Aqueous humor concentrations of topically administered caspofungin in rabbits.

Background: The echinocandin caspofungin (CAS) is a novel antifungal drug with fungicidal in vitro activity against all Candida spp., which are the most frequent cause of fungal keratitis. Penetration of CAS through the cornea into the aqueous humor after topical administration was investigated.

Aqueous humor concentration of voriconazole after topical administration in rabbits.

Objectives: Voriconazol is a triazole antifungal drug with in vitro fungicidal activity against all Candida spp., Fusarium spp. and Aspergillus spp.

Expression and function of somatostatin receptors in peripheral nerve sheath tumors.

Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations.

Analysis of a single nucleotide polymorphism in codon 388 of the FGFR4 gene in malignant gliomas.

The FGFR4 codon 388 polymorphism (Arg(388), Arg/Gly(388) or Gly(388)) was determined in glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), diffuse astrocytomas (DA), and control muscles. Arg(388) was rare in AA, GBM, muscles, and was absent in DA. The Arg/Gly(388) and the Gly(388) frequency was equal among GBM and controls.

Different activation of mitogen-activated protein kinase and Akt signaling is associated with aggressive phenotype of human meningiomas.

Purpose: Activation of intracellular signaling cascades has been implicated in the growth control of benign meningiomas, but their role for meningioma progression and outcome is unknown. Here we determined the expression and function of proteins involved in mitogen-activated protein kinase (MAPK) and phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and malignant meningiomas and studied their association with clinicopathologic data including meningioma recurrence.

Experimental Design: Expression of various MAPK and PI3K signaling proteins was determined in 70 primary meningiomas and, if present, in recurrent tumors by immunohistochemistry and Western blotting.

Alterations of cell cycle regulators in gliomatosis cerebri.

Gliomatosis cerebri (GC) is regarded as a rare glial neoplasm of unknown origin, and a detailed analysis of molecular alterations underlying this disease has started only recently. However, because GC characteristically affects large parts of the brain and spinal cord, the distribution of genetic alterations may be highly variable between different tumor areas. Additionally, tumor areas with varying degrees of differentiation may be present, raising the possibility to model the genetic events associated with astrocytoma progression.

Hereditary lattice corneal dystrophy is associated with corneal amyloid deposits enclosing C-terminal fragments of keratoepithelin.

Purpose: To investigate the molecular basis of hereditary lattice corneal dystrophy (LCD) type IIIA associated with corneal amyloid deposits afflicting several members of a four-generation family.

Methods: Histologic, immunohistochemical and biochemical studies were performed on corneal tissue samples obtained after perforating keratoplasty. DNA was extracted from peripheral blood leukocytes.

Single-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis.

One possible cause for the neuronal loss in sporadic amyotrophic lateral sclerosis (S-ALS) is an increase of free radicals, which may produce oxidative damage to susceptible biomolecules, which, in turn, can damage the mitochondrial DNA (mtDNA). Following laser microdissection of single motor neurons from paraffin-embedded autopsy tissue, we analyzed the presence of a common mtDNA deletion, the 5 kb common deletion (CD). Spinal cord neurons showed slightly higher CD detection rate in patients than controls (94% vs 75%).

Region-specific analysis of mitochondrial DNA deletions in neurodegenerative disorders in humans.

Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) aberrations has been implicated in the neuronal death in neurodegenerative disorders. Significant neuronal damage can occur if the percentage of mtDNA mutations may reach a critical threshold. mtDNA mutations also accumulate during normal aging.

Effects of axonal injury on ganglion cell survival and glutamate homeostasis.

Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Optic nerve crush can be used to explore histologic and molecular changes in traumatic central nervous system malfunction. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush have not been elucidated, glutamate antagonists can protect retinal ganglion cells after axotomy.

Prognostic relevance of MAPK expression in glioblastoma multiforme.

The objective of this study was to determine the immunoexpression pattern of the mitogen-activated protein kinase (MAPK), and related signalling proteins [protein kinase C (PKC), phospholipase Cgamma (PLCgamma)], in glioblastoma multi-forme, and to investigate their prognostic value. Paraffin-embedded biopsy samples from 26 patients [13 patients with long-term survival (LTS; N=13; median 28 months, range 13-76 months), and, for comparison, 13 patients with short-term survival (STS; N=13; median 7 months, range 1-12 months)] were investigated for the immunoexpression of MAPK, the activated pMAPK, PKC, PLCgamma, EGFR, and PTEN. Additionally, the MIB-1 proliferation index was determined.

Combined topical fluconazole and corticosteroid treatment for experimental Candida albicans keratomycosis.

Purpose: To determine the most efficient time point and concentration of topical corticosteroids in Candida albicans keratitis treated with fluconazole.

Methods: Corneas of 105 rabbits were infected with viable yeast cells of C. albicans (2.

GM1 ganglioside administration protects spinal neurons after glutamate excitotoxicity.

Injury of the nervous system initiates a cascade of signal transduction including a rise in extracellular glutamate which leads to subsequent secondary neuronal loss. Excitotoxicity is known to play a crucial role in cell death spinal cord trauma. Gangliosides, particularly monosialogangliosides (GM1), are protective against various neurological insults, including excitotoxicity.

Changes of retinal glutamate transporter GLT-1 mRNA levels following optic nerve damage.

Purpose: Under physiological conditions, levels of the excitatory neurotransmitter glutamate within the retina are regulated by retinal glutamate transporters to prevent toxic accumulation. Alterations in this glutamate buffering have been implicated in retinal ganglion cell (RGC) death. We quantified the changes in the level of glutamate transporter mRNA in a model of acute rat optic nerve injury.

Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice.

Traumatic axonal injury (TAI) is one of the most important pathologies associated with closed head injury, and contributes to ensuing morbidity. The authors evaluated the potential role of calpains in TAI using a new model of optic nerve stretch injury in mice. Male C57BL/6 mice were anesthetized, surgically prepared, and subjected to a 2.