Prevalence of hepatic hemangioma in patients with focal nodular hyperplasia: MR imaging analysis

PURPOSE: To evaluate the prevalence of hepatic hemangioma in a large population of patients with focal nodular hyperplasia (FNH) and to determine if the prevalence is higher than that in patients with other hepatic masses. MATERIALS AND METHODS: Over a period of 40 months, 247 patients with one or more hepatic masses underwent magnetic resonance (MR) imaging at our institution and met the inclusion criteria for this study. One hundred forty-eight patients received a diagnosis of FNH (study group). Ninety-nine patients had a lesion other than FNH and had no history of chronic liver disease (control group). Imaging findings of the main lesion and presence of associated hemangioma were investigated. chi2 analysis was used to determine if there was a statistically significant difference in the two groups regarding the number of patients with associated masses. RESULTS: Twenty-nine of 148 patients (20%) in the study group had FNH with one or more associated hepatic hemangiomas. Among the 99 patients in the control group, nine (9%) had an associated hemangioma. The prevalence of hemangioma was significantly higher (P <.02) in the study group than in the control group. The prevalence of hemangioma in patients with a solitary FNH lesion compared with that in patients with multiple FNH lesions was not significantly different. CONCLUSION: Patients with FNH are more likely to have an associated hepatic hemangioma than are those with another type of focal hepatic mass.     

Habitual physical activity in children and adolescents during school and free days

PURPOSE: The purpose of this study was to analyze habitual physical activity (HPA) of boys and girls from primary school to high school. METHODS: One hundred eighty-two schoolchildren and teenagers (6-20 yr) were studied at primary school (PS, N= 64), junior high school (JHS, N= 67), and senior high school (SHS, N= 51). HR was continuously monitored during the whole week to assess HPA during school days and free days. Total physical activity (TPA), low physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) were evaluated from the time spent each day above 50%HR reserve (HRR), below 50%HRR, between 50% and 70%HRR, and above 70%HRR, respectively. RESULTS: During school days, TPA decreased by 69% in male subjects (P< 0.05) and by 36% in female subjects (N= 0.058) from PS to SHS. In contrast, TPA did not vary significantly during free days (male subjects, PS: 62 +/- 37 min x d, SHS: 63 +/- 67 min x d; female subjects, PS: 75 +/- 59 min x d, SHS: 62 +/- 44 min x d ). Gender differences were only observed during school days at PS for TPA (male subjects: 121 +/- 37 min x d vs female subjects: 92 +/- 44 min x d, P< 0.05) and VPA (male subjects: 38 +/- 21 min x d vs female subjects: 18 +/- 12 min x d, P< 0.05). Male and female subjects were more inactive during free days than during school days at PS (P< 0.05). No effect of the type of day and gender was observed for all indices of HPA at high schools. CONCLUSIONS: Our results highlight the importance of taking into account the type of day (school day vs free day) in the analysis of children and adolescents' HPA.     

Modulation of P-glycoprotein-mediated multidrug resistance by flavonoid derivatives and analogues

Flavonoid derivatives were synthesized and tested for their ability to modulate P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) in vitro. These compounds belong to various flavonoid subclasses, namely: chromones, azaisoflavones, and aurones. Among the investigated compounds, three showed potent reversing activity. 2-(4-methylpiperazin-1-ylcarbonyl)-5-hydroxychromone (4a), 5,7-dimethoxy-3-phenyl-4-quinolone (5), and 4,6-dimethoxyaurone (6) potentiated daunorubicin cytotoxicity on resistant K562 cells. They were also able to increase the intracellular accumulation of rhodamine-123, a fluorescent molecule which acts as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. The most active compound, 5-hydroxy-2-(4-methylpiperazin-1-ylcarbonyl)chromone (4a) was found to be a powerful reversal agent, more potent than cyclosporin A, used as the reference molecule. No effect was observed on MRP transport nor on cell proliferation. Little apoptosis was induced on K562S cells with 4a compared to K562R, probably due to the extrusion of the compound by Pgp.     

Pituitary adenylate cyclase-activating polypeptide prevents C2-ceramide-induced apoptosis of cerebellar granule cells

The sphingolipid metabolites, ceramides, are critical mediators of the cellular stress response and play an important role in the control of programmed cell death. In particular, ceramides have been shown to induce apoptosis of cerebellar granule cells. We show that pituitary adenylate cyclase-activating polypeptide (PACAP) prevents C2-ceramide-induced apoptosis. The neuroprotective effect of PACAP was dose-dependent and blocked by its antagonist, PACAP6-38, whereas the PACAP-related peptide VIP was inactive. The effect of PACAP on cell survival was mimicked by dibutyryl-cAMP (dbcAMP) and forskolin and prevented by the MEK inhibitor U0126, indicating that both the adenylyl-cyclase and MAP-kinase pathways contribute to the neuroprotective action of the peptide. C2-ceramide and PACAP induced opposite effects on phosphorylated forms of ERK and JNK without affecting the total amounts of ERK and JNK, suggesting that a balance between these two MAP-kinases is critical for the cell survival/death decision. The effect of PACAP on ERK phosphorylation was blocked by U0126, but was not affected by H89 or chelerythrine indicating that PACAP activates ERK through a PKA- and PKC-independent mechanism. C2-ceramide induced a time-dependent activation of caspase-3, enhanced the amount of cleaved caspase-3 and stimulated the DNA fragmentation process, while PACAP strongly inhibited the C2-ceramide-induced activation of caspase-3, reduced the expression of cleaved caspase-3 and blocked DNA fragmentation. Taken together, the present results show that C2-ceramide induces apoptosis of cerebellar granule cells through a mechanism involving activation of caspase-3. Our data also demonstrate that PACAP is a potent inhibitor of C2-ceramide-induced apoptosis.     

How much phenotypic variation can be attributed to parkin genotype?

To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations.     

Fetal and neonatal exposure to the mycotoxin zearalenone induces phenotypic alterations in adult rat mammary gland

Zearalenone is a mycotoxin that is widespread in cereal food. We questioned whether this mycotoxin, administered during known critical exposure periods such as the fetal period and the first days of life, at doses compatible with mean daily intake in humans, could have an effect on mammary gland development in rodents. Wistar female rats were exposed to zearalenone (0.2 μg/kg to 5 mg/kg) during the last 14 days of fetal life and the first 5 post-natal days (PND). The mammary tissue was examined for development and maturation by morphologic analyses and immunochemistry. At PND 30, the mean length of terminal buds was significantly enhanced in all of the zearalenone-exposed females (p < 0.05). The mammary tissue, as evaluated by scoring of tissue slides, was significantly more differentiated in the 1 mg/kg treated group than in controls (p < 0.05). At PND 180, mammary tissue was more differentiated in all of the zearalenone treated groups (p < 0.05). At six months, 4 of 18 females exposed to 5 mg/kg of zearalenone presented mammary hyperplasia lesions. The induction of phenotypic alterations by zearalenone administered in utero and in the neonatal period at doses as low as 0.2 μg/kg suggests that zearalenone could contribute to the induction of breast endocrine disorders.