Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation

Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP.     

Perforated duodenal ulcer and cigarette smoking.

Whilst the association between smoking and peptic ulceration has been reported previously, the relationship between smoking and the complications of ulcers, such as perforation, bleeding or acute painful exacerbation, has not been examined. In a retrospective study comparing 275 emergency admissions for peptic ulcer with 275 controls, cigarette smoking was significantly more common only in those with a perforated duodenal ulcer. Of 128 patients with perforated duodenal ulcers, 110 (86%) were cigarette smokers compared with 65 (51%) of the 128 matched controls (X2, P less than 0.01). Cigarette smoking in patients with bleeding or acutely exacerbated ulcers was not significantly more common than in controls. These findings strongly suggest a particular association between smoking and perforated duodenal ulcer.     

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

The neurosteroid allopregnanolone (ALLO) or 3α-OH-5α-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3β position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3β-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3β-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3β-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3β-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3β-steroids can act as positive GABA_A receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3β-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.     

Élaboration d’un guide d’information SOR SAVOIR PATIENT à l’usage des personnes malades et de leurs proches sur la vie intime et sexuelle pendant et après un cancer : l’étape d’état des lieux

Since 1998, the French National Federation of Comprehensive Cancer Centres (FNCLCC) has led an information program dedicated to patients and their relatives: the SOR SAVOIR PATIENT (SSP) program. The program is provided by the FNCLCC, the twenty French regional cancer centres (CLCC), the National League Against Cancer (LCC), the French National Cancer Institute (INCa), the French Hospital Federation (FHF), the National Oncology Federation of Regional and University Hospitals (FNCCHRU), the French Oncology Federation of General Hospitals (FFCHG), the National Private Hospital Union for Oncology (UNHPC), the International Union Against Cancer (UICC) and a large number of learned societies. The methodology of the program adheres to the quality criteria established for publishing documents containing information for patients. Issues related to the sexual health of cancer patients and their partners too often remain underestimated and even completely neglected by health professionals, although healthcare providers are increasingly interested in this area and patients frequently confront them with questions about this aspect of their lives. The development of an SOR SAVOIR PATIENT informational guide on the various issues related to sexuality during and after cancer treatment constitutes a first step in addressing the needs of cancer patients and others concerned. This article describes the first stage in the development of a specific SOR SAVOIR PATIENT guide that focuses on the general availability of informational material in French on the sexual health of patients and their partners during and after cancer treatment.