Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury.

Excitotoxicity following cerebral ischemia elicits a molecular cascade, which leads to neuronal death. c-Jun-N-terminal kinase (JNK) has a key role in excitotoxic cell death. We have previously shown that JNK inhibition by a specific cell-permeable peptide significantly reduces infarct size and neuronal death in an in vivo model of cerebral ischemia. However, systemic inhibition of JNK may have detrimental side effects, owing to blockade of its physiological function. Here we designed a new inhibitor peptide (growth arrest and DNA damage-inducible 45ß (GADD45ß-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation. GADD45ß-I was engineered by optimizing the domain of the GADD45ß, able to bind to MKK7, and by linking it to the TAT peptide sequence, to allow penetration of biological membranes. Our data clearly indicate that GADD45ß-I significantly reduces neuronal death in excitotoxicity induced by either N-methyl-D-aspartate exposure or by oxygen-glucose deprivation in vitro. Moreover, GADD45ß-I exerted neuroprotection in vivo in two models of ischemia, obtained by electrocoagulation and by thromboembolic occlusion of the middle cerebral artery (MCAo). Indeed, GADD45ß-I reduced the infarct size when injected 30 min before the lesion in both models. The peptide was also effective when administrated 6 h after lesion, as demonstrated in the electrocoagulation model. The neuroprotective effect of GADD45ß-I is long lasting; in fact, 1 week after MCAo the infarct volume was still reduced by 49%. Targeting MKK7 could represent a new therapeutic strategy for the treatment of ischemia and other pathologies involving MKK7/JNK activation. Moreover, this new inhibitor can be useful to further dissect the physiological and pathological role of the JNK pathway in the brain.

A naphthalene diimide dyad for fluorescence switch-on detection of G-quadruplexes.

A non-fluorescent naphthalene diimide (NDI) dimer, conjugating red and blue NDI dyes, becomes red/NIR emitting upon G-quadruplex binding. The fluorescence lifetime which is significantly different for the complexes, the G-quadruplex/dimer and the weakly emitting ds-DNA/dimer is the key feature for the development of new rationally engineered G-quadruplex sensors.

Subsurface constructed wetlands for wastewater treatment and reuse in agriculture: five years of experiences in Sicily, Italy.

The paper reports the results of an investigation on a H-SSF constructed wetland for tertiary treatment in a small community located in eastern Sicily, Italy. The system is designed to reuse wastewater for the irrigation of olive orchards covering about 150 hectares. From March 2001 to September 2005, wastewater samples were collected and the following chemical-physical parameters were determined according to Standard Methods: temperature, pH, EC, DO, TSS (105degrees C), BOD5, COD, TN, TP. The following microbiological parameters were also evaluated: total coliforms, faecal coliforms, Escherichia coli, faecal streptococci, Salmonella, helminth eggs. Mean removal efficiencies ranged from 77 to 92% (TSS), 37 to 72% (BOD5), 51 to 79% (COD), 97 to 99.5% (E. coli). Removal efficiency of Salmonella and helminth eggs was always 100% in all samples; however, only 150% of total samples matched the limit of E. coli (< 50 CFU/100 mL) fixed by Italian legislation for wastewater reuse.

Transversal fixation of restorations in combination with the Octa abutment of the ITI Dental Implant System.

In aesthetically demanding locations of the dentition, the replacement of a single tooth by means of an oral implant is often difficult because of technical limitations of the abutments systems used. The transversal Fixation System in combination with the Octa abutment of the ITI Dental Implant System presents a novel development to overcome these limitations. The report describes the engineering and design of this technical development.

[Ulcerative plantar lichen. Is it an indicator of an autoimmune disease?]. / Liquen ulceroso plantar. Marcador de enfermedad autoinmune?

A 48 years old female has had erosive and ulcerative lichen planus with sores in both heals, onychodystrophy and typical lesions in oral mucous membranes. Laboratory examination revealed specific abnormalities indicative of autoimmune thyroiditis and primary biliary cirrhosis. This clinical variant of lichen planus was associated with immunological disturbances. Autoimmune diseases must be investigated in patients with erosive and ulcerative lichen planus.