Effect of submucosal cryotherapy compared with steroids and NSAIDs injections on Substance P and Interleukin 6 pulpal release in experimentally induced pulpal inflammation in rabbits.

OBJECTIVE: To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6 release in experimentally induced pulpal inflammation in rabbits' molar teeth. METHODOLOGY: Fifteen rabbits were randomly classified into 3 groups according to the submucosal injection given: cold saline, dexamethasone sodium phosphate, and diclofenac sodium. A split-mouth design was adopted, the right mandibular molars were experimental, and the left molars served as the control without injections. Intentional pulp exposures were created and left for 6 hours to induce pulpitis. Pulpal tissue was extracted and examined for SP and IL-6 levels using ELISA. Within each group, the level of cytokines released was measured for both control and experimental groups for intragroup comparison to determine the effect of injection. The percentage reduction of each mediator was calculated compared with the control side for intergroup comparison then the correlation between SP and IL-6 levels was analyzed using Spearman's rank order correlation coefficient. Statistical analysis was performed, and the significance level was set at p<0.05. RESULTS: Submucosal cryotherapy, dexamethasone sodium phosphate, and diclofenac sodium significantly reduced SP and IL-6 pulpal release. Submucosal cryotherapy significantly reduced SP more than and IL-6 more than dexamethasone sodium phosphate and diclofenac sodium. Pulpal reduction of SP and IL-6 showed a strong positive significant correlation. CONCLUSIONS: Submucosal cryotherapy reduces the pulpal release of SP and IL-6 and could be tested as an alternative to premedication to potentiate the effect of anesthesia and control postoperative endodontic pain.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

Intrathyroid injection of dexamethasone inhibits Th2 cells in Graves disease

ABSTRACT Objective Intrathyroid injection of dexamethasone (IID) was used for decrease the relapse rate of hyperthyroidism in the treatment of Graves' disease (GD), but the mechanism is still unclear. We aimed to explore the effect of IID on T help (Th)1/Th2 cells and their chemokine in patients with GD. Subjects and methods A total of 42 patients with GD who were euthyroidism by methimazole were randomly divided into IID group (n = 20) and control group (n = 22). Thyroid function and associated antibody, Th1/Th2 cells proportion, serum CXCL10 and CCL2 levels, and CXCR3/CCR2 mRNA expression in peripheral blood mononuclear cells before and after 3-month IID treatment were tested by chemiluminescence assay, Flow cytometry, ELISA, and real-time PCR, respectively. Thyroid follicular cells were stimulated by IFN-γ and TNF-α and treated with dexamethasone in vitro. CXCL10 and CCL2 levels in supernatant were determined. Results After 3-month therapy, the proportion of Th2 cells and serum CCL2 levels, as well as TPOAb, TRAb levels and thyroid volume decreased in IID group (p < 0.05). However, the proportion of Th1 and CXCL10 levels had no change in IID group and control (p > 0.05). The CXCR3/CCR2 ratio had no change in both groups (p > 0.05). Conclusion IID therapy could inhibit peripheral Th2 cells via decreasing CCL2 level in peripheral blood, and this result partly explain the effects of IID therapy on prevention of relapse of GD. Arch Endocrinol Metab. 2020;64(3):243-50

Preliminary characterization of dexamethasone-loaded cross-linked hyaluronic acid films for topical ocular therapy.

The aim of this work was to design and characterize cross-linked hyaluronic acid (HA)-itaconic acid (IT) films loaded with dexamethasone sodium phosphate salt (DEX) for topical therapy of inflammatory ocular surface diseases. Films were chemically cross-linked with polyethylene glycol diglycidyl ether (PEGDE), then physical and mechanical characterization by stress-strain, X-ray diffraction, X-ray fluorescence spectrometry and swelling assays was conducted. A sequential in vitro therapeutic efficacy model was designed to assess changes in interleukin (IL)-6 production in an inflamed human corneal epithelial (HCE) cell line after film exposure. Changes in cell proliferation after film exposure were assessed using the alamarBlue(®) proliferation assay. Experimental findings showed desirable mechanical properties and in vitro efficacy to reduce cell inflammation. A moderately decreased proliferation rate was induced in HCE cells by DEX-loaded films, compared to commercial DEX eye drops. These results suggest that DEX and HA have opposite effects. The sequential in vitro therapeutic efficacy model arises as an efficient tool to study drug release from delivery systems by indirect measurement of a biological response.

Proteomics of endometrial fluid after dexamethasone treatment in mares susceptible to endometritis.

Corticotherapy is a common treatment in mares susceptible to endometritis. Isoflupredone improves pregnancy rates and affects the protein profile of endometrial fluid in comparison to untreated mares. Dexamethasone decreases postbreeding fluid accumulation and uterine edema; however, its effects on the protein profile of the endometrial fluid have not yet been studied. The aim of the present study was to verify the effect of dexamethasone on the protein profile of endometrial fluid, in the presence or absence of infection, from mares susceptible to persistent postbreeding endometritis. Nine susceptible mares aged between 7 and 18 years were used. After checking for signs of estrus, mares were subjected to four treatments: C: mares received no treatment and served as control; D: mares received 40-mg dexamethasone at breeding, with collection of samples after 6 hours; I-6 and I-24: intrauterine infusion of 1 × 10(9)Streptococcus zooepidemicus/mL and samples collected after 6 and 24 hours; I/D-6 and I/D-24: intrauterine infusion of 1 × 10(9)S zooepidemicus/mL and 40-mg dexamethasone, collecting the sample after 6 and 24 hours. All mares were subjected to all treatments. Samples were collected and subjected to two-dimensional electrophoresis and mass spectrometry for the identification of relevant protein spots. Corticotherapy altered the protein profile of the endometrial fluid of susceptible mares, characterized by an increase and/or decrease in the optical density of inflammatory acute-phase proteins. We conclude that the use of dexamethasone in mares with and without infection alters the protein profile of endometrial fluid of susceptible mares.

The Idealized Brazilian Health System versus the real one: contributions from the nursing field / O Sistema Único de Saúde idealizado versus o realizado: contribuições da Enfermagem / El Sistema Único de Salud idealizado versus el realizado: contribuciones de la Enfermería

OBJECTIVE: to identify the perceptions of professionals working in a facility connected with the Brazilian Unified Health System - SUS in regard to what they know, think and talk about public health policy. METHOD: this exploratory-descriptive study with a qualitative nature was conducted with 28 professionals working in a facility connected with the SUS. Data were collected through interviews with guiding questions and analyzed through the thematic content analysis technique. RESULTS: coded and interpreted data resulted in three thematic axes: The SUS - perfect web that does not work in practice; The recurrent habit of complaining about the SUS; The need to rethink the way of thinking about, acting in and managing the SUS. CONCLUSION: the professionals working for the SUS are aware of the principles and guidelines that govern the Brazilian health system, however, they reproduce a dichotomous and linear model of conception and practice strongly linked to the thinking of society in general. .

OBJETIVO: conhecer a percepção de profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde sobre o que sabem, pensam e falam dessa política pública de saúde. MÉTODO: trata-se de estudo exploratório-descritivo, de caráter qualitativo, realizado com 28 profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde. Os dados foram coletados por meio de entrevistas com questões norteadoras e analisados pela técnica de análise de conteúdo temática. RESULTADOS: os dados codificados e interpretados resultaram em três eixos temáticos: Sistema Único de Saúde - teia perfeita que não funciona na prática; o recorrente hábito de reclamar do Sistema Único de Saúde; a necessidade de repensar o modo de pensar, atuar e gerir o Sistema Único de Saúde. CONCLUSÃO: os profissionais que atuam no Sistema Único de Saúde têm conhecimento dos princípios e diretrizes que regem o sistema de saúde nacional, no entanto, reproduzem um modelo de concepção e atuação dicotômico, pontual e linear ainda fortemente vigente no pensar da sociedade em geral. .

OBJETIVO: conocer la percepción de profesionales que actúan en una institución que tiene convenio con el Sistema Único de Salud - SUS sobre lo que saben, piensan y hablan de esta política pública de salud. MÉTODO: se trata de un estudio exploratorio descriptivo, de carácter cualitativo, realizado con 28 profesionales que actúan en una institución que tiene convenio con el SUS. Los datos fueron recolectados por medio de entrevistas con preguntas orientadoras y analizados con la técnica de análisis de contenido temático. RESULTADOS: los datos codificados y interpretados resultaron en tres ejes temáticos: SUS - red perfecta que no funciona en la práctica; el recurrente hábito de reclamar del SUS; y la necesidad de repensar el modo de pensar, actuar y administrar el SUS. CONCLUSIÓN: los profesionales que actúan en el SUS tienen conocimiento de los principios y directrices que gobiernan el sistema de salud nacional, sin embargo, reproducen un modelo de concepción y actuación dicotómico, puntual, linear y además fuertemente vigente en el pensar de la sociedad en general. .

Morphometric evaluation of the fetal rat liver after maternal dexamethasone treatment: effect on the maturation of erythroid and megakaryocytic cells.

BACKGROUND: During pregnancy, glucocorticoids are frequently used to accelerate fetal lung maturation in preterm delivery. However, prenatal administration of glucocorticoids has been shown to affect organs such as fetal liver, an important hematopoietic organ during fetal development. OBJECTIVE: The aim of this study was to document the qualitative and quantitative changes in erythroid and megakaryocytic cell populations found in fetal livers as well as the hematology profile in neonates after maternal glucocorticoid treatment in rats. METHODS: Pregnant female Wistar rats were treated with dexamethasone 21-phosphate from days 13 to 16 of gestation. On the 17th day of pregnancy, the fetuses were collected and their livers processed for light and transmission electron microscopy. Glycol methacrylate-embedded sections were stained with PAS to determine the erythroblast and megakaryocytic cell frequencies. Fetal liver pieces embedded in Spurr resin were analyzed by transmission electron microscopy for morphologic changes. A standard hematology profile was evaluated in neonatal rats. RESULTS: In the fetuses from treated dams, the total cell number of erythroid cells in livers was significantly reduced compared to control fetuses (P < .001), but erythroblasts did not present ultrastructural abnormalities. The degree of maturation in the megakaryocyte series tended to be increased. In neonates, there were elevated numbers of nucleated RBCs (P = .002), along with a higher HCT and HGB (P = .02). In addition, the platelet concentration was also significantly increased (P < .007). CONCLUSION: These results suggest that maternal dexamethasone treatment has quantitative effects on erythroid and megakaryocytic cells in fetal liver and the neonatal hematology profile in rats.

Local drug delivery system: inhibition of inflammatory angiogenesis in a murine sponge model by dexamethasone-loaded polyurethane implants.

Implants are defined as controlled sustained release delivery systems of therapeutic agents incorporated or dispersed into a polymeric carrier. These systems can be implanted in specific organs and delivered by the therapeutic agents at the target site to treat various pathological processes. In the present study, the effects of dexamethasone-loaded polyurethane implants [PU ACT (dexamethasone acetate) implants] on inflammatory angiogenesis in a murine sponge model were investigated. PU ACT implants were inserted into nonbiocompatible sponges, used as a framework for fibrovascular tissue growth, and implanted into subcutaneous tissue located on the back of mice. After 7 days of implantation, the implant system was collected and processed for the assessment of hemoglobin (Hb; vascular index), myeloperoxidase (MPO), and N-acetyl-ß-D-glucosaminidase (NAG; inflammatory enzymes activities) and collagen content. ACT released from the polymeric implants provided a significant decrease in the neovascularization in the sponge (Hb content). PU ACT implants provided no effects on neutrophil infiltration (MPO activity) but macrophage recruitment was affected by the glucocorticoid delivered by implants (NAG activity). ACT released from implants was able to reduce the collagen deposition. The qualitative histological findings corroborated with the measured biochemical parameters. These local drug delivery systems derived from polyurethane efficiently modulated the key components of inflammation, angiogenesis, and fibrosis induced by sponge discs in an experimental animal model.

Evidences of osteoporosis improvement in Wistar rats treated with Ginkgo biloba extract: a histomorphometric study of mandible and femur.

This study was aimed at investigating the anti-osteoporotic effects of the extract of Ginkgo biloba (EGb) in glucocorticoid-induced-osteoporosis. A significant reduction was observed in the percentage of the bone of the osteoporosis group in both the mandible and femur. The EGb group treated with 28 and 56 mg/Kg showed a significant increase in the percentage of trabecular bone (PTB) of the femur. The percentage of the alveolar bone of the mandible (PAB) had a significant increase with all doses of EGb. The treatment with EGb significantly reversed the loss of the PAB of the mandible and of the PTB of the femur.

The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment.

AIM: Glucocorticoid administration induces insulin resistance (IR) and enhances islet mass and insulin secretion in rodents and humans. Here, we analysed whether these effects are still present after the interruption of dexamethasone treatment. METHODS: Adult Wistar rats were distributed into CTL (daily injection of saline for five consecutive days), DEX (daily injection of 1 mg kg(-1) body wt of dexamethasone for five consecutive days) and DEX(10) (5 days of dexamethasone treatment, followed by a period of 10 days without dexamethasone). RESULTS: In vivo experiments indicated that the marked hyperinsulinemia found in DEX rats during fasting and fed states was normalized in the DEX(10) group. Furthermore, the IR and glucose intolerance observed in DEX were restored in DEX(10) rats. Islets from DEX rats secreted more insulin in response to increasing concentrations of glucose and other metabolic and non-metabolic stimuli, compared with that in the CTL group. The insulin secretion for the most compounds studied returned to CTL values in DEX(10) islets. Increased insulin secretion correlated well with the augmentation in ß-cell proliferation and mass in DEX rats, and these morphological alterations were normalized in islets from DEX(10) rats. In parallel, the increased levels of proteins involved in ß-cell proliferation such as Cd2 and Cdk4 observed in DEX islets were also normalized in DEX(10) islets. CONCLUSION: These data strongly support the view that almost all the morphophysiological alterations induced by dexamethasone in the endocrine pancreas are reverted after discontinuation of the treatment. This information is important, considering the frequent use of glucocorticoids in humans.

Controlled release of dexamethasone acetate from biodegradable and biocompatible polyurethane and polyurethane nanocomposite.

Polyurethanes and polyurethane nanocomposites can be applied to control the release of drugs previously incorporated into these materials. In this study, dexamethasone acetate (ACT) was incorporated into biodegradable and biocompatible polyurethane and polyurethane containing montmorillonite nanoparticles. Fourier transform infrared spectroscopic technique showed no strong interactions between drug and polymers. Data obtained from X-ray diffraction and small angle X-ray scattering indicated that the incorporation of ACT did not disturb the polymer morphology, but montmorillonite led to a less defined phase separation between hard and soft segments of polyurethane. The in vitro release studies demonstrated that nanoparticles increased the rate of ACT release possibly because these particles have a hydrophilic surface that increases the absorption of water and accelerates the hydrolysis of the polymer. The in vivo short-term biocompatibility studies demonstrated adequate interfacial interaction between polyurethane and subcutaneous tissue and a discreet inflammatory response which was completely resolved in 14 days.

Electromotive drug administration for treatment of therapy-refractory overactive bladder.

PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA) as an alternative technique in patients with chronic overactive bladder in terms of improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A total of 72 patients with therapy-refractory overactive bladder according to the ICS (International Continence Society) definition, were treated by EMDA. The regimen consisted of three treatment cycles, each with 3 instillations at 2-week intervals. The solution instilled consisted of 100 mL 4% lidocaine, 100 mL distilled water, 40 mg dexamethasone, and 2 mL epinephrine. Peri-interventionally, a urine test and close circulatory monitoring were performed. All women underwent urodynamic testing and cystoscopy and kept a voiding diary. A comprehensive history was obtained, a quality of life questionnaire administered, and a gynecologic examination performed before initiation of therapy. The women underwent follow-up at 12 months after the end of therapy. RESULTS: The patients had a mean age of 63 (+/- 11.2) years. Bladder capacity improved significantly by 109 mL (+/- 55 mL) in 51 (71%) patients (p = 0.021). The number of micturitions/day decreased significantly to 7 (+/- 2) (p = 0.013). Quality of life was improved in 54 patients (75%); p = 0.024) and sexuality in 39 (54%); p = 0.020). CONCLUSIONS: The results suggest that EMDA can improve both quality of life and sexuality in patients with therapy-refractory chronic overactive bladder.

Electromotive drug administration for treatment of therapy-refractory overactive bladder

PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA) as an alternative technique in patients with chronic overactive bladder in terms of improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A total of 72 patients with therapy-refractory overactive bladder according to the ICS (International Continence Society) definition, were treated by EMDA. The regimen consisted of three treatment cycles, each with 3 instillations at 2-week intervals. The solution instilled consisted of 100 mL 4 percent lidocaine, 100 mL distilled water, 40 mg dexamethasone, and 2 mL epinephrine. Peri-interventionally, a urine test and close circulatory monitoring were performed. All women underwent urodynamic testing and cystoscopy and kept a voiding diary. A comprehensive history was obtained, a quality of life questionnaire administered, and a gynecologic examination performed before initiation of therapy. The women underwent follow-up at 12 months after the end of therapy. RESULTS: The patients had a mean age of 63 (± 11.2) years. Bladder capacity improved significantly by 109 mL (± 55 mL) in 51 (71 percent) patients (p = 0.021). The number of micturitions/day decreased significantly to 7 (± 2) (p = 0.013). Quality of life was improved in 54 patients (75 percent); p = 0.024) and sexuality in 39 (54 percent); p = 0.020). CONCLUSIONS: The results suggest that EMDA can improve both quality of life and sexuality in patients with therapy-refractory chronic overactive bladder.

Physicochemical properties and dissolution studies of dexamethasone acetate-beta-cyclodextrin inclusion complexes produced by different methods.

Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug, and beta-cyclodextrin (betaCD) were obtained to improve the solubility and dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA was significantly increased in the presence of betaCD (33-fold) and was classified as A(L)-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation, freeze drying) and physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption and optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles of solid complexes were determined and compared with those DMA alone and their physical mixture, in three different mediums: simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4) and distilled water. The dissolution studies showed that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics. According to the results, the freeze-dried and kneaded products exhibited higher dissolution rates than the drug alone, in all the mediums.

Safety and pharmacokinetics of an intravitreal biodegradable implant of dexamethasone acetate in rabbit eyes.

The treatment of vitreoretinal diseases is limited and, nowadays, new drug delivery approaches have been reported in order to increase drug bioavailability. The objective of the current study was to determine the pharmacokinetic profile of a biodegradable dexamethasone acetate implant inserted into the vitreous of rabbits and to evaluate its potential signs of toxicity to the rabbits' eyes. The results showed that the intravitreous drug concentration remained within the therapeutic range along the 8-week period of evaluation. The system under study was not toxic to the normal rabbit retina, and no significant increase in intraocular pressure was observed.

Dexamethasone decreases plasma levels of the prochiral fenbendazole and its chiral and achiral metabolites in sheep.

1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.

A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children.

OBJECTIVE: To evaluate whether a single dose of intramuscularly administered dexamethasone acetate (IM Dex) was as safe and effective as a 5-day course of oral prednisone (PO Pred) in the treatment of young children with mild-moderate exacerbations of asthma. STUDY DESIGN: A prospective, randomized, investigator-blinded study was done in a tertiary care medical center in children (6 months to 7 years of age) who required corticosteroids to treat mild-moderate asthma exacerbations as outpatients. Patients were randomized to receive either a single dose of IM Dex ( approximately 1.7 mg/kg) or PO Pred ( approximately 2 mg/kg/d for 5 days). Clinical asthma score, behavioral changes, albuterol use, and tolerance of the medication were recorded in a home diary for 7 days. Cortisol/creatinine ratios on first morning void urine samples were obtained on day 14. The primary outcome measures were changes in clinical asthma score through day 5 and tolerance of the medication. RESULTS: Fifteen patients in the IM Dex group (mean age 37 months) and 17 in the PO Pred group (mean age 36 months) completed the study. Clinical asthma score improved significantly in both groups during the first 5 days of therapy, and no significant difference was seen in the rate of improvement between the 2 groups. Three children refused more than 75% of their prednisone doses, and another 4 missed 30% to 50% of the doses despite their parents' best efforts. The intramuscular injection caused no complications, and approximately 70% of parents in both groups stated that they would choose IM Dex to treat their child's next asthma exacerbation. CONCLUSION: In this group of children a single intramuscular injection of dexamethasone acetate was as effective as a 5-day course of PO Pred for the management of mild-moderate outpatient asthma exacerbations.