Hypoosmotic swelling increases protein tyrosine nitration in cultured rat astrocytes.
Astrocyte swelling is observed in different types of brain injury. We studied a potential contribution of swelling to protein tyrosine nitration (PTN) by using cultured rat astrocytes exposed to hypoosmotic (205 mosmol/L) medium. Hypoosmolarity (2 h) increases total PTN by about 2-fold in 2 h. The hypoosmotic PTN is significantly inhibited by the NMDA receptor antagonist MK-801, the nitric oxide synthase (NOS) inhibitor L-NMMA, the extracellular Ca2+ chelator EGTA and the calmodulin antagonist W13, suggesting the involvement of NMDA receptor activation, influx of extracellular Ca2+ and Ca2+/calmodulin-dependent NO synthesis. Further, superoxide dismutase plus catalase and uric acid strongly inhibit hypoosmotic PTN, suggesting the involvement of the toxic metabolite peroxynitrite (ONOO-) as a nitrating agent. Hypoosmotic astrocyte swelling rapidly stimulates generation of reactive oxygen intermediates; this process is prevented by MK-801 and EGTA. In addition, MK-801 inhibits the hypoosmotic elevation of [Ca2+]i. The findings support the view that astrocyte swelling as induced, for example, by toxins relevant for hepatic encephalopathy is sufficient to produce oxidative stress and PTN and thus contributes to altered astroglial and neuronal function.
The effectiveness and clinical usefulness of the hypo-osmotic swelling (HOS) test in predicting successful conception in couples in which men with mild male-factor infertility criteria were undergoing a timed vaginal inter-course protocol. One hundred couples, in which mild male infertility was the only abnormality, were included in the study. Semen was analyzed according to standard World Health Organization (WHO) criteria and subjected to the HOS test. Patients were divided into 2 groups: group 1 (n = 39) with normal HOS test and group 2 (n = 61) with abnormal HOS test. All women underwent three consecutive cycles of follicular growth ultrasound monitoring and timed intercourse. Ten couples were exclude from the study. Ten clinical pregnancies were achieved in group 1 with a pregnancy rate per patient and per cycle of 28.5% and 9.5%, respectively. In group 2, 6 pregnancies were achieved, with a pregnancy rate per patient and per cycle of 10.9% and 3.6%, respectively. Both pregnancy rates per patients and per cycle was significantly higher (P < .05) in group 1 than in group 2. The HOS test may be considered an easy and reliable test in identifying among subfertile men those who have a greater possibility of causing pregnancy.