Liposomal Lidocaine Gel For Topical Use At The Oral Mucosa: Characterization, In Vitro Assays And In Vivo Anesthetic Efficacy In Humans.

To characterize liposomal-lidocaine formulations for topical use on oral mucosa and to compare their in vitro permeation and in vivo anesthetic efficacy with commercially available lidocaine formulations. Large unilamellar liposomes (400 nm) containing lidocaine were prepared using phosphatidylcholine, cholesterol, and α-tocoferol (4:3:0.07, w:w:w) and were characterized in terms of membrane/water partition coefficient, encapsulation efficiency, size, polydispersity, zeta potential, and in vitro release. In vitro permeation across pig palatal mucosa and in vivo topical anesthetic efficacy on the palatal mucosa in healthy volunteers (double-blinded cross-over, placebo controlled study) were performed. The following formulations were tested: liposome-encapsulated 5% lidocaine (Liposome-Lido5); liposome-encapsulated 2.5% lidocaine (Liposome-Lido2.5); 5% lidocaine ointment (Xylocaina®), and eutectic mixture of lidocaine and prilocaine 2.5% (EMLA®). The Liposome-Lido5 and EMLA showed the best in vitro permeation parameters (flux and permeability coefficient) in comparison with Xylocaina and placebo groups, as well as the best in vivo topical anesthetic efficacy. We successfully developed and characterized a liposome encapsulated 5% lidocaine gel. It could be considered an option to other topical anesthetic agents for oral mucosa.

Effect Of Atorvastatin On Wound Healing In Rats.

Skin-wound healing is a complex and dynamic biological process involving inflammation, proliferation, and remodeling. Recent studies have shown that statins are new therapeutical options because of their actions, such as anti-inflammatory and antioxidant activity, on vasodilation, endothelial dysfunction and neoangiogenesis, which are independent of their lipid-lowering action. Our aim was to investigate the effect of atorvastatin on tissue repair after acute injury in healthy animals. Rats were divided into four groups: placebo-treated (P), topical atorvastatin-treated (AT), oral atorvastatin-treated (AO), topical and oral atorvastatin-treated (ATO). Under anesthesia, rats were wounded with an 8-mm punch in the dorsal region. Lesions were photographed on Days 0, 1, 3, 7, 10, 12, and 14 post-injury and samples taken on Days 1, 3, 7, and 14 for protein-expression analysis of insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase (GSK)-3, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK), interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Upon macroscopic examination, we observed significant reductions of lesion areas in groups AT, AO, and ATO compared to the P group. Additionally, AT and AO groups showed increased expression of IRS-1, PI3K, Akt, GSK-3, and IL-10 on Days 1 and 3 when compared with the P group. All atorvastatin-treated groups showed higher expression of IRS-1, PI3K, Akt, GSK-3, IL-10, eNOS, VEGF, and ERK on Day 7. On Days 1, 3, and 7, all atorvastatin-treated groups showed lower expression of IL-6 and TNF-α when compared with the P group. We conclude that atorvastatin accelerated tissue repair of acute lesions in rats and modulated expressions of proteins and cytokines associated with cell-growth pathways.

Pharmacokinetic And Pharmacodynamic Evaluation Of A Nanotechnological Topical Formulation Of Lidocaine/prilocaine (nanorap) In Healthy Volunteers.

Nanorap is a new nanotechnological formulation for topical anesthesia composed of lidocaine (2.5%) and prilocaine (2.5%). The present study evaluated the pharmacokinetics (PK) of Nanorap. For the determination of lidocaine and prilocaine in human plasma a new method using high-performance liquid-chromatography coupled to tandem mass spectrometry was developed. Nanorap pharmacodynamic (PD) and its physical proprieties were also evaluated. Nanorap was administered by topical application of 2g to healthy volunteers and blood samples were collected for the PK analysis. The drugs were extracted from plasma by liquid-liquid extraction with ether/hexane (80/20, v/v). The chromatography separation was performed on a Genesis C18 analytical column 4 µm (100 x 2.1 mm i.d.) with a mobile phase of methanol/acetonitrile/water (40/30/30, for lidocaine, and 50/30/20, for prilocaine, v/v/v) + 2 mM of ammonium acetate and ropivacaine as internal standard. The drugs were quantified using a mass spectrometer with an electrospray source in the ESI positive mode (ES+) configured for multiple reaction monitoring. The PD of Nanorap was evaluated with the use of a visual analogue scale. Nanorap was characterized by cryofracture. The chromatography run time was 5.5 min for lidocaine and 3.3 min for prilocaine and the lower limit of quantification was 0.05 ng/mL for both drugs. Mean Cmax was 6.62 and 1.72 ng/mL for lidocaine and prilocaine, respectively. Median Tmax was 6.5 hours for both drugs. Nanocapsules had a mean size of 88nm and mean drug association of 92.5% and 89% for lidocaine and prilocaine, respectively. The PD study showed that Nanorap has a sufficient analgesic effect (>30% reduction in pain) after 10 minutes of application. A new simple, selective and sensitive method for determination of lidocaine and prilocaine in human plasma was developed. Nanorap generated safe plasma levels of the drugs and satisfactory analgesic effect.

Long-term Efficacy And Safety Of Tenofovir Disoproxil Fumarate In Hiv-1-infected Adolescents Failing Antiretroviral Therapy: The Final Results Of Study Gs-us-104-0321.

Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.

Hemodynamic, Ventilatory And Gasometric Evaluation Of An Experimental Bronchopleural Fistula.

To investigate the hemodynamic and ventilatory changes associated with the creation of an experimental bronchopleural fistula (BPF) treated by mechanical ventilation and thoracic drainage with or without a water seal. Six large white pigs weighing 25 kg each which, after general anesthesia, underwent endotracheal intubation (6mm), and mechanically ventilation. Through a left thoracotomy, a resection of the lingula was performed in order to create a BPF with an output exceeding 50% of the inspired volume. The chest cavity was closed and drained into the water sealed system for initial observation of the high output BPF. Significant reduction in BPF output and PaCO2 was related after insertion of a water-sealed thoracic drain, p< 0.05. Insertion of a water-sealed thoracic drain resulted in reduction in bronchopleural fistula output and better CO2 clearance without any drop in cardiac output or significant changes in mean arterial pressure.

Preservation Of The External Jugular Vein In Bilateral Radical Neck Dissections: Technique In Two Cases And Review Of The Literature.

Context. The possibility of cephalic venous hypertension with the resultant facial edema and elevated cerebrospinal fluid pressure continues to challenge head and neck surgeons who perform bilateral radical neck dissections during simultaneous or staged procedures. Case Report. The staged procedure in patients who require bilateral neck dissections allows collateral venous drainage to develop, mainly through the internal and external vertebral plexuses, thereby minimizing the risks of deleterious consequences. Nevertheless, this procedure has disadvantages, such as a delay in definitive therapy, the need for a second hospitalization and anesthesia, and the risk of cutting lymphatic vessels and spreading viable cancer cells. In this paper, we discuss the rationale and feasibility of preserving the external jugular vein. Considering the limited number of similar reports in the literature, two cases in which this procedure was accomplished are described. The relevant anatomy and technique are reviewed and the patients' outcomes are discussed. Conclusion. Preservation of the EJV during bilateral neck dissections is technically feasible, fast, and safe, with clinically and radiologically demonstrated patency.

Predicting Outcomes Of Balloon Laryngoplasty In Children With Subglottic Stenosis.

The treatment of subglottic stenosis in children remains a challenge for the otolaryngologist and may involve procedures such as endoscopy, open surgery, and often both. In the recent past, high-pressure balloons have been used in endoscopic treatment due to their relative facility and high success rates. To report success rates in the treatment of acquired subglottic stenosis with balloon laryngoplasty in children and identify predictive factors for the success of the technique and its complications. Descriptive, prospective study of children who were diagnosed with acquired subglottic stenosis and underwent balloon laryngoplasty as the primary treatment. Balloon laryngoplasty was performed in 48 children with an average age of 20.7 months: 31 presented with chronic subglottic stenosis and 17 with acute stenosis. Success rate was 100% for acute and 39% for chronic subglottic stenosis. Success was significantly associated with several factors, including recently acquired stenosis, initial grade of stenosis, younger patient age, and the absence of tracheotomy. Complications were transitory dysphagia observed in three children and a submucosal cyst in one of the patients. Balloon laryngoplasty may be considered as a first line of treatment for acquired subglottic stenosis. In acute cases, the success rate was 100%, and even though results are less promising in chronic cases, complications were not significant and the patients can undergo open surgery without contraindications. Predictive factors of success were acute stenosis, less severe grades of stenosis, younger patient age, and the absence of tracheotomy.

Aesthetic And Functional Rehabilitation Of The Primary Dentition Affected By Amelogenesis Imperfecta.

The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development.

In Adolescents With Epilepsy, High Scores Of Anxiety And Depression Are Associated With Occurrence Of Seizures In Public Places.

Objective To assess depression and anxiety symptoms of adolescents with epilepsy compared with adolescents without epilepsy. Method The study sample consisted of: case participants (50 subjects) attending the pediatric epilepsy clinic of a tertiary hospital and control participants (51 subjects) from public schools. The instruments utilized were: identification card with demographic and epilepsy data, Beck Depression Inventory and State-Trait Anxiety Inventory. Results No significant differences were founded between the groups regarding scores for depression and anxiety symptoms but both groups presented moderate scores of anxiety. A correlation was found between low scores anxiety and not frequent seizures, low scores anxiety and perception of seizure control, high scores of anxiety and depression and occurrence of seizures in public places. Conclusion Low scores of anxiety are associated with not frequent seizures; high scores of anxiety and depression are associated with occurrence of seizures in public places.

Development Of Egg Pc/cholesterol/α-tocopherol Liposomes With Ionic Gradients To Deliver Ropivacaine.

Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required. This study therefore aimed to provide extended RVC release and increased upload using modified liposomes. Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07 mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5 + (NH4)2SO4 and pH 7.4 + (NH4)2SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4). An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5in) or pH 7.4 with 250 mM (NH4)2SO4 in the inner aqueous core (LMVV 7.4in + ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ∼70%) and sustained release (∼25 h). The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.

Electrocardiogram, Heart Movement And Heart Rate In The Awake Gecko (hemidactylus Mabouia).

The electrocardiogram (ECG) is the simplest and most effective non-invasive method to assess the electrical activity of the heart and to obtain information on the heart rate (HR) and rhythm. Because information on the HR of very small reptiles (body mass <10 g) is still scarce in the literature, in the present work we describe a procedure for recording the ECG in non-anesthetized geckos (Hemidactylus mabouia, Moreau de Jonnès, 1818) under different conditions, namely manual restraint (MR), spontaneous tonic immobility (TI), and in the non-restrained condition (NR). In the gecko ECG, the P, QRS and T waves were clearly distinguishable. The HR was 2.83 ± 0.02 Hz under MR, which was significantly greater (p < 0.001) than the HR under the TI (1.65 ± 0.09 Hz) and NR (1.60 ± 0.10 Hz) conditions. Spontaneously beating isolated gecko hearts contracted at 0.84 ± 0.03 Hz. The in vitro beating rate was affected in a concentration-dependent fashion by adrenoceptor stimulation with noradrenaline, as well as by the muscarinic cholinergic agonist carbachol, which produced significant positive and negative chronotropic effects, respectively (p < 0.001). To our knowledge, this is the first report on the ECG morphology and HR values in geckos, particularly under TI. The methodology and instrumentation developed here are useful for non-invasive in vivo physiological and pharmacological studies in small reptiles without the need of physical restraint or anesthesia.

Dyskinesia induced by phenytoin

Phenytoin is an effective antiepileptic drug, although, it can be associated with many side effects, including dyskinesia. OBJECTIVE: To describe the clinical characteristics of phenytoin induced dyskinesia. METHODS: We investigated the occurrence of involuntary movements in patients followed at our adult and pediatric epilepsy clinics during the period of one year. RESULTS: Three patients presented with phenytoin-induced dyskinesia: one adult with axial and orofacial dyskinesia, and two children with choreoathetosis. They did not have other signs of phenytoin intoxication and had complete recovery after phenytoin withdrawal. CONCLUSION: Phenytoin induced dyskinesia may occur during either chronic or initial treatment and with normal serum phenytoin levels. However, it occurs most often in patients on polytherapy, usually after increasing dosage and with toxic serum levels. Other signs of phenytoin intoxication may be present in these patients, but often the dyskinesia is the only side effect, which may delay the diagnosis and treatment. The clinical characteristics of the involuntary movements vary and may be focal or generalized, most often characterized by choreoathetosis and dyskinesias. These may last for hours, days or even years, but frequently disappear completely after phenytoin withdrawal.

Adaptação de um questionário de autoconfiança relacionado a situações-problema em Odontopediatria

This work describes the adaptation of Milgrom's questionnaire on self-confidence and ways of dealing with behavior problems faced during pediatric dental treatment. The adaptation of the instrument was approved by experts and was analyzed in terms of quantity, coherence and quality of responses. The results of this study suggest that the questionnaire can contribute to dentist's education.

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA). All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine) have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

Endocrinologia pediátrica 2011

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