Tripodal gold(I) polypyridyl complexes and their Cu+ and Zn2+ heterometallic derivatives. Effects on luminescence

Three gold(I) tripodal complexes containing the tris(2-pyridylmethyl)amine (TPA) ligand coordinated to Au-PR3 moieties (PR3 = 1,3,5-triaza-7-phosphatricyclo[3.3.1.13.7]decane, PTA (1), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane, DAPTA (2) and triphenylphosphane (3)) were prepared together with a cage-like structure containing triphosphane 1,1,1-tris(diphenylphosphinomethyl)ethane (4). The luminescence of these complexes has been studied and they show a red shift upon the formation of heterometallic complexes by reaction with Zn(NO3)2, CuCl and [Cu(CH3CN)4]BF4. The different coordination motifs of the Zn2+ and Cu+ heterometallic species and the resulting changes in the recorded absorption, emission and NMR spectra were analysed and supported by TD-DFT calculations

c-Jun N-terminal kinase signaling pathway in excitotoxic cell death following kainic acid-induced status epilepticus.

Systemic injections of kainic acid (KA) cause epileptic seizures with delayed neuronal damage in the limbic system, particularly in the hippocampus. KA excitotoxicity activates complex signal transduction events that trigger apoptotic cell death. The c-Jun N-terminal kinase (JNK) pathway plays an important role in cell death, and the peptide D-JNKI1, a competitive JNK inhibitor, is a potent neuroprotective agent. To analyse the role of JNK and the effects of D-JNKI1 administration on excitotoxic neuronal death, we induced epileptic seizures by intraperitoneal (i.p.) injection of KA in adult male Sprague-Dawley rats; a group of rats received i.p. D-JNKI1 2 h after KA. KA caused massive cell death in the hippocampus: in Nissl-stained sections, stereological counts showed a significant decrease in neuronal density in all CA fields, both at 1 and 5 days after seizures, which was partially prevented by D-JNKI1 treatment. These results were confirmed by counts of degenerating neurons in CA3 in FluoroJade B-stained sections. Seizure activity also induced marked gliosis as observed with glial fibrillary acidic protein (GFAP) immunohistochemistry. We also analysed c-Jun activation as a target of JNK and central transcriptional effector in the adult rat brain following KA injection. Phospho-c-Jun immunoreactivity was absent in the hippocampus of untreated animals, whereas strong nuclear neuronal labeling could be observed, starting from 3 h after KA administration, in microtubule-associated protein-2-positive neurons but not in GFAP-positive astrocytes. D-JNKI1 treatment also reduced the positivity for phospho-c-Jun in the hippocampus, thus confirming the specificity of the peptide in blocking JNK. Therefore, JNK is a promising target for blocking seizure-induced cell death

c-Jun N-terminal kinase signaling pathway in excitotoxic cell death following kainic acid-induced status epilepticus

Systemic injections of kainic acid (KA) cause epileptic seizures with delayed neuronal damage in the limbic system, particularly in the hippocampus. KA excitotoxicity activates complex signal transduction events that trigger apoptotic cell death. The c-Jun N-terminal kinase (JNK) pathway plays an important role in cell death, and the peptide D-JNKI1, a competitive JNK inhibitor, is a potent neuroprotective agent. To analyse the role of JNK and the effects of D-JNKI1 administration on excitotoxic neuronal death, we induced epileptic seizures by intraperitoneal (i.p.) injection of KA in adult male Sprague-Dawley rats; a group of rats received i.p. D-JNKI1 2 h after KA. KA caused massive cell death in the hippocampus: in Nissl-stained sections, stereological counts showed a significant decrease in neuronal density in all CA fields, both at 1 and 5 days after seizures, which was partially prevented by D-JNKI1 treatment. These results were confirmed by counts of degenerating neurons in CA3 in FluoroJade B-stained sections. Seizure activity also induced marked gliosis as observed with glial fibrillary acidic protein (GFAP) immunohistochemistry. We also analysed c-Jun activation as a target of JNK and central transcriptional effector in the adult rat brain following KA injection. Phospho-c-Jun immunoreactivity was absent in the hippocampus of untreated animals, whereas strong nuclear neuronal labeling could be observed, starting from 3 h after KA administration, in microtubule-associated protein-2-positive neurons but not in GFAP-positive astrocytes. D-JNKI1 treatment also reduced the positivity for phospho-c-Jun in the hippocampus, thus confirming the specificity of the peptide in blocking JNK. Therefore, JNK is a promising target for blocking seizure-induced cell death

Neuroprotection by DJNKI1 following seizure activity.

Systemic injections of kainic acid (KA) cause epileptic seizures with delayed neuronal damage in the limbic system, particularly in the hippocampus. KA excitotoxicity activates complex signal transduction events that trigger apoptotic cell death. The c-Jun N-terminal kinase (JNK) pathway plays an important role in cell death, and the peptide DJNKI1, a competitive JNK inhibitor, represents a potent neuroprotective agent. To analyze the role of JNK and the effects of DJNKI1 administration on excitotoxic neuronal death we induced epileptic seizures on adult male Sprague-Dawley rats by i.p. injection of KA (15 mg/kg) with or without DJNKI1 i.p. administration, 2h after KA treatment. KA caused massive cell death in the hippocampus, which could be quantified in Cresyl violet stained sections. In fact, stereological counts showed a significant decrease in neuronal density in all CA fields, but not in the dentate gyrus, both at one and five days after seizures, which was partially prevented by DJNKI1 treatment. Evaluation of neuronal degeneration showed that DJNKI1 treatment prevented the appearance of Fluoro-Jade B positive-profiles in all CA fields. Seizure activity also induced marked gliosis as observed with GFAP immunohistochemistry. The peptide reduced the size of damaged area in the entorhinal cortex. We also analyzed c-Jun activation as target of JNK and central trascriptional effector in the adult rat brain following KA injection. Phospho-c-Jun immunoreactivity was absent in the limbic system of untreated animals, but starting from 3h after KA a strong nuclear neuronal labeling was seen in the limbic system. DJNKI1 treatment also reduced positivity for phospho-c-Jun in the hippocampus, thus confirming the specificity of the peptide in blocking JNK. Therefore, JNK is a promising target for blocking seizure-induced cell death. Support: EEC Stressprotect project

Monitoring exercise intensity in diabetes: applicability of "heart rate-index" to estimate oxygen consumption during aerobic and resistance training

PURPOSE: Accurate quantification and monitoring of exercise "dose", described by oxygen consumption (VO2), is necessary for exercise prescription and individualization. However, due to the complexity and elevated cost of direct, gold-standard methods, this is rarely done outside research laboratories. Heart rate-index (HRindex) is a new simple method to estimate VO2 in healthy and clinical populations. We tested the performance of HRindex to estimate VO2 in diabetic patients during aerobic (AT) and isotonic training (IT). METHODS: Data from 12 males (age: 64\u2009\ub1\u20095 years; BMI: 26\u2009\ub1\u200912) with type 2 diabetes were analysed. VO2 and heart rate were measured during one AT and one IT session. Furthermore, VO2 was indirectly estimated based on HRindex. Then, the correspondence between measured and estimated VO2 was evaluated by two-way RM-ANOVA, correlation and Bland-Altman analysis. RESULTS: Estimated average VO2 values during AT (1292\u2009\ub1\u2009366 ml/min) were not different from (p\u2009=\u20090.243) and highly correlated with (r\u2009=\u20090.87, p\u2009<\u20090.001) the measured values (1369\u2009\ub1\u2009417 ml/min), with a small bias and imprecision. Conversely during IT, HRindex overestimated VO2 compared to the actual measures (1048\u2009\ub1\u2009404 vs 667\u2009\ub1\u2009230 ml/min, p\u2009 64\u20090.001) and only a moderate correlation was found between values (r\u2009=\u20090.43, p\u2009 64\u20090.001), with a large bias and imprecision. CONCLUSION: VO2 of aerobic exercises can be accurately estimated in diabetes patients using HRindex. During isotonic exercise, this method is not recommended for monitoring metabolic intensity due to large overestimation and imprecision. In aerobic exercise, HRindex offers a simple and valid alternative to the direct VO2 determination and may favour the applicability of time-resolved measures of exercise "dose"

Clinical and radiological outcome after endovascular abdominal aortic aneurysm repair: comparison of different grafts. preliminary single-center experience.

Endovascular repair (EVAR) represents a useful and validated alternative to conventional surgery in selected patients with abdominal aortic aneurysm (AAA) because it is associated with a significantly lower long-term MA-related mortality. Data regarding a series of 91 patients (88 men, 3 women, median age 71 years, range 65-82 years) is reported. The patients were divided into three groups, according to the type of implanted stent (Endurant, Excluder and Talent). High American Society of Anesthesiologists Physical Status Classification System (ASA) was important in increasing the likelihood of an early complication (p=0.0007), while it did not have any effect on later adverse events, which were more closely related to the size of the aneurysm (p=0.006). As expected, the aneurysm diameter influenced the endoleak incidence (p=0.011), aneurysmal sac expansion (p=0.029), reintervention risk (p=0.0.31) and the success of treatment (p=0.006). A significantly lower tendency for the development of endoleak (p=0.035) and other late complications (p=0.048) was observed in patients with Endurant device. This group seems to be more likely destined to achieve therapeutic success, but the difference was not significant. A borderline significance (p=0.071) with regard to early complications was also recorded. However, the use of this type of device did not affect survival, which was exclusively related to ASA (p=0.040). No other statistically significant differences were found between groups. Since open surgery for elective suprarenal AAA repair is still associated with considerable mortality, EVAR may offer several advantages over open repair surgery, including a less invasive operative procedure, and shortened intensive care unit and hospital stay. The technological improvements of the prosthesis for EVAR will likely reduce complications related to this technique in the near future