Os antibióticos aminoglicosídeos adquiriram uma posição relevante no cenário terapêutico devido ao interesse na regulação da síntese protéica bacteriana em nível de RNA, uma vez que são ligantes inespecíficos para diversos tipos de RNA bacterianos, como RNA mensageiro, RNA transportador e RNA ribossômico. Esta classe de antibióticos apresenta amplo espectro de ação, particularmente contra bactérias Gram-negativas. Recente abordagem estende o uso dos antibióticos aminoglicosídeos como agentes antivirais devido a sua afinidade de ligação ao RRE-, Rev Responsive Element, e TAR-, Trans-Acting Responsive sequence HIV RNA. Por conseguinte, há uma inibição competitiva envolvendo seus correspondentes ligantes naturais, as proteínas Rev e Tat, interrompendo a replicação, do vírus HIV-tipo 1. Em virtude da importância de derivados simplificados dos antibióticos aminoglicosídeos na busca por derivados vestíbulo-tóxico seletivos ou RNA-ligantes, o presente trabalho propõe a síntese do amino- e carba-açúcar 2-desoxiestreptamina, 16, a qual apresenta um desafio sintético interessante devido à presença de cinco centros estereogênicos contínuos com substituintes em relação trans no anel e pode ser utilizada na construção de moléculas mais complexas A estratégia sintética proposta para preparação do composto meso 2-desoxiestreptamina (16), envolve metodologia inédita e foi desenvolvida em duas rotas sintéticas: (i) preparação do carba-açúcar precursor 46 e (ii) preparação de 16 propriamente dito. / Aminoglycoside antibiotics received a relevant position in the therapeutic scenario due to the interest in the regulation of bacterial protein synthesis at the RNA-level, since they are a unspecific ligands to several bacterials RNA types, such as mRNA, tRNA and rRNA. These types of antibiotics show a broad spectrum of activity, particulary against gram negative bacteria. New approach extends the use of aminoglycosides as antiviral agents owing to their binding affinity to RRE- Rev Responsive Element and TAR- Trans-Acting Responsive sequence of HIV RNA. Thus, there is a competitive inhibition involving their corresponding natural ligands Rev and Tat proteins, disrupting the HIV-1 virus replication. Regarding the importance of simplified aminoglycoside antibiotics in the search for selective vestibule-toxic derivatives or RNA-ligands, this work focuses on the synthesis of the amino- and carba-sugar 2-deoxyestreptamine, 16, which has an interesting synthetic challenge related to the presence of five continuous stereogenic centre with substituents in trans disposition in the ring, and may be employed in the construction of more complex molecules. The synthetic strategy proposed to prepare meso 2-deoxyestreptamine (16) involves a new methodology and was performed in two synthetic routes: (i) the synthesis of precursory carba-sugar (46) and (ii) the synthesis of (16) properly.

Σκοπός: Σκοπός της μελέτης ήταν η αξιολόγηση της δυνατότητας πρώιμης διάγνωσης της νόσου Ménière με τη χρήση ηχοκάλυψης χαμηλής συχνότητας. Υλικό και μέθοδος: Τριανταπέντε ασθενείς που έπασχαν από τη νόσο Ménière εξετάστηκαν επανειλημμένα κατά την πορεία της νόσου τους. Τα αποτελέσματα των ασθενών αυτών συγκρίθηκαν με αυτά που ελήφθησαν από 10 αυτιά με φυσιολογική ακοή και 40 αυτιά με βαρηκοΐα από θόρυβο. Οι μετρήσεις πραγματοποιήθηκαν με τη βοήθεια ειδικού εξοπλισμού ικανού να παράγει έναν ήχο χαμηλής συχνότητας σε συνδυασμό με ένα tone burst. Με τη βοήθεια των κατάλληλων μηχανημάτων ήταν δυνατή η ανεξάρτητη μεταβολή του πλάτους των δύο ηχητικών ερεθισμάτων, καθώς και της διαφοράς φάσης μεταξύ τους από 0 ως 360 μοίρες. Προσαρμόζοντας τις εντάσεις και τη διαφορά φάσης ο εξεταζόμενος μπορούσε να ακούσει δύο ήχους έναν χαμηλής συχνότητας ως ηχοκάλυψη και έναν υψηλής συχνότητας που ακουγόταν δυνατότερα από την ηχοκάλυψη. Η κύρια παράμετρος που μελετήθηκε ήταν το πλάτος διαμόρφωσης (modulation depth) που είναι η μέγιστη διαφορά μεταξύ του βέλτιστου και του χείριστου ουδού ακοής ενός εξεταζόμενου στο ακοόγραμμα φάσης και μετράται σε dB HL. Αποτελέσματα:Σε φυσιολογικά άτομα η αποτελεσματικότερη ηχοκάλυψη εντοπίστηκε στις 250° και η μικρότερη στις 360°. Λιγότερο αποτελεσματική ήταν η ηχοκάλυψη που παρατηρήθηκε στις 90°. Τα άτομα με φυσιολογική ακοή είχαν πλάτος διαμόρφωσης (modulation depth) μεταξύ 20 και 35 dB HL, οι ασθενείς με βαρηκοΐα αγωγιμότητας παρουσίασαν modulation depth περίπου 10 dB HL και στους ασθενείς με νόσο Ménière μετρήθηκε πλάτος modulation depth σχεδόν 0 dB. Συμπέρασμα: Ο εξοπλισμός και η μέθοδος που αναπτύξαμε πιθανόν να συμβάλλει στη διάγνωση και διαφορική διάγνωση της νόσου Ménière στα πρώιμα στάδια της και στις εξάρσεις που χαρακτηρίζουν την πορεία της. Ο εξοπλισμός που απαιτείται είναι απλός και προσιτός και μπορεί να βρεθεί σε οποιοδήποτε εργαστήριο ιατρικής φυσικής ή μηχανολογίας. Περισσότερες μελέτες είναι αναγκαίες προκειμένου να διερευνηθεί η πιθανή συμβολή της μελέτης του οπισθίου λαβυρίνθου με ηχοκάλυψη χαμηλής συχνότητας στην πρώιμη διάγνωση της νόσου Ménière. / OBJECTIVES: The evaluation of low frequency masking in early diagnosis of Ménière’s Disease (MD). PATIENTS AND METHODS: Thirty-five patients suffered from Ménière’s disease were examined. The results were compared with that of 10 normal hearing ears and 40 noise damaged ears. The examination of all of these individuals was made by the use of a special instrumentation capable to produce a low frequency sound signal superimposed with a tone burst. We were able to independently change the amplitudes of the two applied signals, as well as the phase lag between them from 0° to 360°. Adjusting the two amplitudes and the phase lag the examined individuals heard two sounds one as the masking tone and one high frequency tone superimposed to that of low frequency masking. RESULTS: In normal individuals the highest masking effect was evident at 250° and the lowest at 360°. A smaller masking effect was also evident at 90°. Normal hearing subjects had a modulation depth between 20 and 35 dB, while patients with noise damaged about 10 dB and patients with Ménière’s disease a modulation depth closing to 0 dB. The instrumentation and method presented in this article, shows a relative good clinical diagnostic accuracy as it is capable to diagnose the basilar membrane stiffness on an almost null modulation depth, and sensitivity near 70%. CONCLUSION: The developed instrumentation and method is possible to distinguish and diagnose the early stages of Ménière’s disease and also the acute recurrences. This may lead to a further study of the results of low frequency masking on the anterior labyrinth from research centers worldwide, in order to reinforce the diagnostic accuracy and strength of this newly developed diagnostic method.

Os antibióticos aminoglicosídeos adquiriram uma posição relevante no cenário terapêutico devido ao interesse na regulação da síntese protéica bacteriana em nível de RNA, uma vez que são ligantes inespecíficos para diversos tipos de RNA bacterianos, como RNA mensageiro, RNA transportador e RNA ribossômico. Esta classe de antibióticos apresenta amplo espectro de ação, particularmente contra bactérias Gram-negativas. Recente abordagem estende o uso dos antibióticos aminoglicosídeos como agentes antivirais devido a sua afinidade de ligação ao RRE-, Rev Responsive Element, e TAR-, Trans-Acting Responsive sequence HIV RNA. Por conseguinte, há uma inibição competitiva envolvendo seus correspondentes ligantes naturais, as proteínas Rev e Tat, interrompendo a replicação, do vírus HIV-tipo 1. Em virtude da importância de derivados simplificados dos antibióticos aminoglicosídeos na busca por derivados vestíbulo-tóxico seletivos ou RNA-ligantes, o presente trabalho propõe a síntese do amino- e carba-açúcar 2-desoxiestreptamina, 16, a qual apresenta um desafio sintético interessante devido à presença de cinco centros estereogênicos contínuos com substituintes em relação trans no anel e pode ser utilizada na construção de moléculas mais complexas A estratégia sintética proposta para preparação do composto meso 2-desoxiestreptamina (16), envolve metodologia inédita e foi desenvolvida em duas rotas sintéticas: (i) preparação do carba-açúcar precursor 46 e (ii) preparação de 16 propriamente dito. / Aminoglycoside antibiotics received a relevant position in the therapeutic scenario due to the interest in the regulation of bacterial protein synthesis at the RNA-level, since they are a unspecific ligands to several bacterials RNA types, such as mRNA, tRNA and rRNA. These types of antibiotics show a broad spectrum of activity, particulary against gram negative bacteria. New approach extends the use of aminoglycosides as antiviral agents owing to their binding affinity to RRE- Rev Responsive Element and TAR- Trans-Acting Responsive sequence of HIV RNA. Thus, there is a competitive inhibition involving their corresponding natural ligands Rev and Tat proteins, disrupting the HIV-1 virus replication. Regarding the importance of simplified aminoglycoside antibiotics in the search for selective vestibule-toxic derivatives or RNA-ligands, this work focuses on the synthesis of the amino- and carba-sugar 2-deoxyestreptamine, 16, which has an interesting synthetic challenge related to the presence of five continuous stereogenic centre with substituents in trans disposition in the ring, and may be employed in the construction of more complex molecules. The synthetic strategy proposed to prepare meso 2-deoxyestreptamine (16) involves a new methodology and was performed in two synthetic routes: (i) the synthesis of precursory carba-sugar (46) and (ii) the synthesis of (16) properly.