X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney

Audiologic evaluation of newborns and infants admitted in intensive care unit and intermediary care

Introdução: A prevalência de perda auditiva em recém-nascidos (RN) normais e lactentes é estimada em 1,5 a 6/1.000 nascidos vivos, sendo que naqueles considerados de alto risco varia de 1,5 a 17%. Objetivos: Verificar a prevalência de deficiência auditiva adquirida em RN e lactentes que ficaram internados em unidade de cuidados intensivos (UTI) e intermediários; relacionar a deficiência auditiva com a existência de fatores de risco para este evento e determinar o nível anatômico da lesão nos RN que apresentarem esta deficiência. Métodos: Estudo de coorte prospectivo no período de setembro de 2003 a março de 2004, com 71 recém-nascidos de três Hospitais da cidade de São Paulo, com populações de características semelhantes. Em relação ao sexo, 26 (36,62%) eram do sexo feminino e 45 (63,38%) do masculino; a média de peso e idade gestacional ao nascimento foi 2.480,63g (825g-4215g) e 36,14 semanas (25,57 - 41,57 semanas), respectivamente. Os 71 RN realizaram a primeira avaliação auditiva utilizando o método de emissão otoacústica evocada transiente (EOAET) aplicado durante a internação hospitalar. A segunda avaliação foi ambulatorial e além de o método de EOAET foi aplicado também o de audiometria de tronco cerebral (ABR). A média de idade cronológica e idade gestacional corrigida na primeira avaliação auditiva foi 19,36 dias e 38,86 semanas, enquanto na segunda avaliação foi 73,50 dias e 46,61 semanas, respectivamente. Os fatores de risco escolhidos para testar uma possível relação com deficiência auditiva foram: perinatais, respiratórios, infecciosos, metabólicos, uso de equipamentos e outros, como: tempo de ventilação mecânica, utilização de oxigenioterapia não invasiva, tempo de incubadora e tempo de internação na UTI, fármacos ototóxicos, neurológicos, insuficiência renal e retinopatia da prematuridade. Os dados foram avaliados descritivamente pelo cálculo de médias e proporções, análise inferencial e teste de concordância entre a primeira e segunda avaliação audiológica. Resultados: Dos 71 RN avaliados, 23 (32,39%) apresentaram alteração auditiva, sendo 8 (30,77%) do sexo feminino e 15 (33,33%) do masculino. Em relação à lateralidade, 11 (47,83%) RN apresentaram alterações unilaterais e 12 (52,17%) bilaterais e em relação ao local da lesão, 14 (60,87%) apresentaram alterações cocleares, 1 (4,35%) retrococlear e 8 (34,78%) mista. A alteração auditiva esteve estatisticamente associada com: RN pequeno para a idade gestacional, apnéia, hipocalcemia, uso de dois ou mais fármacos ototóxicos, amicacina e furosemida Houve fraca concordância entre as duas avaliações realizadas com EOAET (k=0,138, intervalo de confiança (95%)=[0; 0,364]). Conclusões: a prevalência de perda auditiva nos RN e lactentes internados nas unidades de cuidados intensivos e intermediários foi mais elevada do que a da citada na literatura. Houve associação estatística com seis fatores de risco estudados e não houve diferença entre o comprometimento unilateral e bilateral, com predomínio da freqüência de alterações cocleares, seguidas de alterações mistas e retrococlearesIntrodution: The prevalence of newborn and infant hearing loss is estimated to range 1.5 to 6 per 1.000 live births and newborn with risk factors for hearing loss range 1.5 to 17%. Objective: To verify the prevalence of newborns and infants hearing loss admitted in the intensive and intermediary care unit; to relate the hearing loss with the presence of risk factors for such event and to determine the wound anatomic level. Methods: It is a prospective cohort study with 71 newborns (NB), in three Hospitals in São Paulo (September 2003 and March 2004). Twenty six (36.62%) NB females and 45 (63.38%) males. The average of the weight and of the gestational age at the birth were 2,480.63 g (825 g-4,215 g) and 36.14 weeks (25.57-41.57 weeks), respectively. The first evaluation using the transient evoked otoacoustic emission during the hospitalization. The second was performed in the ambulatory of the hospital with transient evoked otoacoustic emission and auditory brainstem response. The average of the chronologic age and of the gestacional age at the first evaluation were 19.36 days and 38.86 weeks and at the second evaluation were 73.50 days and 46.61 weeks, respectively. The risk factors for hearing loss evaluated: perinatal, respiratory, infection, metabolic, use of equipment and others (mechanical ventilation duration, use of non-invasive oxygen-therapy, time in the incubator and neonatal in the intensive unit care), ototoxic medications, neurological, renal ins ufficiency and retinopathy of prematurity. The data were evaluated calculating averages and proportions, inferential analysis and concordance test between the first and the second audiologic evaluation. Results: Twenty three (32.39%) NB of the 71 presented a hearing loss, eight (30.77%) females and 15 (33.33%) males. Eleven (47.83%) newborns presented unilateral alteration and 12 (52.17%) bilateral. Fourteen NB (60.87%) presented cochlear alteration, 1 (4.35%) retrocochlear and 8 (34.78%) mixed. The hearing loss was significantly associated with small for gestational age newborns; apnea, hypocalcaemia, administration ototoxic medications, administration of amicacine and furosemida. The concordance test between the first and the second transient evoked otoacoustic emission was weak (k=0.138, 95%confidence interval 0;0.364). Conclusions: The prevalence of hearing loss in this study was high that in the literature. The hearing loss was significantly associated with six risks factors studied. The difference between unilateral and bilateral alteration wasn\'t observed, the cochlear alteration was more frequent, following the mixed and retrocochlear alteratio

Audiologic evaluation of newborns and infants admitted in intensive care unit and intermediary care

Introdução: A prevalência de perda auditiva em recém-nascidos (RN) normais e lactentes é estimada em 1,5 a 6/1.000 nascidos vivos, sendo que naqueles considerados de alto risco varia de 1,5 a 17%. Objetivos: Verificar a prevalência de deficiência auditiva adquirida em RN e lactentes que ficaram internados em unidade de cuidados intensivos (UTI) e intermediários; relacionar a deficiência auditiva com a existência de fatores de risco para este evento e determinar o nível anatômico da lesão nos RN que apresentarem esta deficiência. Métodos: Estudo de coorte prospectivo no período de setembro de 2003 a março de 2004, com 71 recém-nascidos de três Hospitais da cidade de São Paulo, com populações de características semelhantes. Em relação ao sexo, 26 (36,62%) eram do sexo feminino e 45 (63,38%) do masculino; a média de peso e idade gestacional ao nascimento foi 2.480,63g (825g-4215g) e 36,14 semanas (25,57 - 41,57 semanas), respectivamente. Os 71 RN realizaram a primeira avaliação auditiva utilizando o método de emissão otoacústica evocada transiente (EOAET) aplicado durante a internação hospitalar. A segunda avaliação foi ambulatorial e além de o método de EOAET foi aplicado também o de audiometria de tronco cerebral (ABR). A média de idade cronológica e idade gestacional corrigida na primeira avaliação auditiva foi 19,36 dias e 38,86 semanas, enquanto na segunda avaliação foi 73,50 dias e 46,61 semanas, respectivamente. Os fatores de risco escolhidos para testar uma possível relação com deficiência auditiva foram: perinatais, respiratórios, infecciosos, metabólicos, uso de equipamentos e outros, como: tempo de ventilação mecânica, utilização de oxigenioterapia não invasiva, tempo de incubadora e tempo de internação na UTI, fármacos ototóxicos, neurológicos, insuficiência renal e retinopatia da prematuridade. Os dados foram avaliados descritivamente pelo cálculo de médias e proporções, análise inferencial e teste de concordância entre a primeira e segunda avaliação audiológica. Resultados: Dos 71 RN avaliados, 23 (32,39%) apresentaram alteração auditiva, sendo 8 (30,77%) do sexo feminino e 15 (33,33%) do masculino. Em relação à lateralidade, 11 (47,83%) RN apresentaram alterações unilaterais e 12 (52,17%) bilaterais e em relação ao local da lesão, 14 (60,87%) apresentaram alterações cocleares, 1 (4,35%) retrococlear e 8 (34,78%) mista. A alteração auditiva esteve estatisticamente associada com: RN pequeno para a idade gestacional, apnéia, hipocalcemia, uso de dois ou mais fármacos ototóxicos, amicacina e furosemida Houve fraca concordância entre as duas avaliações realizadas com EOAET (k=0,138, intervalo de confiança (95%)=[0; 0,364]). Conclusões: a prevalência de perda auditiva nos RN e lactentes internados nas unidades de cuidados intensivos e intermediários foi mais elevada do que a da citada na literatura. Houve associação estatística com seis fatores de risco estudados e não houve diferença entre o comprometimento unilateral e bilateral, com predomínio da freqüência de alterações cocleares, seguidas de alterações mistas e retrococlearesIntrodution: The prevalence of newborn and infant hearing loss is estimated to range 1.5 to 6 per 1.000 live births and newborn with risk factors for hearing loss range 1.5 to 17%. Objective: To verify the prevalence of newborns and infants hearing loss admitted in the intensive and intermediary care unit; to relate the hearing loss with the presence of risk factors for such event and to determine the wound anatomic level. Methods: It is a prospective cohort study with 71 newborns (NB), in three Hospitals in São Paulo (September 2003 and March 2004). Twenty six (36.62%) NB females and 45 (63.38%) males. The average of the weight and of the gestational age at the birth were 2,480.63 g (825 g-4,215 g) and 36.14 weeks (25.57-41.57 weeks), respectively. The first evaluation using the transient evoked otoacoustic emission during the hospitalization. The second was performed in the ambulatory of the hospital with transient evoked otoacoustic emission and auditory brainstem response. The average of the chronologic age and of the gestacional age at the first evaluation were 19.36 days and 38.86 weeks and at the second evaluation were 73.50 days and 46.61 weeks, respectively. The risk factors for hearing loss evaluated: perinatal, respiratory, infection, metabolic, use of equipment and others (mechanical ventilation duration, use of non-invasive oxygen-therapy, time in the incubator and neonatal in the intensive unit care), ototoxic medications, neurological, renal ins ufficiency and retinopathy of prematurity. The data were evaluated calculating averages and proportions, inferential analysis and concordance test between the first and the second audiologic evaluation. Results: Twenty three (32.39%) NB of the 71 presented a hearing loss, eight (30.77%) females and 15 (33.33%) males. Eleven (47.83%) newborns presented unilateral alteration and 12 (52.17%) bilateral. Fourteen NB (60.87%) presented cochlear alteration, 1 (4.35%) retrocochlear and 8 (34.78%) mixed. The hearing loss was significantly associated with small for gestational age newborns; apnea, hypocalcaemia, administration ototoxic medications, administration of amicacine and furosemida. The concordance test between the first and the second transient evoked otoacoustic emission was weak (k=0.138, 95%confidence interval 0;0.364). Conclusions: The prevalence of hearing loss in this study was high that in the literature. The hearing loss was significantly associated with six risks factors studied. The difference between unilateral and bilateral alteration wasn\'t observed, the cochlear alteration was more frequent, following the mixed and retrocochlear alteratio

Effects of iodinated contrast media in a novel model for cerebral vasospasm

Objective We developed an in vitro model for vasospasm post subarachnoid hemorrhage that was suitable for investigating brain vessel autoregulation. We further investigated the effects of iodinated contrast medium on the vascular tone and the myogenic response of spastic cerebral vessels. Method We isolated and perfused the superior cerebellar arteries of rats. The vessels were pressurized and studied under isobaric conditions. Coagulated blood was used to simulate subarachnoid hemorrhage. The contrast medium iodixanol was applied intraluminally. Results Vessels exposed to blood developed significantly stronger myogenic tone (65.7 ± 2.0% vs 77.1 ± 1.2% of the maximum diameter, for the blood and the control group, respectively) and significantly decreased myogenic response, compared with the control groups. The contrast medium did not worsen the myogenic tone or the myogenic response in any group. Conclusion Our results show that deranged myogenic response may contribute to cerebral blood flow disturbances subsequent to subarachnoid hemorrhage. The contrast medium did not have any negative influence on vessel tone or myogenic response in this experimental setting

Functional Epigenetic Analysis of Prostate Carcinoma: A Role for Seryl-tRNA Synthetase?

Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to reexpress transcriptional silenced genes may identify such inactivated genes for needing further evaluation. We aimed to identify genes so far not known to be inactivated by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were treated with the DNMT inhibitor zebularine. Expression changes of total RNA from treated and untreated cells were compared using an RNA expression microarray. Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of paired normal and tumor tissues of prostate cancer patients. SARS was found to be downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold standard for promoter hypermethylation-inactivated genes in prostate cancer (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive Spearman correlations were found between these genes. SARS was discovered to be a novel gene that is repressed in prostate cancer and could therefore be recommended for its involvement in prostate carcinogenesis