain reaction and iTRAQ labeling in the liver specimens of SCH (n=9) and control (n=7) mice. Putative target prediction of miRNAs was also conducted using TargetScan and miRanda. Compared with the control mice, SCH mice had 8 miRNAs and 36 proteins with significantly different expression in the liver tissues. Furthermore, a regulatory module containing 3 miRNAs (miR-34a-5p, miR-24-3p and miR-130a-3p) and 4 proteins (thioredoxin, selenium-binding protein 2, elongation factor 1β and prosaposin) was identified. Overall, integrated analysis of miRNAs and the proteome highlighted a regulatory module between miRNAs and proteins, which, to a certain extent, may contribute to a better understanding of hepatic lipid metabolism disorders in SCH mice.

Effects of Commiphora mukul, Withania somnifera and Thyroxine on Thyroid Profile in Murine Model of Hypothyroidism

Introduction: Thyroid disorders, especially hypothyroidism are on the rise these days due to unhealthy lifestyle and nutritional deficiencies which calls for research in this domain. Monotherapy with thyroxine is considered the main line of treatment up till now but besides its beneficial role in normalizing thyroid hormone levels, it has serious cardiac effects which leads to the search of safer natural remedies. Commiphora mukul and Withanias omnifera are considered two such plants with beneficial role in correcting T3 and T4 levels respectively. However keeping in mind the diagnostic importance of TSH, the effects of these phyto extracts on TSH levels needs to be established. Aims &amp; Objectives: So the present study is designed to explore the effects of Ethanolic extract of Commiphora mukul (CMEE) and Withania somnifera (WSEE) on T3, T4 and TSH levels keeping thyroxine as a gold standard in murine model of hypothyroidism. Place and duration of study: This study was carried out in the animal house of PGMI, Lahore. Total duration of study was 38 days. Material &amp; Methods: 50 female rats were divided into 5 groups. G-1 the control group. G-2 received methimazole 60mg/kg/day for 21 days in order to induce hypothyroidism and left untreated for self recovery &amp; G3-5 were induced with methimazole in the same way. After induction all the groups were treated for 15 days, G-3: CMEE 0.2g/kg/day orally, G4: WSEE 1.4g/kg/day orally and G-5 received the gold standard Thyroxin 0.6μg/100gm BW S/C. Thyroid function tests were performed in all groups on Day 1, repeated on Day 22 after methimazole administration and on Day 38 following completion of treatment. Results: The results showed that both CMEE and WSEE corrected T3 and T4 levels to significant extent. CMEE had more effect on T3 levels whereas WSEE corrected T4 levels more. TSH levels were also reverted to normal showing the potential of both these extracts to correct TSH besides T3, T4 levels. Conclusion: This proves that these extracts may play a significant role in correcting thyroid profile (T3, T4 &amp; TSH) if used clinically for the treatment of hypothyroidism. However, clinical research is highly recommended in this domain. Key words: Commiphora mukul, Withania somnifera, hypothyroidism, thyroxine.

Treatment of Graves' hyperthyroidism with thionamides: a position paper on indications and safety in pregnancy.

Graves' disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves' hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI. Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter. This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.

Long-term outcome of cats with acquired myasthenia gravis without evidence of a cranial mediastinal mass.

BackgroundAcquired myasthenia gravis (AMG) is increasingly recognized in cats, yet information regarding the natural history of the disease, treatment, and outcome including occurrence of immune and spontaneous remission remains limited.ObjectiveTo determine the long‐term outcome of cats with AMG without evidence of a cranial mediastinal mass (CMM).AnimalsEight cats diagnosed with AMG without evidence of a CMM.MethodsRetrospective case series. The medical records of cats diagnosed with AMG between 2005 and 2018 from 2 veterinary referral hospitals were reviewed for inclusion. Inclusion criteria consisted of a diagnosis of AMG, thoracic imaging, serum biochemistry including measurement of creatine kinase, and a CBC. Exclusion criteria were the presence of an identifiable CMM, or administration of methimazole or carbimazole.ResultsAll cats had an excellent long‐term outcome, achieving immune remission within 6 months of diagnosis, including 4 cats that did not receive any treatment and whose natural course of disease involved spontaneous remission. Clinical presentation was heterogeneous, and skeletal muscle weakness and fatigability induced or exacerbated by the wheelbarrow exercise stress test were the most consistent abnormalities associated with AMG.Conclusion and Clinical ImportanceCats diagnosed with AMG without evidence a CMM have a favorable outcome and frequently achieve immune remission. Moreover, the natural history of AMG in cats includes spontaneous remission when there is no evidence of a CMM. Attempting to rule out the presence of a CMM therefore refines prognosis, and treatment is not always necessary in this disease population.

Increased Remission Rates After Long-Term Methimazole Therapy in Patients with Graves' Disease: Results of a Randomized Clinical Trial.

Background: Studies differ regarding whether, compared with courses of conventional duration, longer-term antithyroid drug treatment increases frequency of remission in patients with Graves' hyperthyroidism. We prospectively conducted a randomized, parallel-group study comparing relapse rates in patients receiving longer-term versus conventional-length methimazole therapy. We also sought variables associated with relapse following the latter. Methods: We enrolled 302 consecutive patients with untreated first episodes of Graves' hyperthyroidism. After 18-24 months of methimazole, 258 patients (85.4%) were randomized to an additional 36-102-month courses ("long-term group": n = 130; scheduled total time on methimazole: 60-120 months) or discontinuation of methimazole ("conventional group": n = 128). Patients were followed 48 months postmethimazole cessation. We performed Cox proportional hazards modeling to identify factors associated with relapse after conventional courses. Results: Methimazole was given for 95 ± 22 months in long-term patients and 19 ± 3 months in the conventional group. Fourteen patients experienced cutaneous reactions and 2 liver enzyme elevations during the first 18 months of treatment; no further methimazole-related reactions were observed despite therapy for up to another 118 months. Hyperthyroidism recurred within 48 months postmethimazole withdrawal in 15% (18/119) of long-term patients versus 53% (65/123) of conventional group patients. In the conventional group, older age, higher triiodothyronine or thyrotropin receptor antibody concentrations, lower thyrotropin concentration, or possession of the rs1879877 CD28 polymorphism or the DQB1-05 HLA polymorphism were independently associated with relapse. Conclusion: Administration of low-dose methimazole for a total of 60-120 months safely and effectively treats Graves' hyperthyroidism, with much higher remission rates than those attained by using conventional 18-24-month courses.