Intragastric and Intranasal Administration of Lactobacillus paracasei NCC2461 Modulates Allergic Airway Inflammation in Mice.

Introduction. Preclinical and clinical evidences for a role of oral probiotics in the management of allergic diseases are emerging. Aim. We aimed at testing the immunomodulatory effects of intranasal versus intragastric administration of Lactobacillus paracasei NCC2461 in a mouse model of allergic airway inflammation and the specificity of different probiotics by comparing L. paracasei NCC2461 to Lactobacillus plantarum NCC1107. Methods. L. paracasei NCC2461 or L. plantarum NCC1107 strains were administered either intragastrically (NCC2461) or intranasally (NCC2461 or NCC1107) to OVA-sensitized mice challenged with OVA aerosols. Inflammatory cell recruitment into BALF, eotaxin and IL-5 production in the lungs were measured. Results. Intranasal L. paracasei NCC2461 efficiently protected sensitized mice upon exposure to OVA aerosols in a dose-dependent manner as compared to control mice. Inflammatory cell number, eotaxin and IL-5 were significantly reduced in BALF. Intranasal supplementation of L. paracasei NCC2461 was more potent than intragastric application in limiting the allergic response and possibly linked to an increase in T regulatory cells in the lungs. Finally, intranasal L. plantarum NCC1107 reduced total and eosinophilic lung inflammation, but increased neutrophilia and macrophages infiltration. Conclusion. A concerted selection of intervention schedule, doses, and administration routes (intranasal versus intragastric) may markedly contribute to modulate airway inflammation in a probiotic strain-specific manner.

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

BACKGROUND: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. RESULTS: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.

Hypertension and intra-operative incidents: a multicentre study of 125000 surgical procedures in Swiss hospitals

Background: It is debated whether chronic hypertension increases the risk of cardiovascular incidents during anaesthesia. Methods: We studied all elective surgical operations performed in adults under general or regional anaesthesia between 2000 and 2004, in 24 hospitals collecting computerised clinical data on all anaesthetia since 1996. The focus was on cardiovascular incidents, though other anaesthesia-related incidents were also evaluated. Results: Among 124 939 interventions, 27 881 (22%) were performed in hypertensive patients. At least one cardiovascular incident occurred in 7549 interventions (6% [95% CI 5.9-6.2%]). The average adjusted odds ratio of cardiovascular risk in patients with chronic hypertension was 1.38 (95% CI 1.27-1.49). However, across hospitals, adjusted odd ratios varied from 0.41 up to 2.25. Hypertension did not increase the risk of other incidents. Conclusions: Hypertensive patients are still at risk of intra-operative cardiovascular incidents. The heterogeneity of the risk to develop cardiovascular incidents varied across hospitals, despite taking into account casemix and hospital characteristics. These variations suggest that anaesthetic practices differ across anesthesia services