DMPP attenuates lipopolysaccharide-induced lung injury by inhibiting glycocalyx degradation through activation of the cholinergic anti-inflammatory pathway.

The study aimed to investigate the therapeutic potential of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), an agonist of nicotinic acetylcholine receptor (nAChR), in treating acute lung injury (ALI) induced by lipopolysaccharide (LPS). A murine ALI model was developed utilizing intraperitoneal injection of LPS. We evaluated the therapeutic efficacy of DMPP treatment in LPS-induced lung injury using various approaches, including pathohistological evaluation, appraisal of pulmonary edema, and measurement of inflammatory cytokine levels and their associated pathways within lung tissues. The gene chip data of LPS-induced acute lung injury mice were retrieved from the Gene Expression Omnibus (GEO) database for gene differential expression analysis and Gene Set Enrichment Analysis (GSEA) analysis. The impact of DMPP on glycocalyx shedding was assessed by measuring the expression levels of syndecan-1 (SDC-1) and matrix metalloproteinase-9 (MMP-9). DMPP treatment significantly improved pathomorphological changes and pathological lung injury scores in the LPS-induced ALI mouse model. The genes expressed differentially in the LPS-induced ALI group in GSE2411 were found to be involved in multiple processes, including the NF-κB signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, as well as the JAK-STAT signaling pathway. DMPP treatment effectively downregulated pro-inflammatory cytokines, suppressed the NF-κB signaling pathway, and effectively restrained the LPS-induced upregulation of MMP-9 and shedding of syndecan-1, thereby contributing to the preservation of endothelial glycocalyx and attenuation of endothelial barrier dysfunction. The administration of DMPP has been shown to confer protection against LPS-induced acute lung injury via a cholinergic anti-inflammatory pathway, which effectively inhibits endothelial glycocalyx degradation.

Isoalantolactone (IAL) Regulates Neuro-Inflammation and Neuronal Apoptosis to Curb Pathology of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.

Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). CONCLUSION: VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

Lugol's solution but not formaldehyde affects bone microstructure and bone mineral density parameters at the insertion site of the rotator cuff in rats.

BACKGROUND: This study aimed to investigate whether rodent shoulder specimens fixed in formaldehyde for histological and histomorphometric investigations and specimens stained using Lugol's solution for soft tissue visualization by micro-computed tomography (microCT) are still eligible to be used for bone architecture analysis by microCT. METHODS: In this controlled laboratory study, 11 male Sprague-Dawley rats were used. After sacrifice and exarticulation both shoulders of healthy rats were assigned into three groups: (A) control group (n = 2); (B) formaldehyde group (n = 4); (C) Lugol group (n = 5). Half of the specimens of groups B and C were placed in a 4% buffered formaldehyde or Lugol's solution for 24 h, whereas the contralateral sides and all specimens of group A were stored without any additives. MicroCT of both sides performed in all specimens focused on bone mineral density (BMD) and bone microstructure parameters. RESULTS: BMD measurements revealed higher values in specimens after placement in Lugol's solution (p < 0.05). Bone microstructure analyses showed increased BV/TV and Tb.Th values in group C (p < 0.05). Specimens of group C resulted in clearly decreased Tb.Sp values (p < 0.05) in comparison to the control group. Formaldehyde fixation showed minimally altered BMD and bone microstructure measurements without reaching any significance. CONCLUSIONS: MicroCT scans of bone structures are recommended to be conducted natively and immediately after euthanizing rats. MicroCT scans of formaldehyde-fixed specimens must be performed with caution due to a possible slight shift of absolute values of BMD and bone microstructure. Bone analysis of specimens stained by Lugol's solution cannot be recommended.

Percutaneous Coronary Intervention for Chronic Total Occlusion versus Percutaneous Coronary Intervention for Non-Complex Coronary Lesions: Is There a Different Impact on Thyroid Function?

OBJECTIVE: This study assessed whether high levels of iodide administered during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) differentially influenced thyroid function compared to PCI for non-complex coronary lesions. SUBJECTS AND METHODS: A total of 615 patients were enrolled in the study; 205 underwent elective PCI for CTO lesions (Group I) and 410 underwent elective PCI for non-complex lesions including non-CTO, non-bifurcation, non-calcified, and non-tortuous lesions (Group II). Patients were monitored for development of incidental thyroid dysfunction between 1 and 6 months after PCI. RESULTS: The patients in Group I were administered a median of 255 mL of contrast medium during PCI for CTO; a median of 80 mL was administered to the patients in Group II during non-complex PCI (p =0.001). Ten (5.4%) of the 186 euthyroid patients in Group I and 19 (5%) of the 379 eu-thyroid patients in Group II developed subclinical hyper-thyroidism (p = 0.854). However, 7 (50%) of the 14 subclinical hyperthyroid patients in Group I and only 3 (12%) of the 25 subclinical hyperthyroid patients in Group II developed overt hyperthyroidism (p = 0.019). CONCLUSION: In euthyroid patients, PCI for coronary CTO lesions did not increase the risk for subclinical hyperthyroidism when compared to PCI for non-complex coronary lesions. However, in patients with subclinical hyperthyroidism at baseline, PCI for coronary CTO lesions significantly increased the development of overt hyperthyroidism when compared to PCI for non-complex coronary lesions.

Sialoadenitis inducida por yoduro relacionada con angiograma coronario / Iodide-induced sialadenitis related to coronary angiogram

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Novel Drugs Implicated in Pigmented Purpuric Dermatoses.

We describe two cases of cutaneous eruptions of pigmented purpuric dermatoses (PPDs) arising after exposure to medications not previously reported in the literature as causing these reactions. Specifically, two women had biopsy-proven PPDs, one after exposure to an over-the-counter iodine supplement marketed as an extract from "Norwegian kelp," and the other after intraocular injections of pegaptanib, a vascular endothelial growth factor inhibitor. The eruption occurred shortly after beginning the medication and resolved upon discontinuation. This highlights the importance of considering over-the-counter and intraocular medications when assessing cutaneous eruptions that may be medication related, such as PPDs.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: An RCT.

BACKGROUND: The recommendation for enteral iodide intake for preterm infants is 30 to 40 µg/kg per day and 1 µg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. METHODS: A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks' gestation. Trial solutions (sodium iodide or sodium chloride; dose 30 µg/kg per day) were given within 42 hours of birth to the equivalent of 34 weeks' gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin, and thyroid-binding globulin were measured on 4 specific postnatal days. The primary outcome was neurodevelopmental status at 2 years of age, measured by using the Bayley Scales of Infant Development-III. The primary analyses are by intention-to-treat, and data are presented also for survivors. RESULTS: One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; motor composite score, 0.21, 95% CI -2.23 to 2.65; and language composite score, -0.05, 95% CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. CONCLUSIONS: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography.

BACKGROUND: Low-osmolar non-ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography (CT). METHODS: Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. RESULTS: Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.

What is the clinical value of negative predictive values of skin tests to iodinated contrast media?

BACKGROUND: Iodinated contrast media (ICM) can cause hypersensitivity reactions (HSR), yet data are scant about the negative predictive value (NPV) of ICM skin tests. OBJECTIVE: To determine the NPV of skin tests to ICM Methods: We enrolled 73 patients with a history of HSRs to ICM, 136 subjects with no previous exposure to ICM, and, as controls, 47 subjects who had previously tolerated ICM. All the subjects had skin tests with the culprit and/or alternative ICM and were later questioned as to whether they were reexposed and/or reacted to the skin-test-negative ICM. RESULTS: Sixty (82.2%) and 13 (17.8%) patients had a history of immediate HSR and those with a history of nonimmediate HSR, respectively. The sensitivity and specificity of the skin tests were 18% and 97%, respectively, in patients with immediate HSR and were 23% and 99%, respectively, in patients with nonimmediate HSR. Of a total of 237 subjects with negative skin test results, 207 (87.3%) were asked about further ICM administration; 158 (84.9%) confirmed subsequent use either with (n = 15 [9.4%]) or without premedication (n = 143 [90.6%]). Of the 143 individuals, 140 tolerated skin-test-negative ICMs but three (1.9%) reacted to ICMs (two with mild nonimmediate reactions, one with a grade 1 immediate reaction). Of 20 patients who had previous HSR to ICM, 17 tolerated further skin-test-negative ICM without premedication. The NPV of ICM skin tests, therefore, was 97% (95% confidence interval, 7599%). CONCLUSION: The NPV of skin tests with ICM was high. None of the reactions in patients who had negative skin test results were severe, which may reassure physicians who hesitate to perform further evaluations in patients with negative skin test results.

Iodide mumps following fistulogram in a haemodialysis patient.

Iodide mumps, or contrast-induced acute sialadenitis, is characterised by rapid, painless enlargement of the salivary glands, following the use of iodinated contrast dye. The underlying mechanism of this adverse reaction is not completely understood. It could be due to an idiosyncratic reaction or related to deposition of iodide in the ductal systems of the salivary glands causing blockage and inflammation. With increasing renal dysfunction, the elimination half-life of the iodine-containing contrast dye gets prolonged. The course of iodine-induced sialadenitis is usually benign, and rapid resolution of symptoms is expected without definite treatment. The symptomatic management includes treatment with a parenteral non-steroidal anti-inflammatory drug (NSAID), steroids and dialysis. However, the role of steroids has been found to be controversial in previously published case reports. Pancreatic mumps and transient thyroid dysfunction were also reported in patients following iodinated contrast administration; the aetiology of this is thought to be similar to iodide-induced sialadenitis.

Genes and environment as predisposing factors in autoimmunity: acceleration of spontaneous thyroiditis by dietary iodide in NOD.H2(h4) mice.

In the field of autoimmune thyroiditis, NOD.H2(h4) mice have attracted significant and increasing attention since they not only develop spontaneous disease but they present thyroiditis with accelerated incidence and severity if they ingest iodide through their drinking water. This animal model highlights the interplay between genetic and dietary factors in the triggering of autoimmune disease and offers new opportunities to study immunoregulatory parameters influenced by both genes and environment. Here, we review experimental findings with this mouse model of thyroiditis.

Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening.

AIM: To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy. METHODS: We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer. All patients were divided into two groups: a magnifying narrow band imaging group, and a lugol chromoendoscopy group, for comparison of adverse symptoms. Esophageal cancer screening was performed on withdrawal of the endoscope. The primary endpoint was a score on a visual analogue scale for heartburn after the examination. The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations, change in vital signs, total procedure time, and esophageal observation time. RESULTS: The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group (P = 0.004, 0.024, respectively, ANOVA for repeated measures). The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group. There was no significant difference between the two groups with respect to other vital sign. The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group (450 ± 116 vs 565 ± 174, P = 0.004, 44 ± 26 vs 151 ± 72, P < 0.001, respectively). CONCLUSION: Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy. Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically.

Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model.

Preliminary data show higher stricture rates after radiofrequency ablation (RFA) for early esophageal squamous neoplasia compared with Barrett's esophagus. We studied the effects of Lugol stain (LS) directly prior to RFA on stricture formation in squamous epithelium. Of 16 pigs, the distal half of the esophagus was LS, followed by circumferential RFA (single application 12 J/cm(2) ) in the unstained and stained esophagus. Pigs were euthanized at day 0 (n = 4), 3 (n = 4), or 28 (n = 8). Histology was evaluated in four areas: blank-control (no RFA, no LS), blank-RFA (no LS), LS+RFA, and LS-control (no RFA). Stenosis severity in LS+RFA and blank-RFA at 28 days was assessed by the ratio of the mucosal diameter at the RFA area to the diameter 2 cm proximal of this zone. Histology showed submucosal edema in 50% of LS+RFA versus 0% in blank-RFA. Severity and depth of inflammation (day 3) was equal in LS+RFA and blank-RFA. Severity and depth of fibrosis (day 28) appeared more severe in LS+RFA. Consequently, stenosis was present in 100% (LS+RFA) versus 12.5% (blank-RFA). The stenosis-severity ratio was 0.40 (interquartile range 0.29-0.45) in LS+RFA versus 0.73 (interquartile range 0.64-0.78) in blank-RFA (P = 0.012). Limitations of this study were the difference in uptake of LS between pigs and humans, the difference in esophageal anatomy between pigs and humans, and between the proximal and distal esophagus within pigs. In conclusion, in the porcine squamous esophagus, stenosis rate and severity after RFA increased when preceded by LS. LS may be contributing in the altered response of squamous epithelium to RFA as compared with Barrett's esophagus.

Fujinon intelligent color enhancement for the diagnosis of early esophageal squamous cell carcinoma and precancerous lesion.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma is a common malignant tumor in recent years, and the key for improving the survival rate is early diagnosis and treatment. Computed virtual chromoendoscopy with the Fujinon intelligent color enhancement (FICE) system was reported to improve visualization of neoplastic and non-neoplastic lesions in gastroscopy and colonoscopy. The purpose of this study was to evaluate the value of FICE in the diagnosis of early esophageal squamous cell carcinoma and precancerous lesions. MATERIALS AND METHODS: Two hundred fifty-seven patients with suspicious lesions of the esophagus were examined successively by FICE, magnifying FICE, Lugol chromoendoscopy, and magnifying Lugol chromoendoscopy in the hospital. The lesions and the intrapapillary capillary loop (IPCL, microvessels at the surface of esophageal carcinoma) were observed and compared with the pathologic diagnosis that was regarded as the golden standard. RESULTS: The positive rates of early esophageal squamous cell carcinoma were 92.6% and 88.9% as examined by FICE and Lugol chromoendoscopy (p>0.05), and 96.3% and 92.6% as examined by magnifying FICE and magnifying Lugol chromoendoscopy (p>0.05), respectively. The magnifying FICE could observe the IPCL of the esophagus clearly. Early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia were mainly type IV and type V. Low-grade intraepithelial neoplasia and esophagitis were type II and type III, and normal esophagus was type I; however, the observation of the IPCL by magnifying Lugol chromoendoscopy was not clear. CONCLUSION: Fujinon intelligent color enhancement and magnifying FICE are complements to Lugol chromoendoscopy and magnifying Lugol chromoendoscopy in the diagnosis of early esophageal lesions.

Jod-Basedow effect due to prolonged use of lugol solution-case report.

Graves' disease is the most common form of hyperthyroidism, accounting for 60-80% of all cases of thyrotoxicosis. If left untreated, it may lead to severe thyrotoxicosis with cardiovascular, ocular, psychiatric complication, and in extreme cases thyrotoxic crisis with a high mortality rate. We present the case of a 50-years-old woman diagnosed in another service with Graves' disease and treated for many years with antithyroid drugs (ATDs), admitted to our service for a relapse due to treatment discontinuation. The surgical treatment was planned and the preoperative preparation with Lugol solution was initiated. Due to a misunderstanding, the administration of iodine solution was extended for a period of about 30 days, thus generating the so-called Jod-Basedow effect, with the exacerbation of the manifestations of thyrotoxicosis and risk of thyroid storm. The patient received treatment with high ATDs doses, glucocorticoids, and beta-blockers, resulting in the progressive improvement of symptoms. She was discharged from hospital and given the risk of thyrotoxic crisis the surgery was postponed. After a month, the patient underwent thyroidectomy without preoperative preparation with iodine solution. The operative and postoperative courses were uneventful.

[Iodinated contrast media and iodine allergy: myth or reality?]. / Produits de contraste iodés et "allergie a l'iode" mythe ou réalité ?

The term "iodine allergy" is an old phrase that refers to a reaction to iodinated contrast media. After a brief review of definitions, pathophysiological mechanisms and risk factors of this clinical entity, management is urged immediate and delayed according to the most recent recommendations from the literature. We underline that iodine allergy, as such, does not really exist.