Effect of Selenium on Quantitative Structural Changes in Dexamethasone-Induced Immunodeficiency Rat Models.

Background: One of the major indices of immunodeficiency is lymphoid organ atrophy. Some trace elements are candidates for the treatment of this defect. These conditions may induce structural changes in the sub-components of lymphoid organs. Therefore, this study evaluated the effect of selenium on volumetric changes in dexamethasone (DEX)-induced lymphoid organ atrophy in an animal model. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, in September 2016 to September 2017. Thirty-two male rats were divided into four groups: Group I; control (normal saline, 0.5 mL/kg, intraperitoneally), Group II; DEX (0.4 mg/kg; intraperitoneally), Group III; selenium plus DEX (similar to Group II and Group IV), and Group IV; selenium (0.1 mg/kg; orally). At the end of the experiment, the rats' thymus, spleen, and lymph nodes were removed, processed, and stained by hematoxylin and eosin (H&E). The volume and volume density of theses organs were estimated by stereology. The results were analyzed using the Mann-Whitney U-test and the Kruskal-Wallis test. Results: The volume of the thymus as well as its cortex and medulla; the volume of the spleen as well as the volume density of its white pulp, periarterial lymphatic sheath zone, and follicles; and the volume of the lymph nodes as well as their inner (P=0.001) and outer (P=0.007) cortices showed a significant reduction in the DEX-treated animals in comparison with the controls. In the DEX plus selenium-treated animals, maximum effects were observed on the increment in the thymic cortex (P=0.001), the outer cortex of the lymph nodes (P=0.012), and the splenic follicles (P=0.018) in comparison with the DEX group. There was no significant difference between the animals receiving selenium treatment and the controls in terms of lymphoid organs. Conclusion: Selenium may improve lymphoid organ structures in an immunodeficiency rat model but has no effect on normal lymphoid tissues.

Effects of Ice Massage Prior to an Iontophoresis Treatment Using Dexamethasone Sodium Phosphate.

CONTEXT: Low current intensity iontophoresis treatments have increased skin perfusion over 700% from baseline potentially altering drug clearance from or diffusion to the targeted area. OBJECTIVE: To determine the effects of a preceding 10-minute ice massage on subcutaneous dexamethasone sodium phosphate (Dex-P) concentration and skin perfusion during and after a 4-mA iontophoresis treatment. DESIGN: Controlled laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four participants (male = 12, female = 12; age = 25.6 [4.5] y, height = 173.9 [8.51] cm, mass = 76.11 [16.84] kg). INTERVENTION(S): Participants were randomly assigned into 2 groups: (1) pretreatment 10-minute ice massage and (2) no pretreatment ice massage. Treatment consisted of an 80-mA·minute (4 mA, 20 min) Dex-P iontophoresis treatment. Microdialysis probes (3 mm deep in the forearm) were used to assess Dex-P, dexamethasone (Dex), and its metabolite (Dex-Met) concentrations. Skin perfusion was measured using laser Doppler flowmetry. MAIN OUTCOME MEASURE(S): Microdialysis samples were collected at baseline, at conclusion of treatment, and every 20 minutes posttreatment for 60 minutes. Samples were analyzed to determine Dex-Total (Dex-Total = Dex-P + Dex + Dex-Met). Skin perfusion was calculated as a percentage change from baseline. A mixed-design analysis of variance was used to determine Dex-Total and skin perfusion difference between groups overtime. RESULTS: There was no difference between groups (P = .476), but [Dex-Total] significantly increased over the course of the iontophoresis and posttreatment time (P < .001). Dex-P was measured in 18 of 24 participants with a mean concentration of 0.67 (1.09) µg/mL. Skin perfusion was significantly greater in the no ice treatment group (P = .002). Peak skin perfusion reached 27.74% (47.49%) and 117.39% (103.45%) from baseline for the ice and no ice groups, respectively. CONCLUSIONS: Ice massage prior to iontophoresis does not alter the tissue [Dex-Total] even with less skin perfusion.

Physiologically Based Pharmacokinetics of Dexamethasone in Rats.

Blood and multitissue concentration-time profiles for dexamethasone (DEX), a synthetic corticosteroid, were measured in male rats after subcutaneous bolus and infusion dosing. A physiologically based pharmacokinetics (PBPK) model was applied for 12 measured tissues. Tissue partition coefficients (K p ) and metabolic clearance were assessed from infusion studies. Blood cell to plasma partitioning (0.664) and plasma free fraction (0.175) for DEX were found to be moderate. DEX was extensively partitioned into liver (K p = 6.76), whereas the calculated K p values of most tissues ranged between 0.1 and 1.5. Despite the moderate lipophilicity of DEX (log P = 1.8), adipose exhibited very limited distribution (K p = 0.17). Presumably due to P-glycoprotein-mediated efflux, DEX concentrations were very low in brain compared with its expected high permeability. Infusion studies yielded K p values from male and female rats at steady state that were similar. In silico K p values calculated for different tissues by using GastroPlus software were similar to in vivo values except for adipose and liver. Glucocorticoid receptors are found in diverse tissues, and these PBPK modeling results may help provide exposure profiles driving pharmacodynamic effects of DEX. SIGNIFICANCE STATEMENT: Our physiologically based pharmacokinetics model describes the experimentally determined tissue and plasma dexamethasone (DEX) pharmacokinetics (PK) profiles in rats reasonably well. This model can serve for further investigation of DEX tissue distribution in rats as the PK driving force for PD effects in different tissues. No major sex differences were found for DEX tissue distribution. Knowledge gained in this study may be translatable to higher-order species including humans.

PLA-PCL-PEG-PCL-PLA based micelles for improving the ocular permeability of dexamethasone: development, characterization, and in vitro evaluation.

The aim of the present research was to investigate the feasibility of developing polylactide-polycaprolactone-polyethylene glycol-polycaprolactone-polylactide (PLA-PCL-PEG-PCL-PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA-PCL-PEG-PCL-PLA copolymers were synthesized by a ring-opening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an ex vivo bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull's distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA-PCL-PEG-PCL-PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.

Emergence of Ceftriaxone Resistance during a Case of Pneumococcal Meningitis with Fatal Evolution.

We report a case of a 62-year-old man treated for Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in the serum and cerebrospinal fluid (CSF). S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid 10 days after the isolation of the first strain. Isolate analysis showed that a mutation in the penicillin-binding protein 2X (PBP2X) has occurred under treatment.

A Lipid Micellar System Loaded with Dexamethasone Palmitate Alleviates Rheumatoid Arthritis.

Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo. To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund's Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.

Design and development of artemisinin and dexamethasone loaded topical nanodispersion for the effective treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) is a disease affecting the macula by the new blood vessels formation. AMD is widely treated with a combination of anti-angiogenic and anti-vascular endothelial growth factor (VEGF) agents. The topical administration of nanodispersions showed enhanced ocular residence time with controlled and prolonged drug delivery to the disease site at the back of the eye. In the present study we developed and characterized nanodispersion containing anti-angiogenic (artemisinin) and anti-VEGF agent (dexamethasone) for the topical ocular administration in order to obtain a required drug concentration in the posterior part of the eye. The nanodispersions were prepared with varying concentration of polymer, polyvinyl pyrrolidone K90 and polymeric surfactant, Poloxamer 407. The nanodispersions were found to be smooth and spherical in shape with a size range of 12-26 nm. In-vitro drug release studies showed the 90-101% of artemisinin and 55-103% of dexamethasone release from the nanodispersions. The blank formulation with a high concentration of polymer and polymeric surfactant showed an acceptable level of haemolysis and DNA damage. The chorioallantoic membrane assay suggested that the nanodispersion possess good anti-angiogenic effect. Hence the formulated artemisinin and dexamethasone nanodispersion may have the great potential for the AMD treatment.

Peptide-targeted liposomal delivery of dexamethasone for arthritis therapy.

Aim: Rheumatoid arthritis is an autoimmune disease affecting the joints. Antiarthritic drugs are given systemically, thereby exposing various healthy organs to these drugs, resulting in adverse reactions. Accordingly, there is an urgent need for targeted drug delivery methods for inflamed joints. Materials & methods: We developed a liposomal drug delivery system using a novel peptide ligand (CKPFDRALC) named ART-2, which homes to the inflamed joints when injected intravenously to rats with adjuvant-induced arthritis. Results: The ART-2-coated liposomes encapsulating an antiarthritic drug, dexamethasone (DEX), were more effective in inhibiting arthritis progression than control-DEX liposomes or free DEX, despite a comparable safety profile. Conclusion: Peptide-targeted therapy has advantages over conventional drug delivery and can be adapted for rheumatoid arthritis therapy.

Auraptene regulates Th1/Th2/TReg balances, NF-κB nuclear localization and nitric oxide production in normal and Th2 provoked situations in human isolated lymphocytes.

BACKGROUND: Auraptene as member of dietary coumarins, is found in citrus fruits. Former studies have demonstrated its anti-inflammatory and anti-cancer activity. PURPOSE: The mechanism of action and immune-modulatory property of this compound on human lymphocytes are greatly unknown. STUDY DESIGN/METHODS: The effect of three concentrations (10, 30 and 90 µM) of auraptene or dexamethasone (0.1 mM) were evaluated on percentage of cell proliferation and nitric oxide (NO) production as well as secretion and gene expression of cytokines, and NF-κB level in PHA-stimulated and non-stimulated lymphocytes. RESULTS: In non-stimulated cells, all three concentrations of auraptene significantly increased the gene expression index of IL-10 (P < 0.05-0.001). The IFN-γ gene expression index, IFN-γ/IL-4 and IL-10/IL-4 gene expression ratio were significantly increased due to the high concentration (90 µM) of auraptene treatment compared to control group (P < 0.05-0.001). In PHA stimulation, all three concentrations of the extract significantly decreased proliferation, cytokines (IL-4, IL-10 and IFN-γ) and NF-κB level as well as NO production, but IFN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased compared control group (P < 0.05-0.001). Gene expression of IL-10 and IL-4 was decreased but that of IFN-γ as well as FN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased due to all three concentrations of auraptene. CONCLUSION: The results showed promoting effects of auraptene on T cell subsets toward Th1 (IFN-γ) and Treg (IL-10), which suggest its therapeutic value for treatment of Th2 cells predominant diseases including allergic disease such as asthma and atopic dermatitis as well as cancers.

Efficacy of parthenolide on lung histopathology in a murine model of asthma

BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. Aim of the study: In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. RESULTS: Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. CONCLUSION: We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment

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Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends.

Dexamethasone is one of the most prescribed glucocorticoids. It is effective and safe in the treatment of a wide variety of ocular conditions, including anterior and posterior segment inflammation. However, its half-life in the vitreous humor is very short, which means that it typically requires frequent administrations, thus reducing patient adherence and causing therapeutic failure. Innovative dexamethasone delivery systems have been designed in an attempt to achieve sustained release and targeting. The FDA has approved dexamethasone implants for the treatment of macular edema secondary to retinal vein occlusion and posterior segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes, micelles and dendrimers are also proving to be adequate systems for maintaining optimal dexamethasone levels in the site of action. Pharmaceutical technology is turning a classical drug, dexamethasone, into a fashionable medicine.

High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.

PURPOSE: To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. METHODS: A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. RESULTS: No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). CONCLUSION: Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration of the drug as when the same dose is administered intramuscularly with demonstration of similar clinical effects.

Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study.

AIM: This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. METHODS: Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS: ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.

Pharmacokinetic evaluation of pomalidomide for the treatment of myeloma.

INTRODUCTION: Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within the relapse setting. Pomalidomide, a novel 4-amino derived from thalidomide, was recently introduced for the treatment of MM. In addition to being immune-adjuvant with anti-inflammatory properties, pomalidomide has shown several biological activities that directly and indirectly inhibit MM cells. AREAS COVERED: Herein, the authors review the chemistry, the mechanism of action and the pharmacokinetic properties of pomalidomide. The data reviewed within this article based on the relevant literature pertaining to pomalidomide's Phase I, II and III clinical trials. EXPERT OPINION: Pomalidomide has shown to be a safe and active agent, both alone and in combination with dexamethasone, in heavily pretreated patients. Furthermore, pomalidomide represents an effective treatment option for relapsed/refractory patients. Results from the ongoing trials evaluating the synergistic activity of pomalidomide combined with conventional chemotherapy or novel agents look promising and may prove to be viable treatment options in the future.

Intratympanic dexamethasone as initial therapy for idiopathic sudden sensorineural hearing loss: Clinical evaluation and laboratory investigation.

OBJECTIVE: To evaluate the effect of intratympanic dexamethasone (ITD) as initial therapy for idiopathic sudden sensorineural hearing loss (ISSHL) as well as to determine the concentration-dependent time course distribution of dexamethasone in the inner ear. METHODS: Sixty-six patients with profound ISSHL were included. Twenty-two were treated with ITD and the rest as control. Audiograms were performed before the treatment and one month afterwards. In the animal study, dexamethasone of different concentrations (5, 10 and 20mg/ml) was injected into the tympanums of three groups of SD rats (Groups A, B and C), their inner ears dissected free at various postinjection survival intervals. Immunofluorescence was applied to detect the locations of dexamethasone. RESULTS: The overall rate of good prognosis was 77.27% in ITD group, which was not significantly different from 81.82% in the control group. In the animal study, the higher local concentration and longer lasting period was found in Groups B and C. CONCLUSIONS: ITD at 5mg/ml did not add effect to systemic steroids in improving hearing outcomes in patients with ISSHL. An increase in dexamethasone concentration led to large variations in pharmacokinetics in animal study, showing potential value in optimizing the drug delivery protocols and improving the therapeutic results.

Development and validation of a fast and sensitive bioanalytical method for the quantitative determination of glucocorticoids--quantitative measurement of dexamethasone in rabbit ocular matrices by liquid chromatography tandem mass spectrometry.

A sensitive, selective, accurate and robust LC-MS/MS method was developed and validated for the quantitative determination of glucocorticoids in rabbit ocular tissues. Samples were processed by a simple liquid-liquid extraction procedure. Chromatographic separation was performed on Phenomenex reversed phase C18 gemini column (50mmx4.6mm i.d.,) with an isocratic mobile phase composed of 30% of acetonitrile in water containing 0.1% of formic acid, at a flow rate 0.2mL/min. Dexamethasone (DEX), prednisolone (PD) and hydrocortisone (HD) were detected with proton adducts at m/z 393.20-->355.30, 361.30-->147.20 and 363.20-->121.0 in multiple reaction monitoring (MRM) positive mode respectively. Finally, 50microL of 0.1% novel DEX mixed micellar formulation was topically administered to a rabbit eye and concentrations were measured. The method was validated over a linear concentration range of 2.7-617.6ng/mL. Lower limit of quantitation (LLOQ) of DEX and PD was measured in the concentration range of 2.7 and 11.0ng/mL respectively. The resulting method demonstrated intra and inter-day precision within 13.3% and 11.1% and accuracy within 19.3% and 12.5% for DEX and PD, respectively. Both analytes were found to be stable throughout freeze-thaw cycles and during bench top and postoperative stability studies (r(2)>0.999). DEX concentrations in various ocular tissue samples i.e., aqueous humor, cornea, iris ciliary body, sclera and retina choroid were found to be 344.0, 1050.07, 529.6, 103.9 and 48.5ng/mg protein respectively. Absorption of DEX after topical administration from a novel aqueous mixed micellar formulation achieved therapeutic concentration levels in posterior segment of the rabbit eye.

Magnetically retainable microparticles for drug delivery to the joint: efficacy studies in an antigen-induced arthritis model in mice.

INTRODUCTION: Conventional corticosteroid suspensions for the intra-articular treatment of arthritis suffer from limitations such as crystal formation or rapid clearance from the joint. The purpose of this study was to investigate an innovative alternative consisting of corticosteroid encapsulation into magnetically retainable microparticles. METHODS: Microparticles (1 or 10 microm) containing both superparamagnetic iron oxide nanoparticles (SPIONs) and dexamethasone 21-acetate (DXM) were prepared. In a preliminary study, we compared the persistence of microparticles of both sizes in the joint. A second study evaluated the influence of a subcutaneously implanted magnet near the knee on the retention of magnetic microparticles in the joint by in vivo imaging. Finally, the efficacy of 10-microm microparticles was investigated using a model of antigen-induced arthritis (AIA) in mice. Phosphate-buffered saline, DXM suspension, SPION suspension, blank microparticles and microparticles containing only SPIONs were used as controls. Arthritis severity was assessed using 99mTc accumulation and histological scoring. RESULTS: Due to their capacity of encapsulating more corticosteroid and their increased joint retention, the 10-microm microparticles were more suitable vectors than the 1-microm microparticles for corticosteroid delivery to the joint. The presence of a magnet resulted in higher magnetic retention in the joint, as demonstrated by a higher fluorescence signal. The therapeutic efficacy in AIA of 10-microm microparticles containing DXM and SPIONs was similar to that of the DXM suspension, proving that the bioactive agent is released. Moreover, the anti-inflammatory effect of DXM-containing microparticles was more important than that of blank microparticles or microparticles containing only SPIONs. The presence of a magnet did not induce a greater inflammatory reaction. CONCLUSIONS: This study confirms the effectiveness of an innovative approach of using magnetically retainable microparticles as intra-articular drug delivery systems. A major advantage comes from a versatile polymer matrix, which allows the encapsulation of many classes of therapeutic agents (for example, p38 mitogen-activated protein kinase inhibitors), which may reduce systemic side effects.

Anti-eosinophilic effect of Lafoensia pacari in toxocariasis.

We previously reported the anti-inflammatory activity of Lafoensia pacari extract in Toxocara canis infection, a model of systemic IL-5-dependent eosinophil migration. In the present study, we describe the kinetics of the anti-inflammatory activity of L. pacari extract and compare it with dexamethasone. T. canis-infected mice were submitted to different treatment protocols and the cells present in bronchoalveolar space and peritoneal cavity were collected at the end of each treatment period. The results showed that L. pacari extract effectively inhibited eosinophil migration only when the treatment was initiated before the peak of eosinophil migration (1st to 18th; 12th to 18th and 12th to 24th day post-infection). When eosinophil migration was established, administration of L. pacari extract had no effect on it (treatment 18th to 24th day post-infection). Dexamethasone was effective in inhibiting eosinophil migration in all periods studied. We suggest that L. pacari extract can potentially be a natural alternative treatment of eosinophilic diseases.

En niños con laringitis aguda una dosis de dexametasona oral es más eficaz que una de prednisolona / In children with croup one oral dexamethasone doses is more effective than one of prednisolone

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[Preliminary study on brain-targeted drug delivery via inner ear].

The article investigates the feasibility of delivering drugs to brain via inner ear, and provides a novel route for delivering drugs to the brain tissues. Dexamethasone acetate (DA)-loaded solid lipid nanoparticles (SLN) was prepared by using Compritol 888 ATO as material. HPLC assays for the determination of DA, dexamethasone sodium phosphate (DSP) and dexamethasone (Dex) were developed, separately. DA-loaded SLN and DSP solution were administered after intratympanic injection (IT) or intravenous injection (IV). Perilymph ( PL) and cerebrospinal fluid (CSF) were collected periodically. The concentrations in PL and CSF were measured by HPLC, and used to estimate pharmacokinetic parameters of Dex in CSF. The AUC of Dex in CSF following IT DA-loaded SLN or DSP solution were respectively 2.5 and 4.3-fold higher than those following IV. After IT, DA-loaded SLN increased the AUC by 13 times and extended the MRT by 19 times, compared with the solution. Moreover, the AUC of Dex in PL following IT the SLN was 76% lower than that following IT the solution. Intra-cochlear administration shows great potential and offers a promising alternative to brain-targeted drug delivery.