An agonist of CXCR4 induces a rapid recovery from the neurotoxic effects of Vipera ammodytes and Vipera aspis venoms.

People bitten by Alpine vipers are usually treated with antivenom antisera to prevent the noxious consequences caused by the injected venom. However, this treatment suffers from a number of drawbacks and additional therapies are necessary. The venoms of Vipera ammodytes and of Vipera aspis are neurotoxic and cause muscle paralysis by inducing neurodegeneration of motor axon terminals because they contain a presynaptic acting sPLA2 neurotoxin. We have recently found that any type of damage to motor axons is followed by the expression and activation of the intercellular signaling axis consisting of the CXCR4 receptor present on the membrane of the axon stump and of its ligand, the chemokine CXCL12 released by activated terminal Schwann cells. We show here that also V. ammodytes and V. aspis venoms cause the expression of the CXCL12-CXCR4 axis. We also show that a small molecule agonist of CXCR4, dubbed NUCC-390, induces a rapid regeneration of the motor axon terminal with functional recovery of the neuromuscular junction. These findings qualify NUCC-390 as a promising novel therapeutics capable of improving the recovery from the paralysis caused by the snakebite of the two neurotoxic Alpine vipers.

Botulinum Neurotoxins: Mechanism of Action.

Botulinum neurotoxins (BoNTs) are a growing family of bacterial protein toxins that cause botulism, a rare but often fatal animal and human disease. They are the most potent toxins known owing to their molecular architecture, which underlies their mechanism of action. BoNTs target peripheral nerve terminals by a unique mode of binding and enter into their cytosol where they cleave SNARE proteins, thus inhibiting the neurotransmitter release. The specificity and rapidity of binding, which limits the anatomical area of its neuroparalytic action, and its reversible action make BoNT a valuable pharmaceutical to treat neurological and non-neurological diseases determined by hyperactivity of cholinergic nerve terminals. This review reports the progress on our understanding of how BoNTs cause nerve paralysis highlighting the different steps of their molecular mechanism of action as key aspects to explain their extreme toxicity but also their unique pharmacological properties.

[Methicillin-resistant staphylococci in pediatric resuscitation]. / Stafilococchi meticillino-resistenti in rianimazione pediatrica.

OBJECTIVE: To evaluate the incidence of colonization and infection by methicillin-resistant in PICU. DESIGN: Prospective cohort study during 2 years for the surveillance of nosocomial infections. SETTING: Four beds Pediatric Intensive Care Unit. PATIENTS: We studied two-hundred patients with duration of hospitalization longer than 24 hours out of the 255 patients who were hospitalized during the same period. METHODS: The patients were divided in two groups according to the presence or the absence of MRS. The difference of the two populations were compared using the t-test and the CATANOVA: Wilcoxon's test was used to analyze the relation between the two values. The results were significant when p = 0.05 and Ct = 3.81. RESULTS: Fourty patients (20%) were colonized or infected by MRS with two seasonal peaks which were not correlated with the amount of index work. Nine patients were already colonized at entrance in PICU (4.5%) and the rate of infected patients versus infections was 1.5% (3 patients with 3 clinical manifestations). The presence of MRS in the different sections of the hospital could be shown. The rate of PICU-acquired colonization was 12.5% (25), the rate of PICU-acquired infected patients was only 2% (4), the infections rate was 3.5% (7 events). The average time which occurred the colonization by MRS to happen was 10,1 days from the day of hospitalization on, which is longer than that of the other germs (p = 0.001). Clinically the infection by MRS was localized as follows: 3 septicemiae, 2 pneumoniae and 2 muco-cutaneous infections. Most the patients with carriage of the MRS were prematures or newborns who had a long stay in PICU, who underwent invasive diagnostic and therapeutic treatment and who had a previously long stay in other department of the hospital. The stay in the PICU lasted longer in those patients who had a MRS carriage. They furthermore had a lower mortality rate (12.5%) than the other patients (Cc = 0.976); the 4 infected patients survived. CONCLUSIONS: The clinical impact of MRS in terms of morbidity and mortality in this PICU is modest. The prevention and limitation of the spread of MRS could be obtained by simple but essential measures of control.

[Comparison between bacterial contamination of the circular circuit and of the non-rebreathing circle used with an antibacterial filter]. / Confronto tra la contaminazione batterica del circuito circolare e quella del circuito non rebreathing usato con un filtro antibatterico.

In order to evaluate whether the risk of bacterial contamination increased during low-flow anaesthesia without bacterial filter compared with non-rebreathing anaesthesia with a disposable bacterial filter, two groups of patient were studied. In the first group a disposable circle absorber system was changed once daily, thus it was used for several patients. In the second group a non-rebreathing system was connected to a disposable bacterial filter before each surgical procedure. Samples for microbiological examination were taken preoperatively from the oropharynx and postoperatively from three locations in the circle system and in the non-rebreathing system. No difference in rates of circuit contamination were observed between the two groups.

Intensive care units as a source of methicillin-resistant Staphylococcus aureus.

Over a 12 month period, 209 isolates of methicillin resistant Staphylococcus aureus (MRSA) were obtained in 39 patients admitted to an ICU. In 23 patients MRSA was the major pathogen, producing either pneumonia, bacteremia or wound infection. In eight patients death was directly related to the MRSA infection. This study suggests an increasing occurrence of MRSA infections in ICU and the need to adopt control measures.