Occurrence of the Interference of Sperm-Associated Antibodies on Sperm Fertilizing Ability as Evaluated by the Sperm-Zona Pellucida Binding Test and by the TEST-Yolk Buffer Enhanced Sperm Penetration Assay

PROBLEM: This study was performed to evaluate the occurrence as well as the level of the interference of sperm-associated antibodies on fertilization process. METHOD: Motile sperm suspensions from 28 infertile patients with high degree of autoimmunization against the sperm head were tested with the zona pellucida (ZP) binding test and with the sperm penetration assay (SPA) enhanced with TEST-yolk buffer. Both tests were also performed using donor sperm exposed and non-exposed to the patients' circulating sperm antibodies. RESULTS: A low ZP-binding was exhibited by sperm from 50% of patients with normal semen profile. All normozoospermic patients with low ZP-binding showed circulating sperm-antibodies with inhibitory effect on ZP-binding, while no patient with normal ZP-binding showed circulating sperm-antibodies with inhibitory effect. No normozoospermic patient exhibited a negative SPA result, and only in 16% of cases the penetration index was slightly less than 2 (the lowest value exhibited by fertile controls). Circulating antisperm-antibodies did not significantly affect the hamster egg penetration. CONCLUSION: Even in the presence of high degree of autoimmunization against the sperm-head, sperm fusion with oolemma is not impaired after sperm preincubation with TEST-yolk buffer, while an impairment of the ZP-binding is demonstrable in half cases, when non-immunologic factors are excluded. A substantial role in this interference is likely exerted by IgG antibodies transuded from the blood into the genital tract.     

KRAS mutational status assessment in patients with metastatic colorectal cancer: are the clinical implications so clear?

HEBBAR M., FOURNIER P. & ROMANO O. (2010) European Journal of Cancer Care 19 , 145–166
KRAS mutational status assessment in patients with metastatic colorectal cancer: are the clinical implications so clear? The CRYSTAL study demonstrated an advantage in terms of objective response and progression‐free survival for the FOLFIRI–cetuximab combination compared with first‐line FOLFIRI for patients with metastatic colorectal cancer. The results of an ancillary biological study with screening for a KRAS gene mutation in 540 patients were reported at the 2008 American Society of Clinical Oncology congress. The analysis confirmed the value of adding cetuximab only in the absence of KRAS mutation. These results led to recommend restriction of the use of cetuximab in Europe to patients with a tumour bearing wild‐type KRAS. How should this apparent simplification be integrated into clinical practice? The FOLFIRI–cetuximab combination is certainly a useful supplementary first‐line option although its place in relation to other high‐dose regimens (high‐dose FOLFIRI, FOLFOXIRI or FOLFOX‐7), conventional chemotherapy plus bevacizumab, or even a fluoropyrimidine alone in the case of unresectable metastases, has yet to be specified. For subsequent lines, no study has prospectively assessed the value of the chemotherapy–anti‐epidermal growth factor receptor combination as a function of KRAS status. Should the absence of objective response constantly observed in retrospective analyses in patients with a tumour presenting a KRAS mutation definitively exclude these patients while stable disease (and potentially a slight gain in survival) may be obtained?     

Baseline Transition Sleep and Associated Sleep Episodes are Related to the Learning Ability of Rats

The EEGs of 18 adult male Wistar rats were recorded during a baseline session lasting 7 h (day 1). The following day, rats were trained for a 2-way active avoidance task in an automated shuttle-box. A retention test was scheduled on the third day. On the basis of the number of avoidances scored during the training and retention sessions, rats were assigned to a fast-learning group (FL; achieving criterion during the training session), a slow-learning group (SL; achieving criterion in the retention test session), and a nonlearning group (NL; failing to achieve criterion). Vigilance states were determined by analyzing EEG data in 5-s epochs and calculating EEG power spectra of consecutive time intervals as short as 1 s. This high-resolution method led to the identification of transition sleep episodes that followed slow-wave sleep (SS) and were followed by waking (TS → W) or by paradoxical sleep (TS → PS). Comparison of the baseline sleep variables of the 3 behavioral groups revealed the presence of several significant differences. These observations were confirmed by the results of correlative analyses between baseline sleep variables and number of avoidances scored during the training and retention sessions. The most reliable indices of the capacity to learn the avoidance task were the amounts of SS preceding the TS → W or the TS → PS sequence, and the amounts of either component of the latter sequence. These variables displayed markedly higher values in FL rats. In addition, the amount of SS preceding TS → W and the amount of TS → (W) were significantly correlated with the number of avoidances scored during the training session. On the other hand, 1. SS → (PS) and (SS) → PS episodes were longer in NL rats than in SL or FL rats, respectively; and 2. the duration of SS → (PS) episodes was inversely correlated with the number of avoidances of the first training period. The data are interpreted to suggest that TS and associated sleep episodes may predict the acquisition of the avoidance task, and the episodes of SS → PS not associated with TS may predict the retention of innate responses, such as freezing or escapes.