Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability.

BACKGROUND AND PURPOSE: The traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability. METHODS: The crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated. RESULTS: Soluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months. CONCLUSION: These results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.

Preparation and antitumor evaluation of hinokiflavone hybrid micelles with mitochondria targeted for lung adenocarcinoma treatment.

Hinokiflavone (HF) is a natural biflavonoid extracted from medicinal plants such as Selaginella tamariscina and Platycladus orientalis. HF plays a crucial role in the treatment of several cancers. However, its poor solubility, instability, and low bioavailability have limited its use. In this study, soluplus/d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS)/dequalinium (DQA) was applied to improve the solubilization efficiency and stability of HF. HF hybrid micelles were prepared via thin-film hydration method. The physicochemical properties of micelles, including particle size, zeta potential, encapsulation efficiency, drug loading, CMC value, and stability were investigated. The in vitro cytotoxicity assay showed that the cytotoxicity of the HF hybrid micelles was higher than that of free HF. In addition, the HF hybrid micelles improved anticancer efficacy and induced mitochondria-mediated apoptosis, which is associated with the high levels of ROS inducing decreased mitochondrial membrane potential, promoting apoptosis of tumor cells. Furthermore, in vivo tumor suppression, smaller tumor volume and increased expression of pro-apoptotic proteins were found in nude mice treated with HF hybrid micelles, suggesting that HF hybrid micelles had stronger tumor suppressive activity compared with free HF. In summary, HF hybrid micelles developed in this study enhanced antitumor effect, which may be a potential drug delivery system for the treatment of lung adenocarcinoma.

Future liver remnant growth after various portal vein embolization regimens: a quantitative comparison.

Purpose: To compare the efficacy of right portal vein embolization using ethylene vinyl alcohol (EVOH-PVE) compared to other embolic agents and surgical right portal vein ligation (PVL).Material and methods: Patients with right sided liver malignancies scheduled for extensive surgery and receiving induction of liver hypertrophy via right portal vein embolization/ligature between 2010-2016 were retrospectively evaluated. Treatments included were ethylene vinyl alcohol copolymer (Onyx®, EVOH-PVE), ethiodized oil (Lipiodol®, Lipiodol/PVA-PVE), polyvinyl alcohol (PVA-PVE) or surgical ligature (PVL). Liver segments S2/3 were used to assess hypertrophy. Primary outcome was future liver remnant growth in ml/day.Results: Forty-one patients were included (EVOH-PVE n = 11; Lipiodol/PVA-PVE n = 10; PVA-PVE n = 8; PVL n = 12), the majority presenting with cholangiocarcinoma and colorectal metastases (n = 11; n = 27). Pre-interventional liver volumes were comparable (p = .095). Liver hypertrophy was successfully induced in all but one patient receiving Lipiodol/PVA-PVE. Liver segment S2/3 growth was largest for EVOH-PVE (5.38 ml/d) followed by PVA-PVE (2.5 ml/d), with significantly higher growth rates than PVL (1.24 ml/d; p < .001; p = .007). No significant difference was evident for Lipiodol/PVA-PVE (1.43 ml/d, p = .809).Conclusions: Portal vein embolization using EVOH demonstrates fastest S2/3 growth rates compared to other embolic agents and PVL, potentially due to its permanent portal vein embolization and induction of hepatic inflammation.

Evaluation of a novel liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in an animal endovascular embolization model.

BACKGROUND: The choice of the embolic agent and the embolization technique can have a significant impact on the success of endovascular embolization. OBJECTIVE: To evaluate a novel iodinated copolymer-based liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in the porcine rete mirabile (RM), serving as an endovascular embolization model. Onyx, as an established liquid embolic agent, served as comparator. MATERIALS AND METHODS: Sixteen embolization procedures were performed using PHIL (n=8) or Onyx (n=8) as liquid embolic agent. Waiting time between injections was set to 30 or 60 s (n=4 per study group). Survival time after intervention was 2 hours or 7 days. Embolization characteristics (eg, procedure times, number of injections and volume of embolic agent) and embolization extent (percentage of embolized RM in post-interventional x-ray) were assessed. Post-interventional CT and histopathological analyses were performed. RESULTS: Embolization characteristics and embolization extent were not significantly different for PHIL and Onyx, including subgroups (eg, embolization extent 44% vs 69% (medians); p=0.101). For PHIL, extension of the waiting time from 30 to 60 s led to a significantly higher embolization extent (24% vs 72% (medians); p=0.035). Moderate disintegration and mild inflammation of the embolized blood vessels were present for both embolic agents. CONCLUSION: PHIL is feasible for transarterial embolization in an acute and subacute endovascular embolization model. In this preliminary experimental in vivo study, embolization characteristics, embolization extent, and biocompatibility seem to be similar to those of Onyx.

Antitumour efficacy of Piper tuberculatum and piplartine based on the hollow fiber assay.

Piper tuberculatum, popularly known in Brazil as "jaborandi falso" and "pimenta darta", is widely used in folk medicine for the treatment of several diseases. In this study, the in vivo hollow fiber assay was used to investigate the antitumour efficacy of the crude extract and piplartine obtained from P. tuberculatum roots. Human glioblastoma (SF-295) and colon carcinoma (HCT-8) cell lines were used. In vitro cytotoxicity was assayed by the MTT assay. In the hollow fiber assay, nude mice implanted with tumour cells in hollow fibers were treated for four consecutive days via the intraperitoneal route, and tumour cell populations were assessed by the MTT assay. Both the crude extract and piplartine displayed cytotoxicity. In the hollow fiber assay, tumour growth inhibition rates were 24.6-54.8 % for the crude extract and 33.7-62.2 % for piplartine. No signal of toxicity was noticed. In conclusion, the crude extract and piplartine obtained from P. tuberculatum roots displayed in vitro and in vivo anticancer efficacy.

Onyx embolization of an avulsed thalamoperforator following endoscopic colloid cyst and lamina terminalis fenestration.

A patient presented with headaches and was found to have a colloid cyst in the third ventricle and ventriculomegaly. The patient underwent endoscopic colloid cyst resection and third ventriculostomy without incidence. Prior to emergence, a blown right pupil was acutely noted, and bright red blood emanated from the ventricular drain that was routinely placed in the endoscopy tract at the conclusion of the procedure. CTangiography demonstrated active extravasation from the pre-pontine cistern into the third ventricle and subarachnoid space. Emergency DSA confirmed active extravasation from an avulsed thalamoperforator arising from the proximal right P1 posterior cerebral artery, which was immediately embolized without incident.

Development and evaluation of chitosan and chitosan/Kollicoat® Smartseal 30 D film-coated tablets for colon targeting.

The aim of the present study was to develop film-coated tablets which release a minor amount of the active pharmaceutical ingredient (API) into the stomach and small intestine, yet show a sharp increase of drug release in the colon. Tablets containing the model drug Diclofenac-Na, microcrystalline cellulose as a filler (MT), as well as tablets consisting of Ludiflash® (LT), both were used as tablet cores, respectively. Either chitosan (CHI) alone or different ratios of chitosan and Kollicoat® Smartseal 30 D (KCSS) were applied onto these cores. The resulting film-coated tablets were analyzed for swelling, drug dissolution and stability. In order to clarify whether the colon release is mainly enzyme-driven or pressure-controlled, the coated tablets were both tested in the colon microflora test (CMT), which simulates the enzyme environment within the colon, and using a bio-relevant dissolution apparatus mimicking the intraluminal pressures and stress conditions present in the gastrointestinal tract (GIT). CHI/KCSS (25:75) coated LTs showed a pressure-controlled site-specific drug release in the large intestine, while remaining intact in the upper GIT. CHI as well as CHI/KCSS (25:75) applied onto MTs, remained stable during the entire simulated bio-relevant dissolution transit of the GIT, but showed enzymatically controlled colon targeting in the CMT. These results could be confirmed for CHI/KCSS (25:75) film-coated MTs top-coated with an additional hydroxypropylmethylcellulose (HPMC) layer and an Eudragit L 30 D-55 (EUL) layer to avoid the dissolution in the fasting stomach.

Forcible intraarterial injection of a nonadhesive liquid embolic agent under microballoon occlusion: experimental study in swine liver.

PURPOSE: To evaluate the feasibility and effectiveness of transcatheter embolization by forcible intraarterial injection of a mixture of ethylene vinyl alcohol copolymer (EVAL) and ethanol under microballoon occlusion compared with conventional transcatheter arterial embolization methods in nontumoral swine liver. MATERIALS AND METHODS: Nine swine were divided into three groups: embolization with EVAL/ethanol mixture (EVAL group, n = 5), with ethiodized oil (ethiodized oil group, n = 2), and with microspheres (microspheres group, n = 2). Embolization was performed at the subsegmental hepatic artery. The EVAL/ethanol mixture was injected forcibly through a microcatheter with a balloon, which was inflated to prevent backflow of the mixture during the injection. Ethiodized oil or microspheres were injected into the artery using a microcatheter without balloon occlusion. Two animals of the EVAL group were euthanized immediately after embolization, and the distribution of EVAL was assessed microscopically. The remaining seven animals were euthanized 4 weeks after embolization, and the histopathologic changes were assessed. RESULTS: All procedures were technically successful. EVAL occupied > 80% of the hepatic arterial, portal venous, and sinusoidal lumens after embolization. Ischemic coagulation necrosis was observed 4 weeks after embolization in the EVAL group. Parenchymal necrosis was not observed in the ethiodized oil and microspheres groups. CONCLUSIONS: Transcatheter embolization by forcible intraarterial injection of an EVAL/ethanol mixture under microballoon occlusion was feasible and achieved the simultaneous embolization of hepatic artery, portal vein, and sinusoids in swine liver, resulting in complete necrosis of the segment that received embolization.

Functional textiles for atopic dermatitis: a systematic review and meta-analysis.

Atopic dermatitis (AD) is a relapsing inflammatory skin disease with a considerable social and economic burden. Functional textiles may have antimicrobial and antipruritic properties and have been used as complementary treatment in AD. We aimed to assess their effectiveness and safety in this setting. We carried out a systematic review of three large biomedical databases. GRADE approach was used to rate the levels of evidence and grade of recommendation. Meta-analyses of comparable studies were carried out. Thirteen studies (eight randomized controlled trials and five observational studies) met the eligibility criteria. Interventions were limited to silk (six studies), silver-coated cotton (five studies), borage oil, and ethylene vinyl alcohol (EVOH) fiber (one study each). Silver textiles were associated with improvement in SCORAD (2 of 4), fewer symptoms, a lower need for rescue medication (1 of 2), no difference in quality of life, decreased Staphyloccosus aureus colonization (2 of 3), and improvement of trans-epidermal water loss (1 of 2), with no safety concerns. Silk textile use was associated with improvement in SCORAD and symptoms (2 of 4), with no differences in quality of life or need for rescue medication. With borage oil use only skin erythema showed improvement, and with EVOH fiber, an improvement in eczema severity was reported. Recommendation for the use of functional textiles in AD treatment is weak, supported by low quality of evidence regarding effectiveness in AD symptoms and severity, with no evidence of hazardous consequences with their use. More studies with better methodology and longer follow-up are needed.

Bulking agents: an analysis of 500 cases and review of the literature.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is common, impacts women's quality of life, and generates high costs. Physiotherapy is the first-line therapy, and if it fails, suburethral slings are the gold standard in SUI surgery. Bulking agents injected periurethrally might be a beneficial alternative, but there is a paucity of data on bulking therapy. The aim of this study was to prospectively analyze the efficacy and safety of bulking agents in the setting of a tertiary referral center. METHODS: In the last 13 years, 514 elderly women with SUI were treated by injection therapy with either collagen (Contigen), hyaluronic acid (Zuidex), ethylene vinyl alcohol (Tegress), or polyacrylamide hydrogel (Bulkamid). Subjective and objective outcome was recorded at the 12-month postoperative appointment using the King's Health Questionnaire, visual analogue scale (VAS) describing their incontinence severity, standardized pad test, and urethral pressure profile. RESULTS: Demographic data were equally distributed in all four groups of agents used. Sixty-one patients were lost to follow-up (10.6 %). Statistically significant changes were found for maximum urethral closure pressure (MUCP), pad weight, and VAS before and after bulking for the four agents used. Pad test was negative in 73.2 % of patients after bulking therapy. Subjective assessment showed improvements in general health and role limitations. The overall complication rate was low for all agents. CONCLUSIONS: This study shows improvement in incontinence after bulking therapy according to subjective and objective outcomes in an elderly population. In contrast to earlier reports, side effects due to injections were few and mild. We can advocate bulking therapy for treating SUI, as it is simple, safe, and shows both objective and subjective improvement and relief.

Formulation study and evaluation of matrix and three-layer tablet sustained drug delivery systems based on Carbopols with isosorbite mononitrate.

The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core containing the drug. The findings of the study indicated that all systems demonstrated sustained release. The properties of the polymer used and the structure of each formulation appear to considerably affect drug release and its release rate. The three-layer formulations exhibit lower drug release compared to the matrices. This was due to the fact that the barrier-layers hindered the penetration of liquid into the core and modified drug dissolution and release. The geometrical characteristics/structure of the tablets as well as the weight/thickness of the barriers-layers considerably influence the rate of drug release and the release mechanisms. Kinetic analysis of the data indicated that drug release from matrices was mainly attributed to Fickian diffusion while three-layer tablets exhibited either anomalous diffusion or erosion/relaxation mechanisms. The advantage of Carbopol formulations is that a range of release profiles can easily be obtained through variations in tablet structure and thus Carbopols are appropriate carriers of oral sustained drug delivery systems for soluble drugs such as the isosorbite mononitrate.

Rheological evaluation of silicon/carbopol hydrophilic gel systems as a vehicle for delivery of water insoluble drugs.

The present study analyzed the thickening properties of Carbopol 974 and 971 in a 50:50 mixture of water/Silsense A-21, a new cationic silicon miscible in any proportion with water. Samples were prepared by simply dispersing different Carbopol amounts (0.5-4%) at room temperature or at 70 degrees C without neutralizing. Temperature sweep and time sweep analysis did not reveal significant structural changes at increasing temperature in the samples prepared following the first procedure. On the other hand systems obtained at 70 degrees C possessed higher elastic character particularly at polymer concentration higher than 2% (w/v). Analysis of the G' and G'' vs frequency curves by using different fitting equations (linear fitting, power law) gave information about the viscoelastic properties of the systems. The fitting of the frequency spectra and the calculation of the relaxation times from the master curves outlined the structural differences within the samples prepared with the two different procedures, confirming stronger gel-like behaviour for the samples prepared by the heating procedure. High preparation temperature promoted the polymer-solvent interactions, aiding the solvation of Carbopol. Heating facilitated polymer-solvent and polymer-polymer interaction, giving rise to a better organised structure typical of gel-like systems. Furthermore this preparation method provided good stability properties as shown by the stress sweeps tests performed during the three months of storage. The interpretation of the rheological results was supported by statistical analysis. A design methodology (screening and optimisation) was also applied in order evaluate the influence on dynamic rheological moduli of several parameters (polymer type and concentration, preparation method, temperature of the tests). This last method showed the relevance of the interaction of two main factors: polymer concentration and preparation procedure. Thus, statistical analysis confirmed that temperature increased the polymer-solvent interaction and improved the viscoelastic properties of the systems, particularly when Carbopols were present in considerable amounts.

Comparison of preparation design and material thickness on microbial leakage through Cavit using a tooth model system.

Few studies have compared Cavit thickness and access design as factors in microbial leakage. The present study used an acrylic tooth model to measure leakage of Streptococcus mutans. Pilot studies confirming the sterility of Cavit showed it will inhibit microbial growth for 2 days. The experiments compared class I preparations where Cavit thickness was 4 mm with class II preparations where thickness was 2-3 mm. Accesses sealed with cotton pellets were compared with those without cotton. Results of the study showed no bacterial contamination in any of the class I samples (up to 14 days). Some class II samples showed contamination at day 1 (3 out of 14), with all contaminated at day 7 (14 of 14), yet only 1 contaminated at day 14 (1 out of 14). The results suggest that a 4-mm thickness of Cavit should prevent bacterial ingress for at least 2 weeks, but microbial leakage may occur if temporary thickness is less than 3 mm or in a complex access preparation.

Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver.

PURPOSE: To assess the toxicity and efficacy of chemoembolization and bland embolization in patients with neuroendocrine tumor metastases to the liver. MATERIALS AND METHODS: A total of 67 patients underwent 219 embolization procedures: 23 patients received primarily bland embolization with PVA with or without iodized oil and 44 primarily received chemoembolization with cisplatin, doxorubicin, mitomycin-C, iodized oil, and polyvinyl alcohol. Clinical, laboratory, and imaging follow-up was performed 1 month after completion of therapy and every 3 months thereafter. Patients with disease relapse were treated again when feasible. Toxicity was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. Efficacy was assessed by clinical and morphologic response. Time to progression (TTP), time to treatment failure, and survival were estimated by Kaplan-Meier analysis. RESULTS: Ten of 67 patients (15%) were lost to follow-up. The mortality rate at 30 days was 1.4%. Toxicities of grade 3 or worse in severity occurred after 25% of chemoembolization procedures and 22% of bland embolization procedures (odds ratio, 1.2; 95% CI, 0.4-4.0). Mean length of stay was 1.5 day in both groups. Rates of freedom from progression at 1, 2, and 3 years were 49%, 49%, and 35% after chemoembolization and 0%, 0%, and 0% after bland embolization (log-rank test, P = .16). Among the subgroup with carcinoid tumors, the proportions without progression were 65%, 65%, and 52% after chemoembolization and 0%, 0%, and 0% after bland embolization (log-rank test, P = .08). Patients treated with chemoembolization and bland embolization experienced symptomatic relief for means of 15 and 7.5 months, respectively (P = .14). Survival rates at 1, 3, and 5 years after therapy were 86%, 67%, and 50%, respectively, after chemoembolization and 68%, 46%, and 33%, respectively, after bland embolization (log-rank test, P = .18). CONCLUSIONS: Chemoembolization was not associated with a higher degree of toxicity than bland embolization. Chemoembolization demonstrated trends toward improvement in TTP, symptom control, and survival. Based on these results, a multicenter prospective randomized trial is warranted.

Biofilm reduction by a new burn gel that targets nociception.

AIMS: To compare the ability of an amorphous first aid topical gel containing vinegar, citric acid and EDTA (RescuDerm(TM); RESC) and various derivative formulations to eradicate Pseudomonas aeruginosa (PSEUD) and Staphylococcus epidermidis (STAPH) biofilms. METHODS AND RESULTS: 24-h biofilms prepared using the Minimum Biofilm Elimination Concentration (MBEC) Assay System were exposed for 4 or 24 h to the different gel formulations. Citric acid-free, acetic acid-free or acetic acid-free/sodium acetate-supplemented RESC gels reduced PSEUD and STAPH biofilm formation as effectively as RESC. Substituting the weak organic acids with equivalent concentrations of glacial acetic acid reduced the effectiveness of gel against PSEUD and STAPH biofilms by half, but viable bacterial counts still remained below 4 log(10) CFU/peg. Removal of gelling agent and/or EDTA enhanced efficacy against PSEUD but not STAPH biofilms. An acidified placebo gel formulation generated an only marginal bactericidal effect compared to that of RESC. CONCLUSIONS: RESC is a promising new antimicrobial agent. Its weak organic acid content, rather than merely acidic pH, mediates its considerable in vitro bactericidal efficacy against bacterial biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: These data, taken together with the observation that RescuDerm possesses broad in vitro bactericidal activity against other pathogen species, suggest the potential usefulness of this product for controlling biofilm formation on a variety of cutaneous traumatic and surgical wounds.

Effect of thickener agents on dental enamel microhardness submitted to at-home bleaching.

Dental bleaching occurs due to an oxidation reaction between the bleaching agents and the macromolecules of pigments in the teeth. This reaction is unspecific and the peroxides can also affect the dental matrix causing mineral loss. On the other hand, recent studies have suggested that the thickener agent carbopol can also cause mineral loss. Thus, the objective of this study was to evaluate in vitro the effect of at-home dental bleaching on dental enamel microhardness after the use of bleaching agents with and without carbopol as a thickener agent. Bovine dental slabs with 3 x 3 x 3 mm were obtained, sequentially polished, and randomly divided into 4 groups according to the experimental treatment: G1: 2% carbopol; G2: 10% carbamide peroxide with carbopol; G3: carbowax; G4: 10% carbamide peroxide with poloxamer. Bleaching was performed daily for 4 weeks, immersed in artificial saliva. Enamel microhardness values were obtained before the treatment (T0) and 7 (T1), 14 (T2), 21 (T3), 28 (T4), and 42 (T5) days after the beginning of the treatment. ANOVA and Tukey's test revealed statistically significant differences only for the factor Time (F = 5.48; p < 0.01). All bleaching and thickener agents caused no alterations on the enamel microhardness.

Effect of thickener agents on dental enamel microhardness submitted to at-home bleaching

Dental bleaching occurs due to an oxidation reaction between the bleaching agents and the macromolecules of pigments in the teeth. This reaction is unspecific and the peroxides can also affect the dental matrix causing mineral loss. On the other hand, recent studies have suggested that the thickener agent carbopol can also cause mineral loss. Thus, the objective of this study was to evaluate in vitro the effect of at-home dental bleaching on dental enamel microhardness after the use of bleaching agents with and without carbopol as a thickener agent. Bovine dental slabs with 3 x 3 x 3 mm were obtained, sequentially polished, and randomly divided into 4 groups according to the experimental treatment: G1: 2 percent carbopol; G2: 10 percent carbamide peroxide with carbopol; G3: carbowax; G4: 10 percent carbamide peroxide with poloxamer. Bleaching was performed daily for 4 weeks, immersed in artificial saliva. Enamel microhardness values were obtained before the treatment (T0) and 7 (T1), 14 (T2), 21 (T3), 28 (T4), and 42 (T5) days after the beginning of the treatment. ANOVA and Tukey's test revealed statistically significant differences only for the factor Time (F = 5.48; p < 0.01). All bleaching and thickener agents caused no alterations on the enamel microhardness.

O clareamento dental ocorre devido a uma reação de oxidação entre o agente clareador e as macromoléculas de pigmentos presentes nos dentes. Esta reação é inespecífica e o peróxido pode agir na matriz dental causando perdas de mineral. Por outro lado, estudos recentes sugerem que o agente espessante carbopol também pode causar perda mineral. Assim, o objetivo deste trabalho foi avaliar in vitro o efeito do clareamento caseiro sobre a microdureza do esmalte após o uso de agentes clareadores com e sem carbopol como espessante. Fragmentos de esmalte bovino de 3 x 3 x 3 mm foram obtidos, polidos seqüencialmente e aleatoriamente divididos em 4 grupos de acordo com o tratamento experimental: G1: carbopol a 2 por cento; G2: peróxido de carbamida a 10 por cento com carbopol; G3: carbowax; G4: peróxido de carbamida a 10 por cento com poloxamer. O clareamento foi realizado diariamente por 4 semanas em saliva artificial. A microdureza do esmalte foi avaliada antes (T0) e após 7 (T1), 14 (T2), 21 (T3), 28 (T4), e 42 (T5) dias do início do tratamento. A ANOVA e o teste de Tukey revelaram diferenças estatísticas significantes somente para o fator Tempo (F = 5,48; p < 0,01). Os agentes clareadores e espessantes não causaram alterações na microdureza do esmalte.

Enteryx implantation for GERD: expanded multicenter trial results and interim postapproval follow-up to 24 months.

BACKGROUND: Enteryx implantation in the esophagus is an alternative therapy for patients with proton pump inhibitor (PPI) dependent GERD. Although this treatment resulted in highly significant improvement at 6 and 12 months, longer follow-up is needed to more fully assess the durability of these positive effects. METHODS: An open-label, international clinical trial was conducted in 144 PPI-dependent patients with GERD with follow-up at 6 and 12 months. In addition, the durability and the safety of the treatment were assessed for 24 months in 64 patients enrolled in a postapproval study. The primary study outcome measure was usage of PPI. Secondary outcomes in the multicenter trial were GERD health-related quality of life (GERD-HRQL) symptom score and esophageal acid exposure. RESULTS: At 12 months, PPI use was reduced > or =50% in 84%: 95% confidence interval (CI) [76%, 90%] and was eliminated in 73%: 95% CI[64%, 81%] of evaluable patients (intent-to-treat analysis 78%: 95% CI[70%, 84%] and 68%: 95% CI[60%, 76%], respectively). A GERD-HRQL < or =11 was attained in 78%: 95% CI[69%, 85%] of evaluable patients. Esophageal acid exposure (total time pH <4) was reduced by 31%: 95% CI[17%, 43%]. At 24 months, a > or =50% or greater reduction in PPI use was achieved in 72%: 95% CI[59%, 82%] and PPI use was eliminated in 67%: 95% CI[54%, 78%] of patients. CONCLUSIONS: This investigation provides evidence for sustained effectiveness and safety of implantation of Enteryx in the esophagus in PPI-dependent patients with GERD.

[Endoscopic treatment of gastroesophageal reflux disease]. / Tratamiento endoscópico de la enfermedad por reflujo gastroesofágico.

"Gastroesophageal reflux disease is a chronic illness with a wide spectrum of symptoms that can significantly affect people's quality of life and increase the risk of complications, including cancer. Gastroesophageal reflux disease has been primarily treated with anti-secretory medications and, when needed, surgery. However, caveats to this approach include long-term medications, side effects, drug-interaction, cost, and the morbidity and mortality associated with surgery. Endoscopic management of gastroesophageal reflux disease offers a safe, effective and less invasive alternative to medications and surgery. There are different endoscopic therapies that include suturing, application of radiofrequency, injection of polymer, and placement of prostheses. The available data on these therapies is here discussed".

An investigation of the role of auditory cortex in sound localization using muscimol-releasing Elvax.

Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABA(A) receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I-IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to < or = 500 microm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol-Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.