LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria

Cirioni, Oscar; Giacometti, Andrea; Ghiselli, Roberto; Bergnach, Cristina; Orlando, Fiorenza; Silvestri, Carmela; Mocchegiani, Federico; Licci, Alberto; Skerlavaj, Barbara; Rocchi, Marco; Saba, Vittorio; Zanetti, Margherita; Scalise, Giorgio

doi:10.1128/aac.50.5.1672-1679.2006

Cited by 138 publications

(122 citation statements)

References 39 publications

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“…One such substance is LL-37, a 37-amino-acid peptide, with widespread antimicrobial properties. [14][15][16][17] Saline induces a conformational change in LL-37, which completely inactivates its antimicrobial capacity. Thus, mixing saline with tracheal secretions, nasal secretions or saliva damages the innate antimicrobial properties of those secretions.…”

Section: Introductionmentioning

confidence: 99%

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU

et al. 2007

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Objective: Small quantities of normal saline are sometimes instilled into the endotracheal tube of intubated neonates, to assist with the removal of thick secretions and maintain patency of the endotracheal tube. However, saline is detrimental to the innate immune system of the upper airway mucosa, rapidly unfolding and inactivating antimicrobial peptides such as LL-37. We previously reported the preparation and feasibility testing of 'ETCare', a low-sodium, physiologically based solution for airway care, and we now report results of a randomized, masked, controlled, two-centered study testing ETCare vs sterile saline among 60 intubated NICU patients.Study Design: Sixty intubated NICU patients were randomized to having their airway care with ETCare vs saline. Three hypotheses were tested: (1) tolerance -patients will tolerate ETCare for airway care as well as they tolerate saline, (2) nosocomial infections -ETCare will result in fewer tracheal aspirates where organisms grow and fewer cases of nosocomial sepsis, and (3) chronic lung disuse -ETCare will result in fewer patients discharged home on supplemental O 2 .Result: Thirty NICU patients with an endotracheal tube in place were randomized to receive their airway care with ETCare, and 30 to receive their care with saline. Only the pharmacist was aware of the randomization; the two solutions were visually indistinguishable and were dispensed in identical syringes. Tolerance of the solutions was similar. The ETCare recipients had trends toward fewer positive blood cultures (odds ratios (OR), 0.48; 95% confidence interval (CI), 0.13 to 1.68), and fewer discharges home on supplemental O 2 (OR, 0.43; 95% CI, 0.14 to 1.32; P ¼ 0.075). Conclusion:On the basis of this study and our previous 10-patient feasibility trial, we maintain that, for airway care, intubated NICU patients tolerate ETCare as well as saline. Data from this study can be used in estimating the sample sizes needed for a phase III trial. We speculate that such a trial will demonstrate that, compared with saline, ETCare will result in fewer nosocomial infections and less chronic lung disease.

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Section: Introductionmentioning

confidence: 99%

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU

et al. 2007

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“…SA methicillin-resistant SA (MRSA) groups were injected intraperitoneally with virulent strain of MRSA in a dose of 2 × 10 9 colony forming units (CFU)/mL per rat. [10] The remaining four groups were divided as following: SA plus NS (SA + NS) group was administered water-alcohol extract of NS in a dose of 150 mg/kg b.w. daily.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Effect of gum arabic and Nigella sativa on T-helper1 and T-helper2 immune response in Wistar rats infected with methicillin-resistant Staphylococcus aureus

Abd-El-Hafez¹,

Ismael²,

Soliman³

et al. 2017

Natl J Physiol Pharm Pharmacol

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Background:The herbal medications are widely used in folk medicine for treatment of variable diseases and infection. Staphylococcus aureus (Sa) is a Gram-positive bacteria that cause severe organ affection, especially in the lung. Nigella sativa (NS) and gum arabic (GA) are probiotics with multi-beneficial effects for human health. Aims and Objectives: The current study was outlined to examine the protective effect of NS and GA against SA induced serum alterations and changes in cytokines and antioxidants expressions. Materials and Methods: A total of 42 male Wistar rats were allocated into six groups (6 each). Control group without any treatment; SA group in a dose of 2 × 10 9 colony forming units /mL per rat. Rats in 3-6 groups served as SA infected groups and received NS for Group 3 (150 mg/kg b.w. daily), GA plus SA for Group 4 (10% wt/vol. daily), and SA group received a mixture of NS plus GA for Group 5, and SA administered group received Lactobacillus for Group 6 as a positive control. NS and GA were administered 2 weeks before SA infection and continued for 1 week. Serum levels of cytokines and oxidative stress biomarkers were measured. Lung tissues were examined at molecular levels for mRNA expression of inflammatory cytokines and antioxidants. Results: SA induced a significant decrease in serum levels of interleukin -6 (IL-6), IL-2, and tumor necrosis factor -alpha. NS induced significant decrease on examined cytokines levels in SA (P < 0.05). GA did not induce any additive changes in cytokines. When both NA and GA were administered together, NS induced additive inhibitory effect. SA injection induced significant increase in serum levels of catalase and glutathione reductase. NS induced additive significant increase on antioxidant levels in SA injected. GA did not induce any additive increase for examined antioxidant levels. NS decreased total bacterial count increased in SA group more significantly than the effect induced by NS. Conclusion: NS has the potential to control the degree of inflammation at the protein and gene levels of examined cytokines (T-helper1/T-helper2) and antioxidants compared to the effect induced by GA.

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“…The 60 rats were divided into six groups (10 rats/group) with five rats per cage. The control group was fed a normal diet; the camel milk group was administered with a dose of 100 ml camel milk per six rats, based on a previous study (19); the E. coli group was intraperitoneally injected with a virulent strain of E. coli at a dose of 2x10 10 CFU/ml/rat (20); the E. coli + camel milk group was administered with E. coli, as in the E. coli group following camel milk supplementation; the S. aureus group was intraperitoneally injected with a virulent strain of S. aureus at a dose of 1x10 9 CFU/ml/rat (21); and the S. aureus + camel milk group was treated in the same way as the S. aureus group, following prior camel milk supplementation. The rats in the E. coli or S. aureus + camel milk groups were pre-administered with camel milk for 2 weeks prior to pathogen injection.…”

Section: Inoculation Of E Coli and S Aureus Strains Into Rats And Ementioning

confidence: 99%

Protective effects of camel milk against pathogenicity induced by Escherichia coli and Staphylococcus aureus in Wistar rats

Soliman

Hassan

Mostafa

et al. 2012

Molecular Medicine Reports

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Abstract. The aim of the present study was to investigate the protective effects of camel milk on hepatic pathogenicity induced by experimental infection with Escherichia (E. coli) and Staphylococcus aureus (S. aureus) in Wistar rats. The rats were divided into six groups: The control and camel milk groups received water and camel milk, respectively; two groups received camel milk for 2 weeks prior to intraperitoneal injection of either E. coli or S. aureus; and two groups were injected intraperitoneally with E. coli and S. aureus, respectively. All animals were maintained under observation for 7 days prior to biochemical and gene expression analyses. The rats treated with camel milk alone exhibited no changes in expression levels of glutamic-pyruvate transaminase (GPT) or glutamic-oxaloacetic transaminase (GOT), compared with the water-treated group. The E. coli-and S. aureus-injected rats exhibited a significant increase in oxidative stress, and prior treatment with camel milk normalized the observed changes in the expression levels of GPT, GOT and malondialdehyde (MDA). Treatment with camel milk decreased the total bacterial count in liver tissue samples obtained from the rats injected with E. coli and S. aureus. Camel milk administration increased the expression levels of glutathione-S-transferase and superoxide dismutase, which were downregulated following E. coli and S. aureus injection. In addition, camel milk downregulated the increased expression of interleukin-6 and apoptosis-associated genes. Of note, administration of camel milk alone increased the expression levels of the B cell lymphoma 2-associated X protein and survivin anti-apoptotic genes, and supplementation prior to the injection of E. coli and S. aureus induced further upregulation, In conclusion, camel milk exerted protective effects against E. coli and S. aureus pathogenicity, by modulating the extent of lipid peroxidation, together with the antioxidant defense system, immune cytokines, apoptosis and the expression of anti-apoptotic genes in the liver of Wistar rats.

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LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria

Cited by 138 publications

References 39 publications

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU

Effect of gum arabic and Nigella sativa on T-helper1 and T-helper2 immune response in Wistar rats infected with methicillin-resistant Staphylococcus aureus

Protective effects of camel milk against pathogenicity induced by Escherichia coli and Staphylococcus aureus in Wistar rats

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