Effect of SCUBA Diving on Ophthalmic Parameters.

Background and Objective: Several cases of central serous chorioretinopathy (CSC) in divers have been reported in our medical retina center over the past few years. This study was designed to evaluate possible changes induced by SCUBA diving in ophthalmic parameters and especially subfoveal choroidal thickness (SFCT), since the choroid seems to play a crucial role in physiopathology of CSC. Materials and Methods: Intraocular pressure (IOP), SFCT, pachymetry, flow-mediated dilation (FMD), blood pressure, and heart rate were measured in 15 healthy volunteer divers before diving, 30 and 60 min after a standard deep dive of 25 m depth for 25 min in a dedicated diving pool (NEMO 33). Results: SFCT reduces significantly to 96.63 ± 13.89% of pre-dive values (p = 0.016) 30 min after diving. It recovers after 60 min reaching control values. IOP decreases to 88.05 ± 10.04% of pre-dive value at 30 min, then increases to 91.42 ± 10.35% of its pre-dive value (both p < 0.0001). Pachymetry shows a slight variation, but is significantly increased to 101.63 ± 1.01% (p = 0.0159) of the pre-dive value, and returns to control level after 60 min. FMD pre-dive was 107 ± 6.7% (p < 0.0001), but post-dive showed a diminished increase to 103 ± 6.5% (p = 0.0132). The pre-post difference was significant (p = 0.03). Conclusion: Endothelial dysfunction leading to arterial stiffness after diving may explain the reduced SFCT observed, but SCUBA diving seems to have miscellaneous consequences on eye parameters. Despite this clear influence on SFCT, no clear relationship between CSC and SCUBA diving can be drawn.

Post-surgical left oculomotor nerve neuromyotonia: Cause or coincidence?

Ocular neuromyotonia (ONM) is characterized by episodes of binocular diplopia usually triggered by an eye movement requiring contraction of the affected extraocular muscle. It consists of an involuntary, sometimes painful contraction of one or more extraocular muscles. It is most often secondary to radiotherapy of the para-sellar region, although other aetiologies have been reported. Some cases do not have a clearly identified aetiology and are classified as idiopathic. Most cases of ONMs are unilateral but bilateral ONMs have also been described.1-4 We report a case of left ONM in a 55-year-old female patient, several weeks after simultaneous surgical resection of two meningiomas, situated on the right side (Simpson II). The particularity of this case is linked to its puzzling presentation, its similarity with spasm of the near reflex and the putative mechanism through which surgery might have precipitated the symptoms.

Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models.

Oncolytic virotherapy is a potential treatment modality under investigation for various malignancies including malignant brain tumors. Unlike some other natural or modified viruses that show oncolytic activity against cerebral neoplasms, the rodent parvovirus H-1 (H-1PV) is completely apathogenic in humans. H-1PV efficiently kills a number of tumor cells without harm to corresponding normal ones. In this study, the concept of H-1PV-based virotherapy of glioma was tested for rat (RG-2 cell-derived) and for human (U87 cell-derived) gliomas in immunocompetent and immunodeficient rat models, respectively. Large orthotopic rat and human glioma cell-derived tumors were treated with either single stereotactic intratumoral or multiple intravenous (iv) H-1PV injections. Oncolysis was monitored by magnetic resonance imaging and proven by histology. Virus distribution and replication were determined in brain and organs. In immunocompetent rats bearing RG-2-derived tumors, a single stereotactic intratumoral injection of H-1PV and multiple systemic (iv) applications of the virus were sufficient for remission of advanced and even symptomatic intracranial gliomas without damaging normal brain tissue or other organs. H-1PV therapy resulted in significantly improved survival (Kaplan-Meier analysis) in both the rat and human glioma models. Virus replication in tumors indicated a contribution of secondary infection by progeny virus to the efficiency of oncolysis. Virus replication was restricted to tumors, although H-1PV DNA could be detected transiently in adjacent or remote normal brain tissue and in noncerebral tissues. The results presented here and the innocuousness of H-1PV for humans argue for the use of H-1PV as a powerful means to perform oncolytic therapy of malignant gliomas.

Cytosolic activation of cathepsins mediates parvovirus H-1-induced killing of cisplatin and TRAIL-resistant glioma cells.

Gliomas are often resistant to the induction of apoptotic cell death as a result of the development of survival mechanisms during astrocyte malignant transformation. In particular, the overexpression of Bcl-2-family members interferes with apoptosis initiation by DNA-damaging agents (e.g., cisplatin) or soluble death ligands (e.g., TRAIL). Using low-passage-number cultures of glioma cells, we have shown that parvovirus H-1 is able to induce death in cells resistant to TRAIL, cisplatin, or both, even when Bcl-2 is overexpressed. Parvovirus H-1 triggers cell death through both the accumulation of lysosomal cathepsins B and L in the cytosol of infected cells and the reduction of the levels of cystatin B and C, two cathepsin inhibitors. The impairment of either of these effects protects glioma cells from the viral lytic effect. In normal human astrocytes, parvovirus H-1 fails to induce a killing mechanism. In vivo, parvovirus H-1 infection of rat glioma cells intracranially implanted into recipient animals triggers cathepsin B activation as well. This report identifies for the first time cellular effectors of the killing activity of parvovirus H-1 against malignant brain cells and opens up a therapeutic approach which circumvents their frequent resistance to other death inducers.

Inhibition of transcription-regulating properties of nonstructural protein 1 (NS1) of parvovirus minute virus of mice by a dominant-negative mutant form of NS1.

Nonstructural protein 1 (NS1) of minute virus of mice is involved in viral DNA replication, transcriptional regulation and cytotoxic action in the host cell. Viral DNA replication is dependent on the ability of NS1 to form homo-oligomers. To investigate whether oligomerization is required for NS1 transcriptional activities, a functionally impaired mutant derivative of NS1 that was able to interact with the wild-type (wt) protein and inhibit its activity in a dominant-negative manner was designed. This mutant provided evidence that transactivation of the parvoviral P38 promoter and transinhibition of a heterologous promoter by NS1 were both affected by the co-expression of the wt and the dominant-negative mutant form of NS1. These results indicate that additional functions of NS1, involved in promoter regulation, require oligomer formation.