Efeitos da toxina botulínica do tipo A isolada ou em associação com a finasterida sobre a próstata do cão e rato Sprague-Dawley

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Time needed to schedule dermatological consultations in Brazil

BACKGROUND: It is not clear what the population's demand for dermatologists is, nor how many professionals are needed in order to provide adequate care in this area of expertise. Knowledge of the flow of patients at dermatological clinics throughout the country allows for the formation of expansion and distribution policies regarding professionals, and provides backing for the decision to increase medical residency places. OBJECTIVES: To evaluate the time it takes to schedule a private dermatological consultation in Brazil, and other factors concerning consultations. METHODS: Survey with a random sample of 14% of Brazilian dermatologists, simulating the scheduling of emergency clinical and cosmetic consultations, and botulinum toxin procedures. Also, details relating to cost and professionals, were studied. Data were adjusted for each region of the country. RESULTS: A total of 873 dermatologists were evaluated. Full SBD members represented 85%, and 66% were women. The median time to schedule a consultation ranged from 6 (out-of-pocket payment) to 7 (medical insurance) consecutive working days. Times varied depending on the region. A multivariate analysis showed that out-of-pocket consultations and procedures were scheduled sooner than with medical insurance, regardless of whether they were clinical or cosmetic. CONCLUSION: The characteristics of dermatologists are varied throughout regions of the country. Private consultations and procedures are scheduled sooner than with insurance companies.

Terapéutica alternativa asociada al bruxismo: revisión de literatura

The aim of this study was to review the literature in order to discuss the main and the most effective therapeutic activities to control the nocturnal bruxism. To identify the studies included in this review, it was conducted a detailed and advanced search strategy in the PubMed and Medline databases. It was used as KEY WORDS: bruxism, therapeutics and drug therapy. Inclusion criteria were: case reports, randomized controlled trials, in vitro studies, literature reviews and systematic reviews with or without meta-analysis of the past 10 years that addressed the theme. Exclusion criteria were: articles without abstract, animal studies, articles whose first language was not English and articles from journals that do not belong to the dentario field. From a total of 83 articles, after an analysis according to the inclusion and exclusion criteria, 33 articles were selected. Despite the fact that there is a small number of prospective clinical studies with high degree of reliability and most studies that evaluated the alternative treatments effectiveness are isolated case reports, the current literature shows that the use of botulinum toxin has been shown to be effective in the control of nocturnal bruxism. On the other hand, important aspects such as transitory effect, safe dosage and application technique are still little discussed, then, further studies are needed to have these doubts clarified.

Endoscopic Laser Thyroarytenoid Myoneurectomy in Patients with Adductor Spasmodic Dysphonia: A Pilot Study on Long-Term Outcome on Voice Quality

Objectives. Adductor spasmodic dysphonia (ADSD) is a focal laryngeal dystonia, which compromises greatly the quality of life of the patients involved. It is a severe vocal disorder characterized by spasms of laryngeal muscles during speech, producing phonatory breaks, forced, strained and strangled voice. Its symptoms result from involuntary and intermittent contractions of thyroarytenoid muscle during speech, which causes vocal fold to strain, pressing each vocal fold against the other and increasing glottic resistance. Botulinum toxin injection remains the gold-standard treatment. However, as injections should be repeated periodically leading to voice quality instability, a more definitive procedure would be desirable. In this pilot study we report the long-term vocal quality results of endoscopic laser thyroarytenoid myoneurectomy. Study Design. Prospective study. Methods. Surgery was performed in 15 patients (11 females and four males), aged between 29 and 73 years, diagnosed with ADSD. Voice Handicap Index (VHI) was obtained before and after surgery (median 31 months postoperatively). Results. A significant improvement in VHI was observed after surgery, as compared with baseline values (P = 0.001). The median and interquartile range for preoperative VHI was 99 and 13, respectively and 24 and 42, for postoperative VHI. Subjective improvement of voice as assessed by the patients showed median improvement of 80%. Conclusions. Because long-term follow-up showed significant improvement of voice quality, this innovative surgical technique seems a satisfactory alternative treatment of ADSD patients who seek a definite improvement of their condition.

Quantitative assessment of the intensity of palmar and plantar sweating in patients with primary palmoplantar hyperhidrosis

Objective: To compare individuals with and without hyperhidrosis in terms of the intensity of palmar and plantar sweating. Methods: We selected 50 patients clinically diagnosed with palmoplantar hyperhidrosis and 25 normal individuals as controls. We quantified sweating using a portable noninvasive electronic device that has relative humidity and temperature sensors to measure transepidermal water loss. All of the individuals had a body mass index of 20-25 kg/cm(2). Subjects remained at rest for 20-30 min before the measurements in order to reduce external interference. The measurements were carried out in a climate-controlled environment (21-24 degrees C). Measurements were carried out on the hypothenar region on both hands and on the medial plantar region on both feet. Results: In the palmoplantar hyperhidrosis group, the mean transepidermal water loss on the hands and feet was 133.6 +/- 51.0 g/m(2)/h and 71.8 +/- 40.3 g/m(2)/h, respectively, compared with 37.9 +/- 18.4 g/m(2)/h and 27.6 +/- 14.3 g/m(2)/h, respectively, in the control group. The differences between the groups were statistically significant (p < 0.001 for hands and feet). Conclusions: This method proved to be an accurate and reliable tool to quantify palmar and plantar sweating when performed by a trained and qualified professional.

Dystonic movement disorders and spinal degenerative disease

The occurrence of degenerative spinal disease subsequent to dystonic movement disorders has been neglected and has received more attention only recently. Spinal surgery is challenging with regard to continuous mechanical stress when treatment of the underlying movement disorder is insufficient. To characterize better the particular features of degenerative spinal disease in patients with dystonia and to analyze operative strategies, we reviewed the available published data. Epidemiologic studies reveal that degenerative spinal disorders in patients with dystonia and choreoathetosis occur much earlier than in the physiological aging process. Dystonic movement disorders more often affect the spine at higher cervical levels (C(2-5)), in contrast to spinal degeneration with age which manifests more frequently at the middle and lower cervical spine (C(5-7)). Degenerative changes of the cervical spine are more likely to occur on the side where the chin is rotated or tilted to. Various operative approaches for treatment of spinal pathologies have been advocated in patients with dystonic movement disorders. The available data do not allow making firm statements regarding the superiority of one approach over the other. Posterior approaches were first used for decompression, but additional anterior fusion became necessary in many instances. Anterior approaches with or without instrumented fusion yielded more favorable results, but drawbacks are pseudarthrosis and adjacent-level disease. Parallel to the development of posterior fusion techniques, circumferential surgery was suggested to provide a maximum degree of cord decompression and a higher fusion rate. Perioperative local injections of botulinum toxin were used initially to enhance patient comfort with halo immobilization, but they are also applied in patients without external fixation nowadays. Treatment algorithms directed at the underlying movement disorder itself, taking advantage of new techniques of functional neurosurgery, combined with spinal surgery have recently been introduced and show promising results.

Skin rejuvenation without a scalpel. I. Fillers

Fillers are an important tool in the armamentarium of the physician combating aging phenomena. A wide variety of filler substances are now available that meet many, but by far not all, needs in aesthetic medicine. The most commonly used substances now are hyaluronic acid and collagen preparations that have slightly different indications, but collagen requires pre-use testing to rule out inflammatory complications. Poly-L-lactic acid has gained its place in the filling of adipose tissue wasting in HIV-infected patients. Autologous fat is easy to harvest and inject and has virtually no risk of adverse side effects. Permanent fillers may be of advantage but carry the risk of permanent adverse reactions. Skillful combination of different fillers as well as with botulinum toxin injections and other cosmetic procedures may give optimal results.

Modulation of an early step in the secretory machinery in hippocampal nerve terminals

In hippocampal neurons, neurotransmitter release can be regulated by protein kinase A (PKA) through a direct action on the secretory machinery. To identify the site of PKA modulation, we have taken advantage of the ability of the neurotoxin Botulinum A to cleave the synaptic protein SNAP-25. Cleavage of this protein decreases the Ca2+ responsiveness of the secretory machinery by partially uncoupling Ca2+-sensing from fusion per se. This is expressed as a shift toward higher Ca2+ levels of the Ca2+ to neurotransmitter release relationship and as a perturbation of synaptic delay under conditions where secretion induced by the Ca2+-independent secretagogue ruthenium red is unimpaired. We find that SNAP-25 cleavage also perturbs PKA-dependent modulation of secretion; facilitation of ruthenium red-evoked neurotransmitter release by the adenylyl cyclase activator forskolin is blocked completely after Botulinum toxin A action. Together with our observation that forskolin modifies the Ca2+ to neurotransmitter release relationship, our results suggest that SNAP-25 acts as a functional linker between Ca2+ detection and fusion and that PKA modulates an early step in the secretory machinery related to calcium sensing to facilitate synaptic transmission.

Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion

The membrane protein syntaxin participates in several protein–protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse.

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

Using adenoviruses encoding reporter genes as retrograde tracers, we assessed the capacity of motoneurons to take up and retrogradely transport adenoviral particles injected into the muscles of transgenic mice expressing the G93A human superoxide dismutase mutation, a model of amyotrophic lateral sclerosis. Surprisingly, transgene expression in the motoneurons was significantly higher in symptomatic mice than in control or presymptomatic mice. Using botulinum toxin to induce nerve sprouting at neuromuscular junctions, we showed that the unexpectedly high level of motoneurons retrograde transduction results, at least in part, from newly acquired uptake properties of the sprouts. These findings demonstrate the remarkable uptake properties of amyotrophic lateral sclerosis motoneurons in response to denervation and the rationale of using intramuscular injections of adenoviruses to overexpress therapeutic proteins in motor neuron diseases.

Bexiga hiperactiva e utilização de toxina botulínica na hiperactividade do detrusor : resultados obtidos pelo Serviço de Urologia do HSM-CHLN

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

BDNF-TrkB Signaling in Single-Spine Structural Plasticity

Multiple lines of evidence reveal that activation of the tropomyosin related kinase B (TrkB) receptor is a critical molecular mechanism underlying status epilepticus (SE) induced epilepsy development. However, the cellular consequences of such signaling remain unknown. To this point, localization of SE-induced TrkB activation to CA1 apical dendritic spines provides an anatomic clue pointing to Schaffer collateral-CA1 synaptic plasticity as one potential cellular consequence of TrkB activation. Here, we combine two-photon glutamate uncaging with two photon fluorescence lifetime imaging microscopy (2pFLIM) of fluorescence resonance energy transfer (FRET)-based sensors to specifically investigate the roles of TrkB and its canonical ligand brain derived neurotrophic factor (BDNF) in dendritic spine structural plasticity (sLTP) of CA1 pyramidal neurons in cultured hippocampal slices of rodents. To begin, we demonstrate a critical role for post-synaptic TrkB and post-synaptic BDNF in sLTP. Building on these findings, we develop a novel FRET-based sensor for TrkB activation that can report both BDNF and non-BDNF activation in a specific and reversible manner. Using this sensor, we monitor the spatiotemporal dynamics of TrkB activity during single-spine sLTP. In response to glutamate uncaging, we report a rapid (onset less than 1 minute) and sustained (lasting at least 20 minutes) activation of TrkB in the stimulated spine that depends on N-methyl-D-aspartate receptor (NMDAR)-Ca2+/Calmodulin dependent kinase II (CaMKII) signaling as well as post-synaptically synthesized BDNF. Consistent with these findings, we also demonstrate rapid, glutamate uncaging-evoked, time-locked release of BDNF from single dendritic spines using BDNF fused to superecliptic pHluorin (SEP). Finally, to elucidate the molecular mechanisms by which TrkB activation leads to sLTP, we examined the dependence of Rho GTPase activity - known mediators of sLTP - on BDNF-TrkB signaling. Through the use of previously described FRET-based sensors, we find that the activities of ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) require BDNF-TrkB signaling. Taken together, these findings reveal a spine-autonomous, autocrine signaling mechanism involving NMDAR-CaMKII dependent BDNF release from stimulated dendritic spines leading to TrkB activation and subsequent activation of the downstream molecules Rac1 and Cdc42 in these same spines that proves critical for sLTP. In conclusion, these results highlight structural plasticity as one cellular consequence of CA1 dendritic spine TrkB activation that may potentially contribute to larger, circuit-level changes underlying SE-induced epilepsy.

Tooth Mobility, Periodontal Ligament Space, and the Alveolus During Periodontal Health, Disease, and Disuse

Thesis (Ph.D.)--University of Washington, 2016-07

OnabotulinumtoxinA for hemicrania continua: open label experience in 9 patients

BACKGROUND: Hemicrania continua is a strictly unilateral, continuous headache, typically mild to moderate in severity, with severe exacerbations commonly accompanied by cranial autonomic features and migrainous symptoms. It is exquisitely responsive to Indomethacin. However, some patients cannot tolerate treatment, often due to gastrointestinal side effects. Therapeutic alternatives are limited and controlled evidence lacking. METHODS: We present our experience of nine patients treated with OnabotulinumtoxinA for hemicrania continua. All patients were injected using the PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) protocol for migraine. RESULTS: Five of nine patients demonstrated a 50% or more reduction in moderate to severe headache days with OnabotulinumtoxinA with a median reduction in moderate to severe headache days of 80%. Patient estimate of response was 80% or more in five subjects. The median and mean duration of response in the five responders was 11 and 12 weeks (range 6-20 weeks). Improvements were also seen in headache-associated disability CONCLUSIONS: OnabotulinumtoxinA adds a potential option to the limited therapeutic alternatives available in hemicrania continua.

Vector analysis of porosity evidences bone loss at the epiphysis in the BTX rat model of disuse osteoporosis

International audience