Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C-type lectin receptors

Humans are constantly exposed to fungi, either in the form of commensals at epithelial barriers or as inhaled spores. Innate immune cells play a pivotal role in maintaining commensal relationships and preventing skin, mucosal, or systemic fungal infections due to the expression of pattern recognition receptors that recognize fungal cell wall components and modulate both their activation status and the ensuing adaptive immune response. Commensal fungi also play a critical role in the modulation of homeostasis and disease susceptibility at epithelial barriers. This review will outline cellular and molecular mechanisms of anti-fungal innate immunity focusing on C-type lectin receptors and their relevance in the context of host-fungi interactions at skin and mucosal surfaces in murine experimental models as well as patients susceptible to fungal infections.     

Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis

OBJECTIVE: To determine whether additional physiotherapy increases botulinum toxin type A effects in reducing spasticity in patients with multiple sclerosis. DESIGN: A single-blind, randomized, controlled pilot trial with a 12-week study period. SUBJECTS: Thirty-eight patients with progressive multiple sclerosis affected by focal spasticity and who were observed at the Multiple Sclerosis Centre operating in the S. Andrea Hospital in Rome. INTERVENTIONS: For intervention all patients received botulinum toxin type A; the treatment group also received additional physiotherapy to optimize management through passive or active exercise and stretching regimens. MAIN MEASURES: To measure objective and subjective level of spasticity, patients were assessed at baseline, 2, 4 and 12 weeks post treatment by Modified Ashworth Scale and visual analogue scale. RESULTS: When compared with the control group, we found a significant decrease of spasticity by Modified Ashworth Scale (P < 0.01 by t-test) in the treatment group at week 2 (2.73 versus 3.22), week 4 (2.64 versus 3.33) and week 12 (2.68 versus 3.33). The mean (%) difference in Modified Ashworth Scale score between baseline and the end of follow-up was -0.95 (26.1) in the treatment group and -0.28 (7.7) in the control group (P < 0.01). The combined treatment proved also to be more effective by visual analogue scale (P < 0.01) at week 4 (6.95 versus 5.50) and at week 12 (7.86 versus 6.56) but not at week 2 (5.18 versus 5.50; P = 0.41). CONCLUSIONS: Our data suggest that physiotherapy in combination with botulinum toxin type A injection can improve overall response to botulinum toxin.     

Disability assessment using Google Maps

Neurological Sciences - To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and...     

Exit strategies for “needle fatigue” in multiple sclerosis: a propensity score-matched comparison study

Journal of Neurology - Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called “needle fatigue”, i.e., a waning commitment to continue with the...     

Antibiotics attenuate experimental hypertension in rats

Hypertension was produced in Sprague-Dawley rats by intramuscular injections of either corticosterone or ACTH. Lower increases in blood pressure to these challenges were observed in Sprague-Dawley rats pretreated with neomycin or vancomycin which alone had no effect on blood pressure or growth. The development of high blood pressure in spontaneously hypertensive rats of a stroke-prone substrain was also attenuated by oral administration of neomycin. These results suggest that experimental hypertension can be modulated by the administration of antibiotics.     

Association of iota-like toxin and Clostridium spiroforme with both spontaneous and antibiotic-associated diarrhea and colitis in rabbits.

A helically coiled, anaerobic, gram-positive sporeforming bacillus, identified as Clostridium spiroforme, was isolated from the cecal contents of all of 27 rabbits with spontaneous diarrhea, at a mean concentration of 10(6.0) spores per g of material. All of these rabbits also had a toxin present in their cecal contents that was neutralized by anti-Clostridium perfringens type E iota toxin, but not by other clostridial antitoxins. In addition, four rabbits with clindamycin-associated colitis were positive for C. spiroforme at a mean concentration of 10(4.5). All of these animals also had iota-like toxin present. Iota-like toxin was not detected in the cecal contents of 72 healthy animals, although C. spiroforme was found in two of these animals at a mean concentration of 10(6.0). C. spiroforme was shown to produce a toxin in vitro that was lethal to mice and caused dermonecrosis in guinea pigs. In all cases, this toxin was neutralized by anti-C. perfringens type E iota toxin.     

Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis.

Faecal samples from 37 patients with cystic fibrosis and 40 control patients at the Brompton Hospital and the London Chest Hospital were examined for the presence of Clostridium difficile. The organism was isolated from 2 (17%) of control patients who were receiving antibiotics and from one (3.6%) of control patients who had no antimicrobial treatment. Thirty two per cent of the patients with cystic fibrosis excreted C difficile, though none of them had diarrhoea. Two of the three isolates from control patients and nine of the 12 isolates from patients with cystic fibrosis produced toxin B (cytotoxin) in vitro. Toxin B was present in the stools of one of the control patients and three of the patients with cystic fibrosis; toxin A (enterotoxin) was not detected in the faeces of the patients with cystic fibrosis. Two cytotoxigenic strains of C difficile isolated from patients with cystic fibrosis were examined in hamsters; both were virulent, and the animals died.     

Immunogenicity and cross-reactivity of the 70-Kda iron-regulated protein of Neisseria meningitidis in man and animals

The immune response to different serogroups and serotypes of N. meningitidis has been examined in acute and convalescent sera from patients with meningococcal diseases. The focus of the study was the c. 70-Kda iron-regulated outer-membrane protein (FeRP-70). FeRP-70 was demonstrated on all strains of different serogroups and serotypes examined by sodium dodecylsulphate-polyacrylamide gel electrophoresis or Western blots of outer-membrane proteins (OMPs). Immunoblotting experiments demonstrated the presence of considerable amounts of anti-FeRP-70 IgG antibodies in the acute and convalescent sera of six patients; the antibodies reacted with homologous and heterologous strains. However, sera from two patients who died of severe meningococcal septicaemia had no antibodies against FeRP-70 or any other OMPs demonstrable by immunoblotting. Absorbed rabbit hyperimmune sera reacted with FeRP-70 of their homologous strains, but, unlike human sera, with only a few of the heterologous strains. We believe that FeRP-70 is strongly immunogenic in vivo, cross-reactive amongst different strains, and that man and animals differ considerably in their response to similar meningococcal antigens. The functional attribution of human antibody response against this protein requires further exploration.