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Biomedical subjects

Alessandro Martini

Publications and source records attributed to Alessandro Martini.

At least 19 recordsLinked to original sources

Goldenhar syndrome in association with agenesia of the internal carotid artery.

The association between Goldenhar syndrome and homolateral internal carotid artery agenesis to our knowledge, has never emerged before. We present a case report in a female child that was examined with tonal audiometry, A.B.R., CT scan, MR, digital-subtraction-angiography and color Doppler. The aim of this report is to present an uncommon pathologic association which also provides a brief review of the embryology of the ear and carotid vessels whilst discussing probable pathogenetic causes.

Angiography, Digital Subtraction↗

Merkel cell tumour of the external ear. Report of a case.

Merkel cells carcinoma (MCC) is an uncommon skin lesion, considered a malignancy of the neuroendocrine system, which is found mainly in elderly people. Its incidence is highly correlated with sun exposure or immunodeficiency syndromes. MCC is often an aggressive tumour with high tendency for local recurrence, lymph node involvement and distant metastasis. To our best knowledge 20 cases originated from the auricle have been described, 2 of them arising from external ear canal. The authors report a case of the ear canal characterized by two others synchronous tumours and the occurrence of a malignant high grade lymphoma, in which contribute of the pathologist was essential for a critical review. MCC diagnosis is not always easy for its pathological and clinical features and it should always be considered in presence of lymphoma. A multidisciplinary approach is basic.

Aged↗

Tissue engineering and cartilage regeneration for auricular reconstruction.

OBJECTIVE: This paper will provide (a) a review on current status of auricular reconstruction (b) particularly focusing on the current data about pinna reconstruction using stem cells in combination with tissue engineering. METHODS: The paper is divided into two sections. The first section presents a brief overview of the current status of auricular reconstruction. In the second section, the authors review the aspects and the current status of stem cells and tissue engineering researches related to cartilage regeneration. CONCLUSIONS: Total auricular reconstruction represents one of the greatest challenges for the ENT and Facial Plastic surgeon. The matter of auricular cartilage reconstruction is complex, and progresses in material designs as well as in stem cells field are essential. Even if this bio-technology field is promising, the progresses still are not adequate as patient expectations remain high.

Bioartificial Organs↗

Cisplatin-induced apoptosis in human promyelocytic leukemia cells.

Cis-diamminedichloroplatinum (II) cisplatin (CDDP) is an organometallic compound frequently used in anti-cancer therapy, in particular ovarian, testicular, and head and neck tumors. We found cisplatin was effective against human promyelocytic leukemia cell line HL-60, inhibiting cell cycle progression and inducing time- and concentration- dependent cell death. Presence of nuclear fragmentation, caspase-3 cleavage and annexin V positivity suggests cell death occurred by apoptosis, although DNA internucleosomal fragmentation was not detected. In addition, analysis of malondialdehyde (MDA) production and protein carbonylation indicated that cisplatin increased lipid peroxidation and oxidation of cell proteins. This occurrence was prevented by antioxidants such as N-acetylcysteine (N-aC) and glutathione (GSH), which, consistently, were also able to prevent CDDP-induced cell death. Collectively, these findings indicate that, besides growth inhibition, an increase of oxygen radicals and lipid degradation can account for a significant part of CDDP-induced apoptosis.

Apoptosis↗

Production of volatile organic compounds (VOCs) by yeasts isolated from the ascocarps of black (Tuber melanosporum Vitt.) and white (Tuber magnatum Pico) truffles.

Twenty-nine yeast strains were isolated from the ascocarps of black and white truffles (Tuber melanosporum Vitt. and Tuber magnatum Pico, respectively), and identified using a polyphasic approach. According to the conventional taxonomic methods, MSP-PCR fingerprinting and sequencing of the D1/D2 domain of 26S rDNA, the strains were identified as Candida saitoana, Debaryomyces hansenii, Cryptococcus sp., Rhodotorula mucilaginosa, and Trichosporon moniliiforme. All isolates assimilated L: -methionine as a sole nitrogen source and produced the volatile organic compounds (VOCs), 2-methyl butanol, 3-methyl butanol, methanethiol, S-methyl thioacetate, dimethyl sulfide, dimethyl disulfide, dimethyl trisulfide, dihydro-2-methyl-3(2H)-thiophenone and 3-(methylthio)-1-propanol (MTP). ANOVA analysis of data showed significant (P<0.01) differences in VOCs produced by different yeasts, with MTP as the major component (produced at concentrations ranging from 19.8 to 225.6 mg/l). In addition, since some molecules produced by the isolates of this study are also characteristic of truffle complex aroma, it is possible to hypothesize a complementary role of yeasts associated with this ecosystem in contributing to final Tuber spp. aroma through the independent synthesis of yeast-specific volatile constituents.

Ascomycota↗

GJB2 mutations and degree of hearing loss: a multicenter study.

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.

Adolescent↗

Characterization of the in vitro antimycotic activity of a novel killer protein from Williopsis saturnus DBVPG 4561 against emerging pathogenic yeasts.

A novel killer toxin, labelled as KT4561, secreted by Williopsis saturnus DBVPG 4561, was found to possess a wide antimycotic activity against strains of Candida glabrata, Issatchenkia orientalis and Pichia guillermondii. KT4561 was precipitated by ethanol and purified by ion-exchange chromatography. The active protein migrated as a single band in SDS-PAGE and was characterized by a molecular weight of approximately 62 kDa. Purified KT4561 was active across wide ranges of temperature (5-45 degrees C) and pH (4.5-8.0) and displayed a rapid decrease in viability of yeast cells after 4-8 h. The in vitro activity of KT4561 against 102 yeast isolates (79% of clinical origin) was determined: MIC(50) and MIC(90) of strains were 0.08 and 0.15 microg/ml for C. glabrata, 0.03 and 0.23 microg/ml for I. orientalis and 1.50 and 2.25 microg/ml for P. guilliermondii. Comparative susceptibility tests showed that a high number of strains used in the present study were insensitive to selected azole and polyene antibiotics. The present study demonstrated the potential of KT4561 to be applied as novel control agent against pathogenic yeasts.

Antifungal Agents↗

RNA expression induced by cisplatin in an organ of Corti-derived immortalized cell line.

Cisplatin [cis-diamminedichloroplatinum(II)] (CDDP) is an organic compound that is widely used for the treatment of a large number of tumors. Its clinical use is limited by the presence of some undesired side effects, like as oto- and nephro toxicity, whose mechanisms of action are not understood. One of the possible CDDP toxicity mechanism seems to involve the generation of reactive oxygen species (ROS), that can impair morphology and function of hair cells (HC) in the organ of Corti. To test this hypothesis we evaluated the effect of CDDP treatment on RNA steady-state levels of 15,000 genes by microarray analysis, using, as a experimental model, the OC-k3 cell line, obtained from the organ of Corti of transgenic mice and constitutively expressing the large SV40 T antigen. We have found overexpression of several genes related to arachidonate mobilization including phospholipase A2, group IV and V, phospholipase A2 activating protein and lysophospholipase I and III, as well as lipoxygenation like arachidonate 12-lipoxygenase and arachidonate 5-lipoxygenase activating protein. In addition, we found significant transcription of genes regulating cell respiration, including cyt c oxidase, as well as genes involved in xenobiotic detoxification and lipid peroxidation such as cyt P450, and other oxidases including spermine oxidase and monoamine oxidase. As a whole, overexpression of the group of different genes seems to indicate that an oxidative burst could take place during cisplatin administration. We therefore searched for evidences of superoxide anion and hydrogen peroxide by means of electron paramagnetic resonance (EPR) spectroscopy and flow cytometry, but failed to detect them. On the other hand, we found an increase of malondialdehyde (MDA) synthesis and protein carbonylation products, indicating the occurence of lipid peroxidative degradation. When we tested the effectiveness of butylated hydroxytoluene (BHT), dithiothreitol (DTT) and N-acetylcysteine (N-Ac) as cytoprotectants, all of them reduced protein carbonylation to control levels and significantly protected OC-k3 from CDDP-induced cell death, with an higher protection when using the lipophylic antioxidant BHT. The same antioxidants prevented also the onset of protein carbonylation, which extent was decreased to basal levels. These data indicate that CDDP is able to stimulate gene expression up to 12 h after the beginning of the treatment. This increase in gene transcription involves a large number of genes potentially able to increase the level of cell ROS. Consistently, cells survival is improved by cotreatment with antioxidants, in particular lipophilics.

Acetylcysteine↗

Contribution of winery-resident Saccharomyces cerevisiae strains to spontaneous grape must fermentation.

The origin of the Saccharomyces cerevisiae strains that are responsible for spontaneous grape must fermentation was investigated in a long-established industrial winery by means of two different approaches. First, seven selected components of the analytical profiles of the wines produced by 58 strains of S. cerevisiae isolated from different sites and phases of the production cycle of a Grechetto wine were subjected to Principal Components Analysis. Secondly, the same S. cerevisiae isolates underwent PCR fingerprinting by means of delta primers. The results obtained by both methods demonstrate unequivocally that under real vinification conditions, the S. cerevisiae strains colonising the winery surfaces are the ones that carry out the natural must fermentation.

Base Sequence↗

Otoacoustic emissions at different click intensities: invariant and subject-dependent features.

A study of click-evoked otoacoustic emissions (CEOAEs) elicited at stimulation intensities from 35 to >80 dB was carried out by recurrence quantification analysis on signals from both normal and hearing-impaired subjects. In normal subjects, a clear scaling of determinism with increasing stimulation intensity was observed in the click intensity range from 41 to 59 dB. Outside that range and, in particular, above its upper end, subject-dependent features appeared in the form of different maximal levels of determinism. A comparative analysis of responses from hearing-impaired subjects with conductive hearing losses and sensorineural hearing losses suggested that the principal contributor to this behavior is the middle ear and allowed us to discriminate the two pathologies solely on the basis of CEOAEs. These observations are consistent with a simple phenomenological model of the auditory periphery in which different functional modules are sequentially recruited at increasing stimulus intensities, with a consequent rise in CEOAE coherence.

Acoustic Stimulation↗

Biotechnology of natural and winery-associated strains of Saccharomyces cerevisiae.

A new body of evidence challenges the original consolidated theory of Pasteur on the natural (vineyard) origin of wine strains of Saccharomyces cerevisiae and instead indicates a local, winery-restricted life cycle. The findings open novel biotechnological perspectives for obtaining autochthonous selected starters for the wine industry. A local, individual, and specific fermenting yeast flora, mass selected year after year through many generations of S. cerevisiae in grape must, is present on the surfaces of every winery. These yeast strains are endowed with exceptional enological properties and capable of producing an assortment of volatile compounds apparently contributing to the specific bouquet of locally produced wines.

Biotechnology↗

Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin.

Carboplatin is a second generation platinum-containing anti-tumor drug which selectively alters the micromechanical function of the inner hair cells (IHCs) of the organ of Corti in the chinchilla. Data from a recent study [Wake et al., Acta Otolaryngol. 116 (1996) 374-381], using the chinchilla model, have suggested that a moderate dose of carboplatin alters the efferent feedback loop gain of the OHCs. The present study was designed to evaluate the possible 'efferent feedback alteration mechanism' in the Sprague-Dawley rat using distortion product otoacoustic emissions (DPOAEs). A moderate dose of carboplatin (50 mg/kg body weight) was administered by a 30 min i.p. infusion. Pre- and 72-h post-treatment DPOAE and auditory brainstem response (ABR) recordings were acquired from a group of 12 rats. The animals were anesthetized with a ketamine-atropin anesthesia administered in two consecutive phases. The DPOAE responses (cubic distortion products) were recorded with four asymmetrical protocols: P1=60-50, P2=50-40, P3=40-30 and P4=30-20 dB SPL (sound pressure level), in the frequency range from 4.0 to 16 kHz. ABR responses were obtained for bipolar clicks and tone pips at the frequencies 8.0, 10.0, 20.0 and 30 kHz using stimuli in the range from 100 to 30 dB SPL. Significant ABR threshold shifts of 15 dB were observed at 30 kHz, and shifts of 10 dB at 20, 16 and 10 kHz. The comparison of pre- and post-treatment DPOAE responses did not reveal any significant changes for protocols P1, P2 and P4. Data from the P3 protocol indicated a decrease of the DPOAE amplitude. The findings from the rat model suggest that (a) moderate doses of carboplatin do not affect the efferent feedback loop OHC function and (b) the cochlear susceptibility to carboplatin across species is different, even at moderate-dose regimes.

Animals↗

A study on volatile organic compounds (VOCs) produced by tropical ascomycetous yeasts.

As a part of a program aiming at the selection of strains which might be of interest as sources of natural flavouring molecules, the production of volatile organic compounds (VOCs) by 98 ascomycetous yeast strains (representative of 40 species belonging to 12 genera) isolated from tropical environments was investigated. Volatiles produced were sampled by means of headspace solid-phase microextraction (SPME) and the compounds were analysed and identified by gas chromatography-mass spectroscopy (GC-MS). The VOCs produced were found to be alcohols (amyl alcohol and isoamyl alcohol), aldehydes (2-methyl-2-hexenal and 2-isopropyl-5-methyl-2-hexenal) and esters (ethyl isobutyrate, isobutyl acetate, isoamyl acetate, 2-methylbutyl acetate, ethyl isovalerate, isoamyl propionate and phenylmethyl acetate). Differences in VOC profiles were used to cluster the yeast strains into 25 VOC phenotypes. The different frequency of VOC phenotypes in three specific habitats was correlated to the divergent environmental conditions, possibly affecting the selection of specific yeasts. From a biotechnological viewpoint, this study reveals the potentiality of ascomycetous yeasts isolated from tropical environments as a promising source of VOCs relevant in food and fragrance industry.

Alcohols↗

Progress in understanding GJB2-linked deafness.

Mutations in the GJB2 gene (encoding for Connexin 26 protein) represent a leading cause of genetic hearing impairment. Extensive epidemiological and molecular studies have been reported, describing GJB2 mutations type, frequency and distribution. Moreover, several aspects of GJB2 mutations pathogenic effects have been elucidated taking advantage of in vitro and in vivo experimental approaches. Progress through reported studies is reviewed, highlighting recent major achievements in this field. Attention is focused on different unresolved questions regarding GJB2 deafness pathogenesis and genotype-phenotype relationships. Clarification of these important clues will significantly increase our understanding of the molecular basis of hearing loss and will improve the effectiveness of diagnosis and counselling of this frequent disease.

Connexin 26↗

Evaluation of anesthesia effects in a rat animal model using otoacoustic emission protocols.

Anesthesia effects on otoacoustic emission (OAE) recordings were evaluated in a group of 72 Sprague-Dawley rats (mean weight 225+/-20 gr). Two anesthesia dosages (high and normal) and two anesthetic protocols (ketamine-xylazine, ketamine-xylazine-atropine) were tested. Transient evoked OAE (TEOAE) and distortion product OAE (DPOAE) responses were recorded in 10 min intervals, for a total period of 60 min. Analyses of the data with repeated measure models indicated the following: (1) The animals receiving a high dose of anesthesia (cumulative dose 66.6 mg of ketamine and 13.2 mg of xylazine/kg of body weight) presented significant alterations of the TEOAE response level and the signal to noise ratio at 3.0 kHz; (2) the animals receiving a normal dose of ketamine-xylazine anesthesia (cumulative dose 50 mg of ketamine and 10 mg of xylazine/kg of body weight) presented TEOAE and DPOAE responses invariant in terms of time; (3) significant differences were observed in the DPOAE responses from animals anesthetized with ketamine-xylazine and ketamine-xylazine-atropine. The data support the hypothesis that the ketamine anesthesia OAE suppressing mechanism is related to middle-ear mechanics.

Adjuvants, Anesthesia↗

Ototoxic effects of cisplatin in a Sprague-Dawley rat animal model as revealed by ABR and transiently evoked otoacoustic emission measurements.

The ototoxic effects of cisplatin in a Sprague-Dawley rat model were evaluated by recordings of auditory brainstem responses (ABR) and transiently evoked otoacoustic emissions (TEOAEs). The ABR responses were evoked from alternating clicks and 8, 10, 12, 16, 20 and 30 kHz tone pips in a range from 40 to 100 dB SPL range. The TEOAEs were recorded with a non-linear protocol, and were evoked by a 63.5 dB SPL click stimulus. Twenty five male Sprague-Dawley rats were used in the study, 20 animals were treated with cisplatin (16 mg/kg, body weight) and five animals served as controls. The data showed that 72 h after the cisplatin administration, the TEOAE and ABR variables were significantly altered. The relationship between the ABR and TEOAE variables was shown to be non-linear. The most significant relationships were observed between the TEOAE correlation and the ABR threshold values at 10, 12, and 16 kHz.

Acoustic Stimulation↗