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Saudi Pharmaceutical Journal : SPJ :... Nov 2023Potassium iodide (KI) is a treatment to neutralize radioactive agents that could be inhaled or ingested in nuclear incidents. The inorganic salt KI constitutes a source...
OBJECTIVES
Potassium iodide (KI) is a treatment to neutralize radioactive agents that could be inhaled or ingested in nuclear incidents. The inorganic salt KI constitutes a source of iodine, which in the body acts by accumulating in the thyroid gland, producing its saturation, and thus preventing the fixation of radioactive iodine species. In Spain, the Military Defence Pharmacy Centre (CEMILFARDEF) was challenged to develop this antidote to be distributed among the population surrounding nuclear power plants, in only one new solid pharmaceutical form for oral administration, in order to replace the two pharmaceutical forms available, which are capsules for adults and oral solution for children, considered less versatile.
METHODS
A selection of excipients was carried out to achieve pharmacotechnical behaviour suitable for the industrial manufacture of potassium iodide in tablets, complying with the pre-established process and finished product quality parameters. The development allowed the preparation of three industrial-sized batches on which the stability of the developed formulation was studied.
RESULTS
An uncoated 65 mg double-scored potassium iodide tablet was developed using easily accessible excipients in the formulation and direct compression as the manufacturing method. The formula complied with the stability tests, with which the development carried out can respond to the eventual demand that its elaboration would entail in the event of nuclear incidents.
CONCLUSIONS
The developed formulation of a 65 mg double-scored potassium iodide tablet allows the great variability of user needs, from infants to adults with a single pharmaceutical form, which additionally implies logistical benefits in distribution, stock control and appropriate renewal according expiration dates, among the population surrounding nuclear power plants and available to deployed military personnel, in the event of potential nuclear incidents.
PubMed: 37868644
DOI: 10.1016/j.jsps.2023.101814 -
The Journal of Clinical Endocrinology... Mar 2024Iodine, combined with antithyroid drugs, is recommended as an initial pharmacologic treatment for thyroid storm according to some clinical guidelines. However, the...
PURPOSE
Iodine, combined with antithyroid drugs, is recommended as an initial pharmacologic treatment for thyroid storm according to some clinical guidelines. However, the clinical efficacy of iodine in managing thyroid storm remains unexplored. This study aimed to determine whether early potassium iodide (KI) use is associated with mortality in patients hospitalized for thyroid storm.
METHODS
Using the Japanese Diagnosis Procedure Combination database, we identified patients hospitalized with thyroid storm between July 2010 and March 2022. We compared in-hospital mortality, length of stay, and total hospitalization costs between patients who received KI within two days of admission (KI group) versus those who did not (non-KI group). Prespecified subgroup analyses were performed based on the presence of the diagnosis of Graves' disease.
RESULTS
Among 3,188 eligible patients, 2,350 received KI within two days of admission. The crude in-hospital mortality was 6.1% (143/2,350) in the KI group and 7.8% (65/838) in the non-KI group. After adjusting for potential confounders, KI use was not significantly associated with in-hospital mortality (odds ratio [OR] for KI use, 0.91; 95% confidence interval [CI], 0.62-1.34). In patients with the diagnosis of Graves' disease, in-hospital mortality was lower in the KI group than in the non-KI group (OR, 0.46; 95% CI, 0.25-0.88). No significant difference in in-hospital mortality was observed in patients without the diagnosis of Graves' disease (OR, 1.11; 95% CI, 0.67-1.85). Length of stay was shorter (subdistribution hazard ratio, 1.15; 95% CI, 1.05-1.27), and total hospitalization costs were lower (OR, 0.92; 95% CI, 0.85-1.00) in the KI group compared with the non-KI group.
CONCLUSION
Our findings suggest that KI may reduce in-hospital mortality among patients hospitalized for thyroid storm with Graves' disease.
PubMed: 38546426
DOI: 10.1210/clinem/dgae187 -
Cureus Nov 2023Graves' disease is an autoimmune disorder characterized by thyroid-stimulating antibodies that can potentially lead to thyrotoxicosis, goiter, skin disease, and eye... (Review)
Review
Graves' disease is an autoimmune disorder characterized by thyroid-stimulating antibodies that can potentially lead to thyrotoxicosis, goiter, skin disease, and eye disease. Available treatment options for Graves' disease include management with antithyroid drugs (ATDs), thyroid ablation with radioactive iodine (RAI), and surgical thyroid gland removal. For individuals unable to reach a normal thyroid hormone level, promptly considering a thyroidectomy is essential. Preoperative strategies to achieve a euthyroid state prevent thyroid storms and minimize postoperative complications and are therefore crucial. While variations in professional guidance exist, this review focuses on standard medical interventions as well as compares respective guidelines set forth by the American Thyroid Association, the European Thyroid Association, the American Association of Clinical Endocrinology, and the American Association of Endocrine Surgeons. There is consensus among these organizations underscoring the importance of rendering patients euthyroid prior to surgery and the use of ATDs. Most guidelines recommend screening for vitamin D deficiency as well as endorse thyroidectomy as the preferred treatment option for hyperthyroidism with skilled surgeons. Nevertheless, discrepancies do become apparent in aspects such as potassium iodide (SSKI) course duration and preoperative dexamethasone administration. By understanding these differing approaches, healthcare professionals can more effectively manage Graves' disease prior to surgery, resulting in improved patient outcomes and enhanced surgical success.
PubMed: 38046703
DOI: 10.7759/cureus.48156 -
Heliyon Jul 2023In this study, we have developed a new ultrasonic synthesis method of dibenzoepines using olanzapine and quetiapine, which are well-known drugs for the treatment of...
In this study, we have developed a new ultrasonic synthesis method of dibenzoepines using olanzapine and quetiapine, which are well-known drugs for the treatment of schizophrenia and bipolar disorder. The method is based on the -alkylation reaction of the piperazine fragment in tricyclic compounds with methyl iodide or 2-(2-chloroethoxy)ethanol as the alkylating agent, respectively. The synthesis reactions were carried out in an ultrasonic bath with solvents such as acetonitrile or dimethylformamide in the presence of potassium or sodium carbonate or sodium hydroxide and metal-free, ecological phase transfer catalyst at a temperature of 40-50 °C. This allowed us to obtain olanzapine in 1 h (Y = 67%), and quetiapine in 3 h (Y = 72%). An ultrasonic reactor (Qsonica Q700) was used in the synthesis of olanzapine and made it possible to shorten the reaction time to 10 min and obtain 90% yield with very high purity. The developed method allows obtaining compounds in mild conditions and in a short time, thanks to which the process is more ecological than others described in the literature.
PubMed: 37539205
DOI: 10.1016/j.heliyon.2023.e18319 -
Chemical Research in Toxicology Jul 2023Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature....
Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I > Br > F). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized OH and singlet oxygen (O) production over no-salt controls. Considering the relatively high levels of Na, K, and Cl ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons .
Topics: Humans; Chlorides; Sodium Chloride; Singlet Oxygen; Reactive Oxygen Species; Salts; Dermatitis, Phototoxic; Anthracenes; DNA
PubMed: 37347986
DOI: 10.1021/acs.chemrestox.2c00235 -
Medicina (Kaunas, Lithuania) Nov 2023This prospective, comparative, double-cohort study aimed to compare the efficacy of silver diamine fluoride and potassium iodide (38% SDF+KI; Riva Star) with sodium...
This prospective, comparative, double-cohort study aimed to compare the efficacy of silver diamine fluoride and potassium iodide (38% SDF+KI; Riva Star) with sodium fluoride varnish (5% NaF; Duraphat) in hypersensitive carious lesions in primary teeth to evaluate caries arrest and hypersensitivity relief. : This study included thirty 2-5-year-olds (mean age = 3.67 ± 1.06 years; 16 males and 14 females) who required a desensitizing treatment for hypersensitive carious defects with visible dentin. A total of 15 of the participants were consecutively allocated to treatment with 5% NaF, and they were further compared to an equal number of participants treated with 38% SDF+KI solutions ( = 15). The treatments were performed following clinical evaluation of caries activity using the International Caries Classification and Management System (ICCMS) and the Bjørndal criteria (score of 0-9). Parental-reported hypersensitivity was evaluated using a visual analogue scale (0-10 = no to severe pain). : Clinical variables were evaluated at baseline and three months after treatment. Thereafter, a significant decline in hypersensitivity/pain led to lower final scores in the Riva Star group (0.40 ± 1.12, = 0.002) than in the Duraphat group (1.40 ± 2.20, = 0.004). The caries arrest effect was significantly higher in the Riva Star group (86.7%) compared to the Duraphat group three months after treatment (13.3%, < 0.001). In both groups, there were no statistically significant differences in the children's behavior before, during, and after treatment. : Ultimately, with both fluoride therapies reducing hypersensitivity/pain significantly, treatment with 38% SDF+KI was clearly more effective in caries arrest than 5% NaF varnish after a 3-month period.
Topics: Male; Child; Female; Humans; Child, Preschool; Fluorides; Cariostatic Agents; Cohort Studies; Prospective Studies; Tooth, Deciduous; Pain; Dental Caries
PubMed: 38004091
DOI: 10.3390/medicina59112042 -
Prostaglandins & Other Lipid Mediators Jun 2024Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data...
BACKGROUND
Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that 2-IHDA inhibits several thyroid parameters and it has been postulated as intermediary on the action of iodide function.
OBJECTIVE
To explore different mechanisms involved during the involution of the hyperplastic thyroid gland of Wistar rats towards normality induced by 2-IHDA.
METHODS
Goiter was induced by the administration of MMI for 10 days, then the treatment was discontinued and Wistar rats were injected with 2-IHDA or KI.
RESULTS
During involution, 2-IHDA treatment reduced PCNA expression compared to spontaneous involution. KI treatment caused an increase of Caspase-3 activity and TUNEL-positive cells. In contrast, 2-IHDA failed to alter this value but induced an increase of LC3B expression. KI but not 2-IHDA led to an increase in peroxides levels, catalase and glutathione peroxidase activity.
CONCLUSIONS
We demonstrated that 2-IHDA, in contrast to iodide, did not lead to an increase in oxidative stress or apoptosis induction, indicating that the involution triggered by 2-IHDA in Wistar rats, is primarily due to the inhibition of cell proliferation and the induction of autophagy.
Topics: Animals; Autophagy; Rats, Wistar; Goiter; Rats; Aldehydes; Thyroid Gland; Apoptosis; Oxidative Stress; Potassium Iodide; Caspase 3; Cell Proliferation; Male; Proliferating Cell Nuclear Antigen; Female
PubMed: 38346574
DOI: 10.1016/j.prostaglandins.2024.106819 -
Journal of Trace Elements in Medicine... Sep 2023We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid...
OBJECTIVE
We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats.
METHODS
Pregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system.
RESULTS
High iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = -0.909, p = 0.012; r = -0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = -0.917, p = 0.01; r = -0.859, p = 0.028; r = -0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = -0.990, p = 0.0002) and Txnrd2 expression (r = -0.979, p = 0.001; r = -0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased.
CONCLUSION
In addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.
Topics: Pregnancy; Female; Animals; Rats; Thyroid Gland; Iodides; Lactation; Thyroid Hormones; Iodine; Thioredoxin Reductase 2
PubMed: 37506535
DOI: 10.1016/j.jtemb.2023.127267 -
Ultrasonics Sonochemistry Dec 2023The removal of per- and polyfluoroalkyl substance (PFAS) pollution from the environment is a globally pressing issue, due to some PFAS' recalcitrant, bioaccumulative,...
The removal of per- and polyfluoroalkyl substance (PFAS) pollution from the environment is a globally pressing issue, due to some PFAS' recalcitrant, bioaccumulative, and carcinogenic nature. Destruction via ultrasonic waves (sonolysis) is a promising contender for industrialisation due to; moderate power consumption, applicability to several PFAS and sample types, and limited by-products. Liquid flow rate through an ultrasonic reactor can affect the size, shape, and spatial distribution of ultrasonic cavities and hence their chemical activity. Such effects have not been studied during PFAS sonolysis, and temporal effects have not been studied much beyond the reactant concentration. Here, the effects of varying recirculating flow rate on the ultrasonic defluorination of perfluorooctane sulfonic acid (PFOS) and implications for industrial scale up are presented. Under the ultrasonic power (200 W L, 2.27 W cm) and frequency (410 kHz) used, flow rates of 79 and 214 ml min enhanced defluorination up to 14 % during 30 min of treatment. However, these effects were temporal and most significant in the initial minutes of treatment. This indicated a dynamic bubble size distribution which stabilised after around 15 min. Defluorination rates of PFOS were compared with measured potassium iodide dosimetry, calorimetry, sonoluminescence (SL), and sonochemiluminescence (SCL). Flow rates which enhanced defluorination correlated moderately with enhanced SCL and negatively impacted SL, calorimetry, and dosimetry. Effects were attributed to perturbed cavity surfaces, leading to asymmetric cavity collapse, and the possibility of enhanced solvated electron production/interaction. SL, SCL, dosimetry, and calorimetric measurements were also temporal, and each showed different times to equilibrate. Flow rates of 439 and 889 ml min returned all sonochemical measurements to the levels without flow, likely due to continued collapse temperature quenching by furthered bubble asymmetry. Flow also enhanced reactor cooling, which is significant for industrial temperature control. The pump energy consumed was small (≈1.9 %) compared to that of the amplifier and chiller, hence, PFOS defluorination was more cost-effective using flow. However, the effect may be limited for the longer treatment times needed for environmental remediation.
PubMed: 38039593
DOI: 10.1016/j.ultsonch.2023.106667 -
Clinical Oral Investigations Dec 2023To investigate the response of pulp cells to the application of silver diamine fluoride (SDF) and potassium iodide (KI) on demineralized dentin.
OBJECTIVES
To investigate the response of pulp cells to the application of silver diamine fluoride (SDF) and potassium iodide (KI) on demineralized dentin.
MATERIALS AND METHODS
The occlusal surfaces of human dentin discs (0.4 mm thick) with similar permeability were subjected to an artificial caries protocol, and then the discs were adapted into artificial pulp chambers. MDPC-23 cells were seeded on the healthy pulp dentin surface, while the demineralized surface was treated with SDF, KI, SDF + KI, or hydrogen peroxide (positive control-PC) (n = 8). The negative control (NC) received ultrapure water. After 24 h, cell viability (alamarBlue) and morphology (SEM) were evaluated. The extracts were then applied to new MDPC-23 cells seeded in culture plates to assess their viability and the formation of mineralized nodules (MN; Alizarin Red) after seven days. The data were analyzed using one-way analysis of variance/Tukey or Games-Howell tests (α = 5%).
RESULTS
SDF and PC significantly reduced the viability of cells seeded on discs (45.6% and 71.0%, respectively). Only cells treated with SDF or PC detached from the dentin substrate, while the remaining cells showed altered morphology. Cells in contact with extracts showed less reduction in viability, but it was still more toxic compared to NC. Only PC reduced MN deposition. SDF + KI or KI alone did not affect the cell response.
CONCLUSIONS
SDF applied alone showed a mild to moderate transdentinal cytotoxic effect on pulp cells. However, the combination of SDF + KI reduced the cytotoxic effects. Both materials used alone or in combination did not affect the mineralization ability of pulp cells.
CLINICAL RELEVANCE
Besides improving esthetic results, associating potassium iodide with silver diamine fluoride may reduce the transdentinal cytotoxic effects of this cariostatic agent on pulp cells.
Topics: Humans; Potassium Iodide; Dental Pulp Cavity; Dental Caries Susceptibility; Dentin; Esthetics, Dental; Fluorides, Topical; Dental Caries; Quaternary Ammonium Compounds
PubMed: 37853265
DOI: 10.1007/s00784-023-05320-8