Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase.

The antifungal activity of 5-hydroxy-4-oxo-l-norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV-containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI-1640 medium, with minimal inhibitory concentration values in the 32 to 64 µg mL-1 range. This activity was not affected by multidrug resistance that is caused by overexpression of genes encoding drug efflux proteins. The mechanism of antifungal action of HONV dipeptides involved uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. The relative transport rates determined the anticandidal activity of HONV dipeptides.

Transport Deficiency Is the Molecular Basis of Candida albicans Resistance to Antifungal Oligopeptides.

Oligopeptides incorporating N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), an inhibitor of glucosamine-6-phosphate synthase, exhibited growth inhibitory activity against Candida albicans, with minimal inhibitory concentration values in the 0.05-50 µg mL-1 range. Uptake by the peptide permeases was found to be the main factor limiting an anticandidal activity of these compounds. Di- and tripeptide containing FMDP (F2 and F3) were transported by Ptr2p/Ptr22p peptide transporters (PTR) and FMDP-containing hexa-, hepta-, and undecapeptide (F6, F7, and F11) were taken up by the oligopeptide transporters (OPT) oligopeptide permeases, preferably by Opt2p/Opt3p. A phenotypic, apparent resistance of C. albicans to FMDP-oligopeptides transported by OPT permeases was triggered by the environmental factors, whereas resistance to those taken up by the PTR system had a genetic basis. Anticandidal activity of longer FMDP-oligopeptides was strongly diminished in minimal media containing easily assimilated ammonium sulfate or L-glutamine as the nitrogen source, both known to downregulate expression of the OPT genes. All FMDP-oligopeptides tested were more active at lower pH and this effect was slightly more remarkable for peptides F6, F7, and F11, compared to F2 and F3. Formation of isolated colonies was observed inside the growth inhibitory zones induced by F2 and F3 but not inside those induced by F6, F7, and F11. The vast majority (98%) of those colonies did not originate from truly resistant cells. The true resistance of 2% of isolates was due to the impaired transport of di- and to a lower extent, tripeptides. The resistant cells did not exhibit a lower expression of PTR2, PTR22, or OPT1-3 genes, but mutations in the PTR2 gene resulting in T422H, A320S, D119V, and A320S substitutions in the amino acid sequence of Ptr2p were found.

[Glomus caroticum, jugulare and vagale--problems in diagnosis and treatment]. / Przyzwojaki klebka szyjnego, zyly szyjnej wewnetrznej i nerwu blednego--problemy diagnostyczne i lecznicze.

INTRODUCTION: The paraganglia tissue in 80% is located in suprarenal glands. The rest (20%) are with close association with autonomic nerves and some cranial nerves. Paraganglioma, being tumors arising from the paraganglion cells of the parasympathetic system, were first reported in man in 1935. Although histologically these tumors have been shown to contain neurosecretory granules, they are rarely functional. There are four kinds of paragangliomas: deriving from carotid artery baroreceptors (glomus caroticum), internal jugular vein (glomus jugulare); placed along vagal nerve (glomus vagale) and paragangliomas of tympanic cavity (glomus tympanicum). The first three of them are clinically recognized as tumor of the neck. MATERIAL AND METHODS: Authors present group of 7 patients with paragangliomas treated in ENT Department in Poznan in the years 1994-2004. There were treated 4 patients with glomus caroticum, two with glomus vagale and one patient with glomus jugulare. RESULTS: All patients were treated surgically. In one case in group with glomus caroticum in histological examination tendency to infiltration of internal carotid artery was stated (chemodectoma malignum). The tumor was removed totally with partial excision of communis, external and internal carotid artery. The internal carotid artery was closed by the tumor. CONCLUSION: Authors underline three aspects of process of treatment in whole group of patients: diagnostic problems, way of treatment and long term results.

[Evaluation of phonemic hearing development in CI-patients]. / Ocena ksztaltowania sie sluchu fonematycznego w grupie pacjentów zaimplantowanych wszczepem slimakowym.

Phonemic hearing it is a typical interdisciplinary problem. Many specialists like pedagogues, psychologists, phoniatricians and speech therapists are interested in this field. So, we may find many definitions describing this kind of hearing. The speech perception and acquisition of speech is a difficult process profoundly hearing impaired children. With the development of the cochlear implant, acoustic input can be provide to these children. Studies documenting the postoperative performance of children with implants have generally shown significant improvements in speech perception and production. On the opposite side--in the group of postlingually deafened adult the speech rehabilitation is quite short. Only a few specialists described their observation about phonemic hearing development in CI-patients. How do it differ from hearing development in healthy population? The aim of this study was to describe the phonemic hearing development in CI-patients. In the ENT Dept. of University of Medical Sciences in Poznan 280 cochlear implantation were performed. They were observe in three groups: pre-, peri- and postlingually deafened ones. We concluded the same order of phonemic hearing development in every group. The time of acquisition differed, and depended of oral language development before implantation. At first they start to distinct voiced and unvoiced phones, than oral-nasal and sharp-soft ones. The most difficult for them was to discriminate fricative and plosive sounds.

[Cochlear implantation in visually impaired patients--long-term rehabilitation results]. / Wyniki wieloletniej rehabilitacji osób zaimplantowanych wszczepem slimakowym z towarzyszacym uposledzeniem widzenia.

UNLABELLED: The aim of the study was to assess the rehabilitation results in visually impaired patients with cochlear implants. Material consisted of 9 patients (2 with prelingual deafness, 3 with perilingual deafness, 4 with postlingual deafness) from 244 implanted persons in Poznan. METHODS: In all the patients the rehabilitation results were evaluated using Test of Auditory Perception of Speech (TAPS) and screening test. RESULTS: In the group of patients with pre- and perilingual deafness a little bit slower progress of rehabilitation was found, according to 117 persons with prelingual deafness and 34 persons with perilingual deafness without vision disorders. Within the group of patients with postlingual deafness important progress of rehabilitation was observed. Two brothers with Usher syndrome 1-2 months after speech processor switch-on reached the highest level of test, they could communicate with family. One person after 5 months of rehabilitation could talk by phone without any problems. In all implanted visually impaired patients improvement of auditory perception of speech was observed.

[Three kinds of chemodectoma in one patient--a rare case]. / Rzadki przypadek wystapienia trzech rodzajów przyzwojaka u jednej pacjentki.

Tumors arising from paraganglioma tissue are properly called paragangliomas. Preferentially these tumors are named for their site of origin. In the head and neck they are most commonly found arising from the carotid body (glomus caroticum), the jugular bulb (glomus jugulare), the tympanic cavity (glomus tympanicum) and the vagal ganglia (glomus vagale). Mutiple paragangliomas may occur in 2-10%. The purpose of this study was to present the rare case of patient with three kinds of chemodectoma: glomus tympanicum, jugulare i vagale.

[Quality of life in children with cochlear implants and their families (Program Schwarzenberg)--initial report]. / Ocena jakosci zycia u dzieci zaimplantowanych wszczepem slimakowym oraz ich rodzin (Program Schwarzenberg)--doniesienie wstepne.

The aim of the study was to present the results of international evaluation program "Quality of Life in children and their families--Schwarzenberg Initiative". The parents of children under 15 years old was asked to fill out specially prepared questionnaires. 1240 children from 9 countries participated in the study. In Poland 60 families filled out the questionnaires. 80 questions concerned several topics, including reaction of parents to the first information about impaired hearing of their child, using hearing aids before and after implantation, evaluation of behaviour in kindergarten and in school. This initial report describes only a few important topics. In 27.7% of Polish families the impaired hearing of their child was a cause to stop the work of one of the parents, to decrease time of work or to change the place of work in 9.1%. In most of the children the perception of sound was noticed. Only a few families from Austria, Slovenia, Swiss and Italy reported unsatisfactory results after implantation. Implantation increases quality of life of implanted children and their families.

[Changes in interpersonal communication in pre- and perilingually deafened children after cochlear implantation]. / Zmiany sposobu komunikacji interpersonalnej u dzieci z gluchota pre- i perilingwalna po implantacji wszczepem slimakowym.

People with deep prelingual deafness cannot fluently use oral language as a basic mode of communication. Hearing impaired subjects elaborated their own mode of communication. Cochlear implants as a surgical mode of deafness treatment may create a new chance for prelingually deaf children to develop vocal speech. The aim of this study was to assess changes in interpersonal mode of communication in pre- and perilingually deaf children after cochlear implantation. It was observed, that cochlear implantation stimulates development of oral language. The possibility of hearing perception of oral language it is a chance for a child for fully participation in life of hearing societies.

[Poznan's program of cochlear implantation: 10 years experience]. / Poznanski Program Leczenia Gluchoty Metoda Wszczepów Slimakowych--10 lat doswiadczen.

The first cochlear implant in the ENT Department in Poznan was introduced in adult patient in January 1994. One year later the first deaf child was implanted. During 10 years over 200 deaf people were operated on. Modifications of diagnostics, surgery and rehabilitation were presented. Lowering the age of the implantation, changes of audiological criteria, genetic diagnostic and possibility of implantation in multi-handicapped patients were emphasized. Almost all surgeries were performed through the posterior tympanotomy and in one cases through the middle fossa approach. In one child with total ossification in CT scans Nucleus Double Array was used. Speech rehabilitation bases on auditory-verbal therapy. Rehabilitation consists of individual sessions with speech therapist and group therapy. Logorytmics exercises were introduced.

[Usefulness of TAPS (Polish version) for evaluation of CI children's progress in speech rehabilitation--7 years of observation]. / Przydatnosc polskiej wersji testu TAPS do oceny postepów rehabilitacji mowy dzieci z implantem slimakowym--obserwacje 7-letnie.

The speech rehabilitation of pre- and perilingually deafened children with cochlear implants it is a very long process. It should be individualized for needs of every young patient. It is possible only after correct evaluation of speech level. There are many tests for this evaluation. Among them same are more known like TAPS test. Test of Auditory Perception of Speech (TAPS) was elaborated in English at Basel University in Swiss. It was translated to Polish at Adam Mickiewicz University and Karol Marcinkowski University School of Medical Sciences in Poznan. The authors present their own 7-years observations.

[Distinctness and discrimination of phonemes in children with cochlear implants--preliminary report]. / Wyrazistosc i zrozumialosc glosek u dzieci poslugujacych sie wszczepem slimakowym--doniesienie wstepne.

There are many tests prepared for speech evaluation for different age groups and with any disabilities. The percent of correct repeated mono- or bisyllabes words create the final result. Sometimes this score is lower than real oral communication skill of CI patient. In the years 1994-2002 in Poznan 158 cochlear implantations were performed. Since few months the evaluation of the distinctness and discrimination of phonems of cochlear implants children are being conducted. It was found some differences between distinctness and discrimination of phonems and discrimination of words. It means that scores achieved by children in standarized words--tests do not reflect the real level of speech development of each child.

[Changes in reaction on stress situations in children after cochlear implantation]. / Zmiana sposobu reakcji na sytuacje frustracji u dzieci nieslyszacych po zastosowaniu wszczepu slimakowego.

Hearing impaired child has no chance to receive any sounds informations about his/her environment. It is strictly connected to speech development inhibition. It reflects on thinking process and disturbs social and emotional development of hearing impaired child. It also creates isolation from hearing environment. Cochlear implants improve hearing and may improve contacts with hearings environment through its better understanding. These devices may also change reaction on stress situations. The aim of this paper was assessmant of this changes before and after implantation. In our group majority of children after implantation feel able to overcome any difficulties during contacts with hearing environment. This makes speech rehabilitation easier as well.

[Glomus vagale tumor--diagnosis and treatment]. / Glomus vagale--diagnostyka i leczenie.

Paraganglioma, being tumors arising from the paraganglion cells of the parasympathetic system, were first reported in man in 1935. Within, the head and neck glomus vagale tumors account for less than 5% of all paragangliomas, with approximately 10% being multicentric. Although histologically these tumors have been shown to contain neurosecretory granules, they are rarely functional. Vagal chemodectomas are histologically benign, but are one of the most difficult tumors of the skull base to manage. Authors present a case of 56 years old woman with glomus vagale tumor treated in ENT Dept. in Poznan.

[Nonchromaffinic paraganglioma (chemodectoma) of tympanic cavity]. / Przyzwojak niechromochlonny (chemodectoma) jamy bebenkowej.

Nonchromaffinic paraganglioma derives from neuroectoderma. It is characterised by plenty vascularisation. Histopathologically it is a benign tumor, and doesn't give any metastasis. Although because of localisation, vascularisation and possibility of bone destruction is clinically malignant. In this paper we present three cases of paraganglioma localised in tympanic cavity treated surgically.