HYPOTHYROIDISM INCREASES EXPRESSION OF STERILE INFLAMMATION PROTEINS IN RAT HEART TISSUE.

PURPOSE: In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. METHODS: Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. RESULTS: In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. CONCLUSION: Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

Development of an intranasal formulation containing indomethacin and xylometazoline for rhinosinusitis treatment.

OBJECTIVE: Use of the nasal route of drug administration dates back many years and is used both to achieve topical treatments and to allow systemic absorption. The objective was to develop a formulation with novel features which enhance prolonged contact with the nasal and sinusal lining, since this should increase any therapeutic benefit. The anti-inflammatory drug selected was indomethacin, which was combined with xylometazoline, an effective nasal decongestant agent. MATERIALS AND METHODS: 28 Sprague-Dawley rats were used. They were then allocated at random to one of the four groups of equal size. All rats received a nasal application of 50mL of the platelet-activating factor solution at a concentration of 16 µg/mL and had induced rhinosinusitis. Indomethacin or xylometazoline HCl or both were dissolved in the oily phase of the solution and then a magnetic stirrer was used to homogenize the solution for 60 min at room temperature. All the O/W solutions exhibited stability and remained at neutral pH for the entire duration of the experiment. The only intervention was application of inactive 0.9% saline in group 1. The intervention was nasal application of xylometazoline and indomethacin in the combined formulation in group. The intervention was nasal application of xylometazoline only in group 3. The intervention was nasal application of indomethacin only in group 4. RESULTS: For the animals in group 1 (the controls), the mucosa had sustained a significant level of damage and the vessels were highly congested. Inflammatory cells were extensively infiltrating the mucosa. (Figure 1 - A1, 2, 3). In group 2, by contrast, the vessels were hardly congested and there were very few infiltrates. The epithelium appeared completely intact (Figure 1 - B1, 2, 3). Furthermore, when groups 1 and 2 were compared in terms of congested vessels, inflammatory cellular infiltrates and injury to the epithelium, the differences reached statistical significance, with p-values of <0.01, >0.001 and <0.001, respectively. Comparison of groups 2 and 4 with the control group also revealed statistically significant differences in terms of cellular infiltrates (p<0.001) and damage to the epithelium (p<0.001). For the degree of congestion of the vessels, however, the difference between groups was not at the level of statistical significance (p<0.071). Groups 3 and 4 differed at a statistically significant level in terms of degree of congested vessels, cellular infiltrates, and damage to the epithelium (p<0.025 and p<0.001). The sections from rats in groups 2 and 3 had a lower degree of congested vessels, which may be due to the actions of xylometazoline. CONCLUSIONS: In the future, topically applied intranasal NSAIDs will be valuable formulations. Innovative types of formulation, such as those demonstrating thixotropic behavior, permit the agent to remain in prolonged contact with the nasal and sinusal lining. Alongside increased efficacy, these preparations will also improve the side effect profile of NSAIDs, largely eliminating systemic effects.

An evaluation of the efficacy of indomethacin in experimentally induced acute sinusitis in rats.

OBJECTIVE: We evaluated how efficacious indomethacin, at two different doses, is in the treatment of an experimental model of sinusitis in rats. MATERIALS AND METHODS: Twenty-one Wistar albino rats (all male) were sorted at random into one of three groups: 1st group (n=7) was placebo. 2nd group (n=7). These rats had sinusitis induced experimentally, following indomethacin 3 mg/kg, 5 days was administered to them. 3rd group (n=7). These rats had sinusitis induced experimentally, following indomethacin 6 mg/kg, 5 days was administered to them. The animals' sinonasal mucosae were examined histopathologically by standard light microscopy. RESULTS: Experimental sinusitis was observed in the 2nd and 3rd groups, but not in the rats administered a placebo. Although the inflammatory features of sinusitis were found to be significantly decreased in the animals administered indomethacin 3 mg/kg (the 2nd group), this anti-inflammatory effect was even greater in the 3rd group, where indomethacin 6 mg/kg had been administered. Indomethacin at either dose was superior to placebo in reducing inflammatory features of sinusitis. CONCLUSIONS: Topical use of indomethacin nasal drops decreased the inflammatory features in experimentally induced acute sinusitis. Moreover, a higher dose of indomethacin (6 mg/kg) was more efficacious than a lower dose (3 mg/kg). The present study is valuable as an initial step in showing the need to undertake human trials to see the effect of indomethacin nasal drops on sinusitis in humans. In acute rhinosinusitis, the use of topical anti-inflammatory drops may help to decrease the symptoms and may be used adjunctively with antibiotic treatment.

Posterior translacrimal approach to the maxillary sinus.

BACKGROUND: This study aimed to compare the view into the maxillary sinus using the posterior translacrimal approach compared with grade 3 antrostomy. METHODS: Grade 3 antrostomy followed by a posterior translacrimal approach was performed on four cadavers. The maximum intramaxillary view was documented endoscopically guided by electromagnetic navigation. Representative screenshots were evaluated in a blinded manner by three independent sinus surgeons. In addition, a prospective investigation of specific complications in the post-operative course of consecutive patients was performed. RESULTS: In the cadaver study, the posterior translacrimal approach provided a significantly better view into the maxillary sinus compared with grade 3 antrostomy. In the clinical study, only 1 out of 20 patients reported on a minor problem with lacrimal drainage at 6 months. CONCLUSION: The posterior translacrimal approach to visualising the maxillary sinus should be considered a strong alternative to more radical techniques.