Thesis (Ph. D.)--University of Sydney, 1999. / Title from title screen (viewed Apr. 21, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Dept. of Anaesthesia and Pain Management, Faculty of Medicine. Includes bibliography. Also available in print form.

Thesis (M. Sc. Med.)--University of Sydney, 2001. / Title from title screen (viewed Apr. 23, 2008). Submitted in fulfilment of the requirements for the degree of Master of Science in Medicine to the Dept. of Anaesthesia and Pain Management, Faculty of Medicine. Includes bibliography. Also available in print form.

The delicate anatomical structures involved in infant cry production require intricate neurophysiological control especially in premature infants or those with a reduced respiratory or laryngeal function. Certain features like phonatory noise or subharmonics can be observed in infant cries using spectrograms. These features have a certain indicative valence for characterising the maturation stage of vocal control or its performance. One possible cause of deviation in neurophysiological coordination during voice production is disturbed CNS mechanisms, finally the consequences of orofacial clefts. Another is the influence of a familiar disposition for speech development disorders. The present paper studied the latter two relationships. For the evaluation and interpretation of a noise index (= average value of the noise portion within a cry) in infant’s pre-speech utterances, we analysed 1423 voice-signals emitted during the first 15 weeks of life by 10 orofacial cleft infants (5 females and 5 males), comparing these with a control group. The control group B of healthy infants was subdivided into B1 (FH- infants with a negative family history of speech developmental disorders) and B2 (FH+ infants with a positive family history of speech developmental disorders). Infants born with orofacial clefts are substantially exposed to severe difficulties for speech and language acquisition. Coupled with a premature muscle network, cleft infants are deprived in various ways (vocal nasality, limited consonant repertetoire, backward articulation etc) and their coordination of respiration, phonation and articulation is limited from a very early age. From birth until about 2 months of age, an infant's cry is characterised by a tuning phase between respiration and phonation. After training the production of more complex cry melodies with different rhythms, infants begin at 3 - 4 months of age (Wermke et al., 2005) to tune their phonation and articulation. Successfully absolving these stages of development is presumably a prerequisite for later acquisition of inconspicuous speech and language competence. The development of articulation is based on the tuning of melodies produced in the larynx and resonant frequencies from the vocal tract (Kempf, 2008). For an objective evaluation of pre-speech development in healthy and sick infants, this study produced comparable data on the appearance of selected parameters in age-appropriate control groups. In order to examine the connection between these selected cry properties and the physiological condition in infants, we made comparisons to 2623 voice-signals from 10 FH+ infants and 3002 voice-signals from 10 FH- infants (all without orofacial clefts and age-appropriates). For interpretations of future results, we also analysed 2684 voice-signals from 4 infants in the control group B1 (FH-) taken at closer time intervals until the 20th week of life. This study showed that the appearance of noise-like elements (NI) in the vocalizations of orofacial cleft infants and FH+ infants were identical during the first 15 weeks of life. Also, we could show that in both these groups (A and B2) there was a delayed development in the average signal length (phonation time). Although cleft infants and FH+ infants differ from each other physiologically, our results may propose a common neurophysiological retardation. Comparing prosodic elements in cries from FH+ and FH- infants showed differences (Blohm, 2007; Denner, 2007). Therefore, future research could apply this knowledge to a larger sample of infants in order to establish a better therapy concept, thus preventing late interventions. Infants from our control group B1 (FH-) met our expectations because when they got older, a development in their pre-speech capability was noticed. Our results support the hypothesis that in cry research, physiological differences (orofacial clefts or a family history for speech development disorders) in infants may encourage the appearance of noise-like elements in their vocalisations. However we believe that a period of training enables the infants to reduce their mean NI. The production of more complex melodies with age was better managed by the FH- infants and they also produced longer cries. To avoid a developmental retardation in speech and learning capabilities, it may be necessary in future to make more compact studies considering many other parameters and making comparisons with age-appropriates. Further studies also have to correlate these findings while investigating the consequences of these maturation processes on sound production. Despite physiological differences in the three groups of infants, the noise index (NI) as applied in this study can be used as an objective parameter for daily clinical diagnosis during the first four months of life. / Säuglinge mit einer orofazialen Spaltbildung sind bezüglich vieler Aspekte in ihrer sprachlichen Entwicklung benachteiligt (hypernasale Resonanz, eingeschränktes Konsonantenrepertoire, Rückverlagerung der Artikulation usw.) sowie bei der Koordination von Respiration, Phonation und Artikulation vor der chirurgische Behandlung. Ab Geburt bis zum Alter von 2 Monaten sind Säuglingslaute durch ausgeprägte Frequenzmodulationen charakterisiert, die auf einer Abstimmung von Respiration und Phonation beruhen. Nachdem Säuglinge in den ersten Wochen die Produktion komplexer Schrei-Melodien mit unterschiedlichen Rhythmen geübt haben, beginnen sie im Alter zwischen 3 - 4 Monaten die Phonation und die Artikulation fein abzustimmen (Wermke et al., 2005). Das erfolgreiche Absolvieren dieser Entwicklungsstadien ist möglicherweise eine Voraussetzung für einen späteren unauffälligen Sprech- und Spracherwerb. Die Artikulation beginnt sowohl mit einen intentionalen Tuning der Melodien, die laryngeal erzeugt werden, als auch mit der Bildung von Resonanzfrequenzen des Vokaltraktes (Kempf, 2008). Diese Entwicklungsprozesse sind bei Säuglingen mit orofazialen Spaltbildungen gestört. Die erhöhte nasale Impedanz führt durch einen rückgekoppelten Regelkreis zu einem Anstieg des subglottischen Druckes (Hauschildt, 2006). Die winzigen Stimmlippen der jungen Säuglinge sind diesem Druck nicht ausreichend gewachsen, so dass es regelmäßig zu phonatorischen Rauschphänomenen in deren erzeugten Lauten kommt. Dies verhindert das "Trainieren" melodisch-rhythmischer Elemente als Vorstufe für die spätere muttersprachliche Prosodie. Für eine objektive Auswertung solcher Phänomene in den vorsprachigen Entwicklungen wurden in dieser Studie das Auftreten und der Grad ihrer Ausprägung anhand ausgesuchter Parameter bei Säuglingen mit orofazialen Spalten (Gruppe A)) und bei solchen in einer altersähnlichen Kontrollgruppe (B) untersucht. Die Kontrollgruppe B bestand aus gesunden Säuglingen ohne (FH- oder B1) bzw. mit (FH+ oder B2) einem familiären Risiko für eine spezifische Spracherwerbsstörung. Letztere wurden einbezogen, da Säuglinge mit orofazialen Spalten (A) und Säuglinge mit einer familiären Disposition für Spracherwerbsstörungen (FH+) ähnlichen Abweichungen in der neurophysiologische Koordination der Lautproduktion aufweisen (Denner, 2007). In der Kontrollgruppe wurden 2623 einzelne Laute von 10 FH+ Kindern und 3002 Laute von 10 FH- Kindern miteinander verglichen. Um Entwicklungstrends besser beurteilen zu können, wurden in dichteren Intervallen (wöchentlich statt monatlich) 2686 Laute aus der Gruppe B1 (FH-) bis zur 20 Lebenswoche analysiert. Diese Studie konnte zeigen, dass während der ersten 15 Lebenswochen sehr identische, geräuschähnliche Phänomene (RI) in der Vokalisation von Spaltkindern und FH+ Kindern auftreten. Außerdem konnte gezeigt werden, dass in diesen beiden Gruppen eine verzögerte Entwicklung der durchschnittlichen Signallänge (Phonationszeit) einzelner Laute auftrat. Trotz allen physiologischen Unterschieden zwischen den Spaltkindern und den FH+ Kindern deuten unsere Ergebnisse auf eine gemeinsame neurophysiologische Entwicklungsverzögerung hin. Ein Vergleich prosodischer Elemente in der Vokalisationen von älteren FH+ und FH- Kindern ergab auch Unterschiede (Blohm, 2007; Denner, 2007). Die vorliegende Studie bestätigt dies und die Erkenntnisse könnten zukünftig verwendet werden um geeignete Therapieverfahren zu entwickeln. Säuglinge aus der Kontrollegruppe B1 (FH-) bestätigen die gestellten Hypothesen, da mit zunehmendem Alter eine signifikante Reduktion von Rauschphänomenen beobachtet wurde. Keine andere Studie hat bis heute eine vergleichbare objektive und detaillierte Analyse der Rauschelemente in Säuglingslauten durchgeführt. Die Ergebnisse bestätigen die Hypothese, dass neurophysiologische Besonderheiten, die auf eine orofaziale Spalte oder eine familiäre Disposition für eine Spracherwerbsstörung zurückzufuhren sind, das Auftreten von rauschähnlichen Elementen in der Vokalisation von Säuglingen beeinflussen könnten. Ganz offenbar gehört eine 'Trainingphase' dazu, um den mittlere RI zu reduzieren. Komplexere Melodien konnten mit zunehmendem Alter von den FH- Kindern besser beherrscht werden, da sie wohl auch längere Schreie koordinierter erzeugten. Die Arbeit bestätigt auch, dass der Rauschindex (RI), wie er in dieser Studie angewandt wurde, geeignet ist, um bei der klinischen Betreuung von orofazialen Spaltkindern, insbesondere während der ersten vier Lebensmonate, als Entwicklungsstandindikator dienen kann. Um einem Entwicklungsrückstand in der Spracherwerbsfähigkeit gefährdeter Säuglinge zu belegen, wird es in Zukunft nötig sein, umfassendere Studien durchzuführen, wobei weitere akustische Parameter berücksichtigt werden sollten.

O objetivo deste estudo foi avaliar a atividade elétrica dos músculos da mímica de pacientes com dor muscular mastigatória utilizando eletromiografia de superfície. Foram avaliadas 15 mulheres com dor muscular mastigatória (idade média de 33.4, variando de 22-44), grupo de estudo (GMM) e 21 mulheres (idade média de 28.5, variando de 21-45), do grupo controle (GC) Foram realizadas avaliação clínica fonoaudiológica e eletromiográfica (eletromiógrafo ADS 1200, da Lynx Tecnologia Eletrônica Ltda, eletrodos de disco de prata, descartáveis, gel condutor, auto-adesivos com 10mm de diâmetro por HAL Ind. e Com. LTDA) dos músculos: orbicular dos lábios, bucinador, supra-hióideos e masseter em repouso e nos movimentos: protrusão dos lábios, apertamento dos lábios, inflar bochechas, sorriso fechado e sorriso aberto. Houve diferença significativa entre os grupos: os valores da eletromiografia de repouso foram inferiores para o músculo masseter direito (p=0.012) e esquerdo (p=0.019); nos movimentos, os valores eletromiográficos foram superiores no grupo controle durante os movimentos: protrusão dos lábios bucinador esquerdo (p=0.005); suprahióideo esquerdo (p=0.011); apertamento dos lábios bucinador esquerdo (p=0.005); bucinador direito (p=0.007); supra-hióideo esquerdo (p=0.046); supra-hióideo direito (p=0.039); orbicular superior (p=0.042); inflar as bochechas masseter esquerdo (p=0.021); bucinador esquerdo (p=0.007); bucinador direito (p=0.002); orbicular superior (p=0.039); sorriso fechado masseter esquerdo (p=0.004); masseter direito (p=0.019); bucinador esquerdo (p=0.013); supra-hióideo esquerdo (p=0.046) e no sorriso aberto masseter esquerdo (p=0.030). Desta forma, o músculo de maior atividade eletromiográfica foi o orbicular da boca. No repouso, os valores foram inferiores para o masseter e superiores para os demais músculos e nos movimentos, os valores foram superiores em todos os músculos para o grupo de estudo / The objective this study is assess the electric activity of mimic muscles in patients with masticatory muscle pain using surface electromyography (EMG). Was evaluated 15 women with masticatory muscle pain (mean age 33.4, ranging between 22 44 years old), study group (GMM) and 21 women (mean age 28.5, ranging between 21 45 years old), control group (CG). Clinical phonoaudiological and electromyographic assessments were performed (electromyograph ADS 1200 of Lynx Tecnologia Eletrônica Ltda, 10mm disposable pregelled self-adhesive silver disk electrodes of HAL Ind. e Com. LTDA) in the muscles: orbicularis oris, buccinator, suprahyoid and masseter, both at rest and in movement: lip protrusion, lip contraction, cheek inflation, close smile and open smile. There was significant difference between the groups: the values of the electromyography at rest were lower for the right and left masseter muscle (p=0.012 and p=0.019, respectively); in movement, the eletromyographic values were higher in the group control during movement: lip protrusion right buccinator (p=0.005); left suprahyoid (p=0.011); lip contraction left buccinator (p=0.005); right buccinator (p=0.007); left suprahyoid (p=0.046); right suprahyoid (p=0.039); orbicularis oris (p=0.042); cheek inflation left masseter (p=0.021); left buccinator (p=0.007); right buccinator (p=0.002); orbicularis oris (p=0.039); closed smile left masseter (p=0.004); right masseter (p=0.019); left buccinator (p=0.013); left suprahyoid (p=0.046); open smile left masseter (p=0.030). Thus, the orbicularis oris muscle presented the highest EMG activity. At rest, the values were lower for the masseter and higher for the other muscles and, in movement, the values were higher for all the muscles in the study group

O objetivo deste estudo foi avaliar a atividade elétrica dos músculos da mímica de pacientes com dor muscular mastigatória utilizando eletromiografia de superfície. Foram avaliadas 15 mulheres com dor muscular mastigatória (idade média de 33.4, variando de 22-44), grupo de estudo (GMM) e 21 mulheres (idade média de 28.5, variando de 21-45), do grupo controle (GC) Foram realizadas avaliação clínica fonoaudiológica e eletromiográfica (eletromiógrafo ADS 1200, da Lynx Tecnologia Eletrônica Ltda, eletrodos de disco de prata, descartáveis, gel condutor, auto-adesivos com 10mm de diâmetro por HAL Ind. e Com. LTDA) dos músculos: orbicular dos lábios, bucinador, supra-hióideos e masseter em repouso e nos movimentos: protrusão dos lábios, apertamento dos lábios, inflar bochechas, sorriso fechado e sorriso aberto. Houve diferença significativa entre os grupos: os valores da eletromiografia de repouso foram inferiores para o músculo masseter direito (p=0.012) e esquerdo (p=0.019); nos movimentos, os valores eletromiográficos foram superiores no grupo controle durante os movimentos: protrusão dos lábios bucinador esquerdo (p=0.005); suprahióideo esquerdo (p=0.011); apertamento dos lábios bucinador esquerdo (p=0.005); bucinador direito (p=0.007); supra-hióideo esquerdo (p=0.046); supra-hióideo direito (p=0.039); orbicular superior (p=0.042); inflar as bochechas masseter esquerdo (p=0.021); bucinador esquerdo (p=0.007); bucinador direito (p=0.002); orbicular superior (p=0.039); sorriso fechado masseter esquerdo (p=0.004); masseter direito (p=0.019); bucinador esquerdo (p=0.013); supra-hióideo esquerdo (p=0.046) e no sorriso aberto masseter esquerdo (p=0.030). Desta forma, o músculo de maior atividade eletromiográfica foi o orbicular da boca. No repouso, os valores foram inferiores para o masseter e superiores para os demais músculos e nos movimentos, os valores foram superiores em todos os músculos para o grupo de estudo / The objective this study is assess the electric activity of mimic muscles in patients with masticatory muscle pain using surface electromyography (EMG). Was evaluated 15 women with masticatory muscle pain (mean age 33.4, ranging between 22 44 years old), study group (GMM) and 21 women (mean age 28.5, ranging between 21 45 years old), control group (CG). Clinical phonoaudiological and electromyographic assessments were performed (electromyograph ADS 1200 of Lynx Tecnologia Eletrônica Ltda, 10mm disposable pregelled self-adhesive silver disk electrodes of HAL Ind. e Com. LTDA) in the muscles: orbicularis oris, buccinator, suprahyoid and masseter, both at rest and in movement: lip protrusion, lip contraction, cheek inflation, close smile and open smile. There was significant difference between the groups: the values of the electromyography at rest were lower for the right and left masseter muscle (p=0.012 and p=0.019, respectively); in movement, the eletromyographic values were higher in the group control during movement: lip protrusion right buccinator (p=0.005); left suprahyoid (p=0.011); lip contraction left buccinator (p=0.005); right buccinator (p=0.007); left suprahyoid (p=0.046); right suprahyoid (p=0.039); orbicularis oris (p=0.042); cheek inflation left masseter (p=0.021); left buccinator (p=0.007); right buccinator (p=0.002); orbicularis oris (p=0.039); closed smile left masseter (p=0.004); right masseter (p=0.019); left buccinator (p=0.013); left suprahyoid (p=0.046); open smile left masseter (p=0.030). Thus, the orbicularis oris muscle presented the highest EMG activity. At rest, the values were lower for the masseter and higher for the other muscles and, in movement, the values were higher for all the muscles in the study group

M.Tech.

A dor é um importante sintoma que sinaliza danos teciduais ou agentes potencialmente prejudiciais ao organismo, evocando respostas sensoriais e motoras de proteção. A dor orofacial apresenta alta prevalência na sociedade atual, sendo esta condição associada a tecidos duros e moles da cabeça, face, pescoço e a estruturas intraorais. Considerando as dores orofaciais de origem músculo-esquelética, destacam-se àquelas causadas pela Disfunção Temporomandibular (DTM). A DTM apresenta etiologia multifatorial, caracterizada por quadros crônicos envolvendo a região cervical, a musculatura mastigatória e a articulação temporomandibular (ATM). Desde que a inflamação das ATMs é considerada a principal causa da dor em pacientes portadores de DTM, a busca por novas opções terapêuticas para esta disfunção envolve estudos desta articulação, abrangendo aspectos fisiológicos, morfológicos e moleculares. Considerando o processo inflamatório e os aspectos moleculares envolvidos no desenvolvimento desta condição, é possível que as enzimas proteolíticas extracelulares, destacando-se as Metaloproteinases da Matriz (MMPs), as quais estão envolvidas na reabsorção de colágeno e de outras macromoléculas, tenham participação ativa neste processo. Em particular, estudos demonstraram que as MMPs estão envolvidas na modulação da dor neuropática, bem como estão presentes no líquido sinovial de portadores de inflamação da ATM. Sendo assim, o objetivo deste trabalho foi avaliar a influência da administração do Adjuvant de Freund (CFA) intraarticular, bilateralmente nas ATMs de ratos, na sensibilidade mecânica e nociceptiva, bem como avaliar a expressão das MMPs, em particular da MMP-2 e MMP-9, no gânglio trigeminal, nas diferentes fases de desenvolvimento da inflamação. Os resultados mostraram que a inflamação das ATMs promoveu alodinia mecânica e hiperalgesia orofacial. Em adição, a administração de doxiciclina (inibidor inespecífico das MMPs) reduziu as alterações na sensibilidade mecânica e nociceptiva. A quantificação das MMPs no gânglio trigeminal demonstrou que o início da inflamação promove aumento da MMP-9 (1 e 3 dias), enquanto que nas fases tardias do processo inflamatório acompanha-se o aumento da expressão da MMP-2 (3, 7 e 10 dias). / Pain is an important symptom that signals tissue damage or potentially harmful agents to the body and evokes sensory and motor protection. The orofacial pain is a type of symptoms that appears in high prevalence in modern society. This painful condition is associated with hard and soft tissues of the head, face, neck and intraoral structures. Considering the pain of musculoskeletal origin, we can highlight those caused by temporomandibular dysfunction (TMD). The TMD has a multifactorial etiology, characterized primarily by chronic conditions involving the neck, the chewing muscles and temporomandibular joint (TMJ). Inflammation of the TMJ is considered the main cause of pain in patients with TMD. Thus, the search for new therapeutic options for this disorder involves studies in the TMJ region encompassing physiological, morphological and molecular aspects. Considering the inflammatory process as the main cause of pain present in TMD, it is extremely important to understand the molecular aspects involved in developing this condition. In this context, extracellular proteolytic enzymes, highlighting the metaloproteniases matrix metalloproteinases (MMPs) play major role in the resorption of collagen and other macromolecules. The proteolytic activity of these MMPs is controlled by tissue inhibitors of metalloproteinases (TIMPs), which contribute to the maintenance of metabolic balance and structure of the extracellular matrix. Therefore, the objective of this study was to assess whether the type MMP gelatinases (MMP-2 and MMP-9) of the trigeminal ganglion participate in the development of mechanical allodynia and hyperalgesia in rats orofacial chronic inflammation bilateral TMJ. Our results demonstrated the presence of orofacial hyperalgesia, as well as mechanical allodynia in animals with temporomandibular inflammation induced by CFA and an increase in the expression and activity of gelatinases in the trigeminal ganglion of these animals. Still, there was a decrease in nociceptive orofacial hipersensitivity in animals that received a non-specific inhibitor for MMPs (doxycycline, 30mg/kg/day) for 10 days.

A dor é um importante sintoma que sinaliza danos teciduais ou agentes potencialmente prejudiciais ao organismo, evocando respostas sensoriais e motoras de proteção. A dor orofacial apresenta alta prevalência na sociedade atual, sendo esta condição associada a tecidos duros e moles da cabeça, face, pescoço e a estruturas intraorais. Considerando as dores orofaciais de origem músculo-esquelética, destacam-se àquelas causadas pela Disfunção Temporomandibular (DTM). A DTM apresenta etiologia multifatorial, caracterizada por quadros crônicos envolvendo a região cervical, a musculatura mastigatória e a articulação temporomandibular (ATM). Desde que a inflamação das ATMs é considerada a principal causa da dor em pacientes portadores de DTM, a busca por novas opções terapêuticas para esta disfunção envolve estudos desta articulação, abrangendo aspectos fisiológicos, morfológicos e moleculares. Considerando o processo inflamatório e os aspectos moleculares envolvidos no desenvolvimento desta condição, é possível que as enzimas proteolíticas extracelulares, destacando-se as Metaloproteinases da Matriz (MMPs), as quais estão envolvidas na reabsorção de colágeno e de outras macromoléculas, tenham participação ativa neste processo. Em particular, estudos demonstraram que as MMPs estão envolvidas na modulação da dor neuropática, bem como estão presentes no líquido sinovial de portadores de inflamação da ATM. Sendo assim, o objetivo deste trabalho foi avaliar a influência da administração do Adjuvant de Freund (CFA) intraarticular, bilateralmente nas ATMs de ratos, na sensibilidade mecânica e nociceptiva, bem como avaliar a expressão das MMPs, em particular da MMP-2 e MMP-9, no gânglio trigeminal, nas diferentes fases de desenvolvimento da inflamação. Os resultados mostraram que a inflamação das ATMs promoveu alodinia mecânica e hiperalgesia orofacial. Em adição, a administração de doxiciclina (inibidor inespecífico das MMPs) reduziu as alterações na sensibilidade mecânica e nociceptiva. A quantificação das MMPs no gânglio trigeminal demonstrou que o início da inflamação promove aumento da MMP-9 (1 e 3 dias), enquanto que nas fases tardias do processo inflamatório acompanha-se o aumento da expressão da MMP-2 (3, 7 e 10 dias). / Pain is an important symptom that signals tissue damage or potentially harmful agents to the body and evokes sensory and motor protection. The orofacial pain is a type of symptoms that appears in high prevalence in modern society. This painful condition is associated with hard and soft tissues of the head, face, neck and intraoral structures. Considering the pain of musculoskeletal origin, we can highlight those caused by temporomandibular dysfunction (TMD). The TMD has a multifactorial etiology, characterized primarily by chronic conditions involving the neck, the chewing muscles and temporomandibular joint (TMJ). Inflammation of the TMJ is considered the main cause of pain in patients with TMD. Thus, the search for new therapeutic options for this disorder involves studies in the TMJ region encompassing physiological, morphological and molecular aspects. Considering the inflammatory process as the main cause of pain present in TMD, it is extremely important to understand the molecular aspects involved in developing this condition. In this context, extracellular proteolytic enzymes, highlighting the metaloproteniases matrix metalloproteinases (MMPs) play major role in the resorption of collagen and other macromolecules. The proteolytic activity of these MMPs is controlled by tissue inhibitors of metalloproteinases (TIMPs), which contribute to the maintenance of metabolic balance and structure of the extracellular matrix. Therefore, the objective of this study was to assess whether the type MMP gelatinases (MMP-2 and MMP-9) of the trigeminal ganglion participate in the development of mechanical allodynia and hyperalgesia in rats orofacial chronic inflammation bilateral TMJ. Our results demonstrated the presence of orofacial hyperalgesia, as well as mechanical allodynia in animals with temporomandibular inflammation induced by CFA and an increase in the expression and activity of gelatinases in the trigeminal ganglion of these animals. Still, there was a decrease in nociceptive orofacial hipersensitivity in animals that received a non-specific inhibitor for MMPs (doxycycline, 30mg/kg/day) for 10 days.

Submitted by Pedro Barros (pedro.silvabarros@ufpe.br) on 2018-09-13T21:02:45Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TESE Danielle Rocha do Val.pdf: 2561298 bytes, checksum: 87a6411a7d7f0d8d8a4e52ec8cebcd8e (MD5) / Approved for entry into archive by Alice Araujo (alice.caraujo@ufpe.br) on 2018-09-18T14:59:12Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TESE Danielle Rocha do Val.pdf: 2561298 bytes, checksum: 87a6411a7d7f0d8d8a4e52ec8cebcd8e (MD5) / Made available in DSpace on 2018-09-18T14:59:12Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TESE Danielle Rocha do Val.pdf: 2561298 bytes, checksum: 87a6411a7d7f0d8d8a4e52ec8cebcd8e (MD5) Previous issue date: 2017-03-03 / FACEPE / As disfunções temporomandibulares (DTM) abrangem uma série de problemas clínicos que envolvem os músculos mastigatórios e/ou articulação temporomandibular (ATM) e estruturas associadas, sendo a segunda fonte mais comum de dor orofacial. Apesar da farmacoterapia diversa para tratamento das DTMs, nenhuma das intervenções terapêuticas disponíveis na atualidade é curativa, limitando-se, portanto a aliviar os sinais e sintomas da doença. Avaliar a segurança e a atividade antinociceptiva e anti-inflamatória de um composto semissintético derivado de Tephrosia toxicaria Pers. Realizou-se processo de hidrogenação da 5- hidroxi-6”,6”-dimetilcromeno-[2”,3”:7,8]-flavanona para obtenção 5-hidroxi-6”,6”-dimetilcromano-[2”,3”:7,8]-flavanona (PHO). Para avaliar os efeitos sistêmicos da administração subaguda, camundongos machos e fêmeas receberam diariamente PHO (10 μg/kg; per.os ou i.p.) durante 14 dias. O grupo controle recebeu solução salina durante o mesmo período. No 15º dia foi realizada eutanásia para avaliação de parâmetros bioquímicos e posterior análise histopatológica dos órgãos. Na toxicidade aguda camundongos machos e fêmeas em jejum receberam PHO (1, 10 e 100 mg/kg; per.os ou i.p.) ou solução salina, e foram observados por um período de 48 h. Para avaliação se o efeito farmacológico da PHO (10 μg/kg; per.os) interferia na atividade motora dos animais foi realizado o teste do rota rod em ratos. Avaliou-se ainda o efeito anti-inflamatório e antinociceptivo de PHO no modelo de hipernocicepção inflamatória induzida por formalina na ATM. Ratos foram pré-tratados (per.os.) com PHO (0,1, 1 ou 10 μg/kg) 60 min antes da injeção de formalina (1,5%) intraarticular (i.art.). O grupo Sham recebeu solução salina (i.art.) e o grupo Formalina recebeu formalina (1,5%) (i.art.). A resposta comportamental nociceptiva foi avaliada durante um período de observação de 45 min. Os tecidos periarticulares foram coletados para dosagem de TNF-α, IL-1β, IL-8, IL-10 pelo método ELISA e avaliação da expressão de ICAM-1 e CD55. Além disso, foram realizados os ensaios da análise da permeabilidade vascular. Em outra série de experimentos investigamos o envolvimento da via HO-1 e NO/GMPc/PKG/K+ATP no efeito antinoceceptivo de PHO. A partir do processo de hidrogenação, obteve-se 5-hidroxi-6”,6”-dimetilcromano-[2”,3”:7,8]-flavanona (PHO) que gerou o depósito de patente do nosso grupo sob número de registro: BR1020130287938 no INPI. PHO 10 μg/kg durante 14 dias não alterou a variação ponderal, o peso úmido dos órgãos e parâmetros bioquímicos em relação ao grupo salina. No teste de toxicidade aguda não ocorreu nenhuma morte em todas as doses administradas.No teste do Rota-rod não houve alteração motora nos grupos tratados com o composto. PHO 10 μg/kg) reduziu (p <0,05) a hipernocicepção inflamatória, quando comparado ao grupo formalina. Reduziu o extravasamento plasmático, os níveis TNF-α, IL-1β, IL-8 e aumentou IL-10 nos tecidos periarticulares quando comparado ao grupo formalina (p <0,05). A expressão de ICAM-1 e CD55 foi reduzida após a administração de PHO quando comparado ao grupo não tratado (p <0,05). O efeito antinociceptivo de PHO é multimodal, não atuando pela via do HO-1/GMPc/PKG, porém dependendo da integridade das vias do NO e canais K⁺ sensíveis a ATP. PHO posssui atividade antinociceptiva e anti-inflamatória, Não apresentando toxicidade, com valor biotecnológico para o tratamento de dor orofacial. / Temporomandibular disorders (TMD) encompass clinical conditions involving masticatory muscles and/or the temporomandibular joint (TMJ) as well as the associated structures. Even with the drug therapy available for the TMD treatment, none of the interventions are definitive since the treatments only relieve the symptoms associated with these disorders. To evaluate the safety, antinociceptive and anti-inflammatory activities of a semi-synthetic molecule derived from Tephrosia toxicaria Pers. 5-hydroxy-6”,6”-dimethyl chroman-[2”,3”:7,8]-flavone underwent hydrogenation, producing 5-hydroxy-6”,6”-dimethyl chromone - [2”,3”:7,8]-flavone (PHO). To evaluate systemic effects, male and female mice received daily PHO (10 μg/kg; per.os or i.p.) for 14 days. Negative control groups received saline solution. Animals were euthanised on day 15 to assess biochemical parameters and histopathological analysis of the organs. In the acute toxicity assay, male and female received PHO (10 μg/kg; per.os or i.p.) or saline solution, and were observed for 48 hours. PHO (10 μg/kg; per.os) was also assayed for motor impairment in the rota-rod test in rats. The anti-inflammatory and antinociceptive effects of PHO were assayed in the formalin-induced TMJ inflammatory hypernociception. Rats were pre-treated (per.os.) with PHO (0.1, 1 or 10 μg/kg) 60 min before intra-articular formalin (1.5%) injection. Sham groups received saline solution intra-articular injection. Nociceptive responses were evaluated during 45 minutes. Periarticular tissues were excised for TNF-α, IL-1β, IL-8, IL-10 levels (ELISA) and ICAM-1/CD55 expression. Further, the Evans blue vascular permeability assay was carried out. In another series of experiments, we investigated the involvement of the HO-1 and NO/GMPc/PKG/K+ATP pathways in the PHO nociceptive effects. 5-hydroxy-6”,6”-dimethyl chromone - [2”,3”:7,8]-flavone was patented under the registration number (BR1020130287938) at INPI. PHO 10 μg/kg did not alter body mass, wet organ weight, and biochemical parameters after 14 days. In the acute toxicity test, no death episode occurred at the tested doses. The rota-rod test showed no motor impairment. PHO (10 μg/kg) reduced (p<0.05) inflammatory hypernociception, vascular permeability, TNF-α, IL-1β, IL-8 levels, and promoted IL-10 level increase in the periarticular tissues. ICAM-1/CD55 expression was reduced after PHO administration. The PHO antinociceptive effect is polymodal, not acting via the HO-1/GMPc/PKG pathway, but depending on the NO and ATP-sensitive K⁺ channels integrity. PHO possesses antinociceptive and anti-inflammatory activities as well as it is not toxic in animals. This product, thus, presents biotechnological relevance in the treatment of orofacial pain.

Orofacial clefts are extremely common birth defects. Orofacial clefts affect a multitude of different areas including feeding, speech, proper tooth development, as well as personality. There are many causes associated with the many different presentations of the birth defect. There have been a multitude of different surgical procedures over time that have dealt with the complications associated with repairing the various clefts. There is no current accepted standard for orofacial cleft repair. In more recent times the focus of the various orofacial clefts procedures have gone from a major procedure where survival was the objective to a more streamline procedure with a man goal of restoring normal human anatomy. Presurgical nasoalveolar molding (PNAM) is more recent procedure that takes advantage of the malleability and rapid growth of facial tissue during the first months of life. This procedure uses a custom acrylic plate that brings the right and left halves of the cleft closer together. This procedure is currently not accepted by all because the long-term effects are unclear. The aim of this study is to point out the short term successes of the PNAM procedure, compare our results to current published studies, and suggest further study that should be completed. A case report was completed on the first five months of treatment on a bilateral cleft lip/ cleft palate case. The case report followed the patient from birth through the first cleft lip closure surgery. The notes taken at weekly appliance adjustment appointments will be reviewed for information on progress as well as behavior and parent involvement. Pictures were also reviewed in order to review progress as well as surgical procedure. After review of the appointment notes and various pictures from throughout the process it was deemed that this PNAM procedure was a success. It was found that there was an overall increase in symmetry in facial structure as well and an increase in facial tissue. After reviewing pictures of the surgical procedure it can be concluded that the overall process was made easier by the PNAM procedure. It is concluded that the PNAM procedure is extremely successful in the short term but in order to receive more concrete results more cases must be reviewed with future follow-ups in order to see consistent long-term results.