It is known that host cells can produce type I IFNs (IFN-αβ) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-αβ signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-αβR or IFN-β died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-αβR deficiency was marked, with mortality surpassing that seen in IFN-γR-deficient mice. Animals lacking both IFN-αβR and IFN-γR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-αβ was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-αβ signaling, a marked reduction in macrophage production of IFN-γ, NO, and TNF-α was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-αβ in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.

MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. Recent evidence indicates that miRNAs can function both as tumor suppressors and as oncogenes. It has been demonstrated that in glioblastoma multiforme miR-21 and 221 are upregulated whereas miR-128 and 181 are downregulated. Expression of miR-21, 221, 128a, 128b, 128c, 181a, 181b, 181c was studied using real-time quantitative reverse transcriptase polymerase chain reaction and northern blotting for human astrocytic tumors with different grade of malignancy. miR-21 and 221 were overexpressed in glioma samples, whereas miRNA 181b was downregulated compared with normal brain tissue. miRNA-21 was hyperexpressed in all tumor samples whereas higher levels of miRNA-221 were found in high-grade gliomas. This study is the first analysis of miRNAs in astrocytic tumor at different stages of malignancy. The different expression pattern observed in tumors at different stages of malignancy is probably dependent on the cell-specific repertoire of target genes of tumors sharing different molecular pathways activity and suggests miRNAs may have also a place in diagnosis and staging of brain tumors.

We investigated here the potential role of Toll-like receptors (TLR) and the adaptor protein MyD88 in innate immunity responses to Cryptococcus neoformans, a pathogenic encapsulated yeast. Peritoneal macrophages from MyD88 -/-or TLR2 -/-mice released significantly less TNF-a, compared with wild-type controls, after in vitro stimulation with whole yeasts. In contrast, no differences in TNF-a release were noted between macrophages from C3H/HeJ mice, which have a loss of function mutation in TLR4, relative to C3H/HeN controls. When MyD88-or TLR2-deficient mice were infected with low doses of the H99 serotype A strain, all of the control animals, but none of MyD88 -/-and only 38% of the TLR2 -/-animals survived, in association with higher fungal burden in the mutant mice. Both MyD88 -/-and TLR2 -/-animals showed decreased TNF-a, IL12p40 and/or IFN-c expression in various organs during infection. No difference in susceptibility to experimental cryptococcosis was found between C3H/HeJ mice and C3H/HeN controls. In conclusion, our data indicate that TLR2 and MyD88, but not TLR4, critically contribute to anti-cryptococcal defenses through the induction of increased TNF-a, IL-12 and IFN-c expression.

Study design: Definitive and unequivocal evidence to support the practice of early or late surgery is still lacking in clinical studies. Accordingly, meta-analysis is one of the few methods that offer a rational, statistical approach to management decision. A review of the clinical literature on spinal cord injury with emphasis on the role of early surgical decompression and a meta-analysis of results was performed. Objectives: To determine whether neurological outcome is improved in traumatic spinal cordinjured patients who had surgery within 24 h as compared with those who had late surgery or conservative treatment. Methods: A Medline search covering the period 1966-2000, supplemented with manual search, was used to locate studies containing information on indication, rationale and timing of surgical decompression after spinal cord injuries. The analysis included a total of 1687 eligible patients. Results: Statistically, early decompression resulted in better outcome compared with both conservative (Po0.001) and late management (Po0.001). Nevertheless, analysis of homogeneity showed that only data regarding patients with incomplete neurological deficits who had early surgery were reliable. Conclusions: Although statistically the percentage of patients with incomplete neurological deficits improving after early decompression appear 89.7% (95% confidence interval: 83.9, 95.5%), to be better than with the other modes of treatment when taking into consideration the material available for analysis and the various other factors including clinical limitations; early surgical decompression can only be considered as practice option for all groups of patients.

Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 (n ‫؍‬ 8), control; group 2 (n ‫؍‬ 8), control plus placebo; group 3 (n ‫؍‬ 8), control plus r-Hu-EPO; group 4 (n ‫؍‬ 8), SAH; group 5 (n ‫؍‬ 8), SAH plus placebo; group 6 (n ‫؍‬ 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units͞kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations (P < 0.001), and reduced vasoconstriction of the basilar artery (P < 0.05), ischemic neuronal damage (P < 0.001), and subsequent neurological deterioration (P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.