The secret life of neutrophils

Researchers from Canada and Brazil have made live films of the movement of neutrophils into injured sites and studied what signals target these cells to specific locations.
Abstract:
Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage. By using spinning disk confocal intravital microscopy, we examined the kinetics and molecular mechanisms of neutrophil recruitment to sites of focal hepatic necrosis in vivo. Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids. Subsequently, generation of an intravascular chemokine gradient directed neutrophil migration through healthy tissue toward foci of damage. Lastly, formyl-peptide signals released from necrotic cells guided neutrophils through nonperfused sinusoids into the injury. Thus, dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation.

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Good news for brazillian children with leukemia

Brazillian researchers from FIOCRUZ and INCA have shown that childhood leukemia's mortality is decreasing in a steady state.
Abstract:
Objective: To analyze trends in childhood leukemia mortality in the state of Rio de Janeiro, Brazil, between 1980 and 2006.
Method: Gender-stratified leukemia mortality data for children aged < 15 years from 1980 to 2006 were retrieved from the Brazilian Mortality Information System for the state of Rio de Janeiro. Data were stratified by place of death (city of Rio de Janeiro proper, the state capital; Rio de Janeiro Metropolitan Region, excluding the capital; and rest of the state). Leukemia deaths were defined according to death certificate ICD-9 and ICD-10 coding (for deaths occurring in 1980-1995 and 1996-2006, respectively). Leukemia mortality rates were calculated by age and calendar year and age-adjusted to a standard world population. Polynomial linear regression with a 5% significance level was used to evaluate mortality trends in the study regions.
Results: The three studied regions revealed similar trends, with a continuous downward pattern; the most substantial decline was detected in the municipality of Rio de Janeiro (city proper). In all studied areas, leukemia mortality was highest among males.
Conclusion: A downward trend in childhood leukemia mortality was detected throughout the state of Rio de Janeiro. The most pronounced reduction occurred in the state capital.

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Salbutamol for Multiple Sclerosis

Scientists from Harvard, NIH and Chicago's Northwestern University reported the results of a clinical trial that found albuterol is effective for the treatment of multiple sclerosis patients.
Abstract:
Background  Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a β2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy.
Objectives  To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment.
Design  Single-center double-masked clinical trial.
Setting  Academic research.
Patients  Subjects with relapsing-remitting multiple sclerosis.
Main Outcome Measures  In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon at each study time point. The classification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol.
Results  Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P = .005) and 12-month (P = .04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P = .03). Immunologically, IL-13 and interferon- production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P < .05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment.
Conclusion  Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis.
Trial Registration  clinicaltrials.gov Identifier: NCT00039988

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The tau of Alzheimer

Scientists from UCLA and Stanford show tau protein role in the development of Alzheimer's disease.
Abstract:
Amyloid-β (Aβ) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer’s disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of Aβ and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. Aβ oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects.
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