Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinum A toxin

The intracellular action on exocytosis of botulinim A toxin and constituent chains was studied using permeabilized isolated nerve endings from the rat neural lobe. The release of the neuropeptide vasopressin was measured by radioimmunoassay. In the presence of the reducing agent dithiothreitol, the two-chain form of botulinum A toxin inhibited vasopressin release induced by 10 μM free calcium. Half maximal inhibition was obtained with 15 nM botulinum A toxin. In the absence of the heavy chain the light chain of the toxin strongly inhibited exocytosis with a half maximal effect of 2.5 nM. The inhibitory effects on secretion could be prevented by incubating the light chain with an immune serum against botulinum A toxin. The heavy chain of botulinum A toxin did not affect vasopressin release. However, it prevented the inhibitory effects of the light chain on stimulated exocytosis. It is concluded that botulinum A toxin inhibits the calcium-dependent step leading to exocytosis by interfering with a target present in the isolated and permeabilized nerve terminals. The functional domain of this neurotoxin, which is responsible for the inhibition of vasopressin release, is present in its light chain

Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinum A toxin

The intracellular action on exocytosis of botulinim A toxin and constituent chains was studied using permeabilized isolated nerve endings from the rat neural lobe. The release of the neuropeptide vasopressin was measured by radioimmunoassay. In the presence of the reducing agent dithiothreitol, the two-chain form of botulinum A toxin inhibited vasopressin release induced by 10 μM free calcium. Half maximal inhibition was obtained with 15 nM botulinum A toxin. In the absence of the heavy chain the light chain of the toxin strongly inhibited exocytosis with a half maximal effect of 2.5 nM. The inhibitory effects on secretion could be prevented by incubating the light chain with an immune serum against botulinum A toxin. The heavy chain of botulinum A toxin did not affect vasopressin release. However, it prevented the inhibitory effects of the light chain on stimulated exocytosis. It is concluded that botulinum A toxin inhibits the calcium-dependent step leading to exocytosis by interfering with a target present in the isolated and permeabilized nerve terminals. The functional domain of this neurotoxin, which is responsible for the inhibition of vasopressin release, is present in its light chain

The light chain of tetanus toxin inhibits calcium-dependent vasopressin release from permeabilized nerve endings

The effects of tetanus toxin and its light and heavy chain subunits on vasopressin release were investigated in digitonin-permeabilized neurosecretory nerve terminals isolated from the neural lobe of the rat pituitary gland. Exocytosis was induced by challenging the permeabilized nerve endings with micromolar calcium concentrations. Tetanus toxin inhibited vasopressin release only in the presence of the reducing agent dithiothreitol. This effect was irreversible. The purified light chain of tetanus toxin strongly inhibited exocytosis in a dose-dependent manner with half-maximal effect at c. 10 nM. The action of the light chain was observed after only 2.5 min of preincubation. Separated heavy chain subunit had no effect on hormone secretion. Inhibition of vasopressin release could be prevented by preincubating the light chain of tetanus toxin with an immune serum against tetanus toxin. The data clearly demonstrate that in mammalian neurosecretory nerve endings tetanus toxin acts at a step downstream from the activation by Ca2+ of the exocytotic machinery and that the functional domain of this toxin is confined to its light chain

Trends in carbapenemase-producing Enterobacteriaceae, France, 2012 to 2014.

In 2014, a total of 2,976 Enterobacteriaceae isolates with decreased susceptibility to carbapenems were received at the French Associated National Reference Center for Antibiotic Resistance (NRC) and were characterised for their molecular resistance mechanism to carbapenems and compared with results obtained during 2012 and 2013.The overall number of enterobacterial isolates with decreased susceptibility to carbapenems received at the NRC rapidly increased (more than twofold in two years) with a growing proportion of carbapenemase producers (23.1% in 2012 vs 28.6% in 2013 vs 36.2% in 2014). Between 2012 and 2014, the main carbapenemase type was OXA-48, with an increase in OXA-48 variants (mostly OXA-181) and NDM producers, whereas the number KPC producers decreased. We identified a potential spread of OXA-181 producers in the tropical region of Africa. Finally, OXA-48 and OXA-48-related enzymes remained the predominant carbapenemases in France. The number of carbapenemase-producing Escherischia coli isolates was multiplied by fivefold between 2012 and 2014, suggesting a possible dissemination in the community

Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinum A toxin

The intracellular action on exocytosis of botulinim A toxin and constituent chains was studied using permeabilized isolated nerve endings from the rat neural lobe. The release of the neuropeptide vasopressin was measured by radioimmunoassay. In the presence of the reducing agent dithiothreitol, the two-chain form of botulinum A toxin inhibited vasopressin release induced by 10 μM free calcium. Half maximal inhibition was obtained with 15 nM botulinum A toxin. In the absence of the heavy chain the light chain of the toxin strongly inhibited exocytosis with a half maximal effect of 2.5 nM. The inhibitory effects on secretion could be prevented by incubating the light chain with an immune serum against botulinum A toxin. The heavy chain of botulinum A toxin did not affect vasopressin release. However, it prevented the inhibitory effects of the light chain on stimulated exocytosis. It is concluded that botulinum A toxin inhibits the calcium-dependent step leading to exocytosis by interfering with a target present in the isolated and permeabilized nerve terminals. The functional domain of this neurotoxin, which is responsible for the inhibition of vasopressin release, is present in its light chain

Assessing Expectations: Towards a Toolbox for an Ethics of Emerging Technologies

In recent years, several authors have argued that the desirability of novel technologies should be assessed early, when they are still emerging. Such an ethical assessment of emerging technologies is by definition focused on an elusive object. Usually promises, expectations, and visions of the technology are taken as a starting point. As Nordmann and Rip have pointed out in a recent article, however, ethicists should not take for granted the plausibility of such expectations and visions. In this paper, we explore how the quality of expectations on emerging technologies might be assessed when engaging in a reflection on the desirability of emerging technologies. We propose that an assessment of expectations’ plausibility should focus on statements on technological feasibility, societal usability, and desirability of the expected technology. Whereas the feasibility statement and, to a lesser extent, the usability statements are frequently quite futuristic, the claims on desirability, by contrast, often display a conservative stance towards the future. Assessing the quality of expectations and visions on behalf of emerging technologies requires, then, a careful and well-directed use of both skepticism and imagination. We conclude with a brief overview of the tools and methods ethicists could use to assess claims made on behalf of emerging technologies and improve the ethical reflection on them

Management of female genital mutilation / cutting-related obstetric complications: a training evaluation

Although female genital mutilation/cutting (FGM/C) is a prevalent practice in Liberia, healthcare workers lack the capacity to provide adequate care for FGM/C survivors. Therefore, Liberian nurses, physician assistants, midwives and trained traditional midwives were trained in sexual, obstetric and psychosocial care for FGM/C survivors in 2019. Through questionnaires, we assessed knowledge acquisition, trainee attitudes towards FGM/C care and acceptability to implement WHO-endorsed recommendations. The questionnaires were analyzed using descriptive statistics for quantitative data and an inductive approach for qualitative data. A total of 99 female and 34 male trainees participated. Most trainees perceived FGM/C as harmful to women''s health, as a violation of women''s rights and showed a willingness to change their clinical practice. While 82.8% (n = 74/90) perceived their role in advocating against FGM/C, 10.0% (n = 9/90) felt that they should train traditional circumcisers to practice FGM/C safely. The pre-training FGM/C knowledge test demonstrated higher scores among physician assistants (13.86 ± 3.02 points) than among nurses (12.11 ± 3.12 points) and midwives (11.75 ± 2.27 points). After the training, the mean test score increased by 1.69 points, from 12.18 (±2.91) points to 13.87 (±2.65) points. The trainings successfully increased theoretical knowledge of FGM/C-caused health effects and healthcare workers'' demonstrated willingness to implement evidence-based guidelines when providing care to FMG/C survivors

Cross-reaction of naturally-produced β-lactamases from Citrobacter farmeri and Citrobacter amalonaticus with immunological detection of CTX-M enzymes.

The NG-Test CTX-M MULTI immunochromatographic assay has been developed to identify CTX-M-type β-lactamases in Enterobacterales, being the most widespread extended-spectrum β-lactamases. We showed here that the chromosomally-encoded ß-lactamases from Citrobacter farmeri and Citrobacter amalonaticus generated false-positive NG-Test CTX-M MULTI results, compromising the specificity of the test