Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss

The inner ear was previously assumed to be an immune-privileged organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets

Expression of Cyclins A, E and Topoisomerase II α correlates with centrosome amplification and genomic instability and influences the reliability of cytometric S-phase determination

BACKGROUND: The progression of normal cells through the cell cycle is meticulously regulated by checkpoints guaranteeing the exact replication of the genome during S-phase and its equal division at mitosis. A prerequisite for this achievement is synchronized DNA-replication and centrosome duplication. In this context the expression of cyclins A and E has been shown to play a principal role. RESULTS: Our results demonstrated a correlation between centrosome amplification, cell cycle fidelity and the level of mRNA and protein expression of cyclins A and E during the part of the cell cycle defined as G1-phase by means of DNA content based histogram analysis. It is shown that the normal diploid breast cell line HTB-125, the genomically relatively stable aneuploid breast cancer cell line MCF-7, and the genomically unstable aneuploid breast cancer cell line MDA-231 differ remarkably concerning both mRNA and protein expression of the two cyclins during G1-phase. In MDA-231 cells the expression of e.g. cyclin A mRNA was found to be ten times higher than in MCF-7 cells and about 500 times higher than in HTB-125 cells. Topoisomerase II α showed high mRNA expression in MDA compared to MCF-7 cells, but the difference in protein expression was small. Furthermore, we measured centrosome aberrations in 8.4% of the MDA-231 cells, and in only 1.3% of the more stable aneuploid cell line MCF-7. MDA cells showed 27% more incorporation of BrdU than reflected by S-phase determination with flow cytometric DNA content analysis, whereas these values were found to be of the same size in both HTB-125 and MCF-7 cells. CONCLUSIONS: Our data indicate that the breast cancer cell lines MCF-7 and MDA-231, although both DNA-aneuploid, differ significantly regarding the degree of cell cycle disturbance and centrosome aberrations, which partly could explain the different genomic stability of the two cell lines. The results also question the reliability of cytometric DNA content based S-phase determination in genomically unstable tumor cell populations

Gluteal-fold adipofascial perforator flap transposition for rectourethral fistula reconstruction

If a rectourinary fistula does not close spontaneously, it requires surgical closure. We present our experience of rectourethral fistula reconstruction using a gluteal-fold perforator flap, resulting in a successful outcome. The patient was a 64-year-old man with prostate cancer who underwent radical prostatectomy. However, he developed rectourinary fistula, which required surgical closure. A dissection was undertaken to divide the fistula tract, and the rectal and urethral defect were closed. A 12.0×3.0 cm gluteal-fold adipofascial perforator flap was harvested and placed in the space between the rectum and urethra. The viability of lap was favourable, without infection or necrosis. The patient could walk the next day, and was discharged 2 weeks later without fecaluria or liquid stool. We conclude that the gluteal-fold adipofascial perforator flap offers excellent functional advantages in rectourethral fistula reconstruction with minimal morbidity at the donor site

Visualization of nerve fibers around the carotid bifurcation with use of a 9.4 Tesla microscopic magnetic resonance diffusion tensor imaging with tractography

BACKGROUND: Precise imaging of nerves have been challenging in the head and neck region, mainly due to low spatial resolution. Here, we investigated how nerves in the head and neck region could be visualized using an ultra-high magnetic field MR system. METHODS: We used formol-carbol-fixed human cadaveric necks and obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra-high magnetic field MR system. Afterward, we prepared tissue sections and checked the anatomic relationships between the neurons and the carotid artery in order to confirm that the visualized fibers are indeed neuron fibers. RESULTS: We were able to identify nerves, including the vagus nerve, the hypoglossal nerve, and the spinal-accessory nerve. Hematoxylin-eosin stained histological sections confirmed neuron fibers in the same anatomic position. CONCLUSION: This technique has the feasibility to be applied for a more accurate anatomic understanding, maybe even close to a histological level

¿De vuelta a Los ocho años? A propósito de La guerra de Figueres, de Guillermo Villegas Hoffmaister

El libro de Guillermo Villegas Hoffmeister, “La guerra de Figueres”, tiene sin duda el subtítulo exacto Crónica de ocho años, porque eso es lo que es. Basado en alguna documentación escrita, en sus propios recuerdos personales y en una revisión de los periodos de la década de 1940, la obra se presenta ante todo como un producto de entrevistas realizadas por el autor a distintos personajes de la época. El resultado final es una narrativa descriptiva y parcializada, que combina alguna información interesante con datos sin importancia y algunas notables inexactitudes históricas: por ejemplo, el autor afirma que ¡el partido republicano nacional fue fundado por Maximiliano Fernández en 1909!, y en lo que parece ser producto de un lamentable descuido de él y de la EUNED, fecha la batalla de tejar el 13 de marzo en vez del 13 de abril de 1948…UCR::Vicerrectoría de Investigación::Unidades de Investigación::Artes y Letras::Centro de Investigación en Identidad y Cultura Latinoamérica (CIICLA

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead