Hemolytic effects of water-soluble fullerene derivatives

A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our model. A validation of these experimental observations has been performed by theoretical studies in which hydrophilic and hydrophobic surface areas were correlated quantitatively with hemolytic properties.     

Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas

Point mutations of the BRAF gene have been recently described with high prevalence in papillary thyroid carcinomas. However, this molecular alteration has not been studied in radiation-induced thyroid tumors. We analyzed the prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post-Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas. Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF mutations and 20% RET/PTC rearrangements. These results demonstrate a significant difference in the molecular genetic profile of sporadic and radiation-induced thyroid tumors.     

Somatostatin in the brain of the cave salamander, Hydromantes genei (Amphibia, Plethodontidae): immunohistochemical localization and biochemical characterization

The distribution of somatostatin-like immunoreactivity in the brain of the cave salamander Hydromantes genei (Amphibia, Plethodontidae) was investigated by using two distinct antisera raised against somatostatin-14. Most somatostatin-positive cells were detected in the ependymal cell layer surrounding the ventricles. These cells possessed the typical morphological characteristics of tanycytes or radial glial cells. Double-labeling with an antiserum against somatostatin and a monoclonal antibody against glial fibrillary acidic protein showed that somatostatin-immunoreactive cells lining the ventricles also exhibited GFAP-like immunoreactivity. Injection of the neurotracer biocytin into the lateral ventricle revealed that neurons lining the ventricles did not contain somatostatin-like immunoreactivity. In the telencephalon, somatostatin-like immunoreactivity was confined to radial glial cells. In the diencephalon, in addition to somatostatin-immunoreactive cells in the ependyma, positive cell bodies were also found in the periventricular preoptic nucleus, the infundibular nucleus, the epiphysis, and the subcommissural organ. In the metencephalon, positive cell bodies were found in the auricula cerebelli, whereas in the rhombencephalon numerous somatostatin-immunoreactive cells were seen lining the ventricular cavity. Immunoreactive nerve fibers were observed in the hypothalamus-median eminence complex. In the pituitary, a discrete group of somatostatin-positive cells was found in the pars distalis. High-performance liquid chromatography analysis of brain extracts revealed that the immunoreactive material coeluted with somatostatin-14. The present results show that the somatostatin peptidergic system in the brain of the cave salamander has a more simple organization than those described in the brain of frog and other vertebrates. This feature is probably related to the expression of high pedomorphic characters in plethodontids. The distribution of somatostatin-like immunoreactivity suggests that, in the cave salamander, somatostatin may act as a neurotransmitter and/or neuromodulator, a central regulator of fluid homeostasis, and a hypophysiotropic neurohormone.     

Language switching mechanisms in simultaneous interpreters: an ERP study

Recent event-related potential (ERP) and neuroimaging studies suggest that bilingual individuals are able to inhibit the processing of a non-target language while speaking or reading in another language. The neural mechanisms subserving code switching still remain matter of debate. The aim of the present study was to shed some light on the neurofunctional bases of such mechanisms. ERPs were recorded in native Italian simultaneous interpreters and monolingual controls during a semantic processing task in which the subjects had to evaluate the sensibleness of final words of incomplete sentences. All participants were strictly right-handed. Interpreters knew at least four languages (from four to eight) at a professional level, from among 11 European and Asian languages, and had an excellent command of English (L2). Four hundred short sentences were presented visually; half of them had an unexpected final word, producing a semantic incongruence. Sentences could be entirely in Italian or in English (unmixed); alternatively, the body of the sentence could be in English and the final word in Italian or vice versa (mixed). ERPs were time locked to the onset of the final word. Both reaction times (RTs) and electrophysiological data indicated a lesser degree of hemispheric lateralization for linguistic function during L2 rather than L1 processing in interpreters. The first effect of lexical switching and code switching was recorded in the time window between 140 and 200 ms at left anterior sites. At N400 level, ERPs were significantly larger to L2 than to L1 words only in the mixed and not in the unmixed condition. No effect of language was observed in the unmixed condition, thus suggesting that the difference in L1/L2 processing was not related to a difference in proficiency, but rather to a different functional organization of semantic integration systems due to the later age of acquisition of L2 compared to L1. Interpreters were faster at reading and comprehending sentences in English ending with an Italian word than vice versa (L2 --> L1 switch).     

Non-invasive diagnostic and functional evaluation of cardiac and pulmonary involvement in systemic sclerosis

BACKGROUND: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value. PATIENTS AND METHODS: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated. RESULTS: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis. CONCLUSION: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.     

Immunomodulating effect of antimicrobial agents on cytokine production by human polymorphonuclear neutrophils

It has been previously demonstrated that some antimicrobial agents enhance activities of human polymorphonuclear neutrophils (PMNs). The effect on the release of cytokines in an inflammatory context from PMNs by these antibiotics was evaluated. We studied the effect of the release of some cytokines by human PMNs RT-PCR analysis on a clinical strain of Klebsiella pneumoniae by comparing the effect with that observed in the presence of co-amoxiclav, sanfetrinem, clarithromycin, prulifloxacin and tobramycin. All the drugs tested were capable of modulating PMN synthesis in vitro of pro-inflammatory cytokines IL-8, IL-1beta, TNF-alpha and IL-6, but not that of anti-inflammatory cytokine IL-10. The degree of their stimulatory or inhibitory potency varied with the cytokine examined.     

Synthesis and in vitro inhibitory activity on human platelet aggregation of novel properly substituted 4-(1-piperazinyl)coumarins

Pursuing our chemical and biological studies in this field, we described the multistep preparation of the new 5-, 6-, or 7-alkoxy and 7-alkoxy-8-methyl substituted 4-(1-piperazinyl)coumarins 5d-v, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca(2+) ionophore A23187. Compounds 5h-j,p,r-u showed notably high activity towards all the platelet aggregation inducers used, and the most active one, 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin (5t), proved to be a potent in vitro antiplatelet agent.     

Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy

BACKGROUND: Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy. METHODS: Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study. RESULTS: Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups. CONCLUSIONS: Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.