Caffeine and the kidney: what evidence right now?

Caffeine, or 1, 3, 7-trimethylxanthine, is one of the most frequently consumed active drugs worldwide. Its main mechanisms of action include inhibiting the phosphodiesteratic enzyme and adenosine receptors and activating the ryanodine receptors with several actions on all organs. What effect does caffeine have on the kidney? Is caffeine beneficial or dangerous? A review of the current literature reveals conflicting opinions regarding the prolithiasic effect of this substance, whereas its diuretic action is least disputed and more easily observed. Caffeine may have a toxic or preventive effect in some physiologic or pathologic conditions. Some of these incongruences may depend on several factors, such as dosage, prior chronic exposure, genetic-enzymatic axes, and concomitant drug consumption. While awaiting further insight from forthcoming studies on the issue, we may reach a preliminary conclusion that, as yet, there is no evidence contraindicating the consumption of the equivalent of 3 to 4 cups of coffee per day in healthy or nephropathic subjects. However, particular attention should be paid to the elderly, children, and patients on concomitant treatment with analgesics or diuretics, whereas in subjects with a family or clinical history of calcium lithiasis a moderate caffeine consumption should be associated with an adequate fluid intake. Further in-depth studies are required to investigate whether this beverage is beneficial to patients on hemodialysis.     

Brief report: Violent false memories and engagement in aggressive and delinquent behavior: An investigation in adolescents

The present study investigates the relationship between violent false memories and delinquent and aggressive behavior in a sample of adolescents. Two hundred eleven participants completed measures of aggressive and delinquent behavior and performed a modified version of the Deese-Roediger-McDermott (DRM) paradigm, a false memory task for lists of associated words. Participants were presented with a list of ambiguously violent words and three lists of neutral words. For each list a free recall task was performed. Violent false memories were significantly associated with delinquent behaviors in both genders, whereas a significant correlation with aggressive behaviors was found only in males. A multilevel multiple regression showed that the prediction of delinquent behaviors was improved by entering violent false memories into the model as a further predictor, whereas no effect was found for aggressive behaviors. These findings indicate a significant association of violent false memories with delinquent behavior in adolescents.     

Drawing and identifying objects in relation to semantic category and handedness

We investigated whether the directionality of different objects and participants' handedness affected drawing and visual object identification performance. In Experiment 1, 190 participants were asked to draw 246 pictures of objects belonging to different semantic categories. Results showed a preferential direction (leftward, rightward, or frontal view) for most of pictures. In Experiment 2, the directionality patterns found in Experiment 1 were verified in a visual identification task. Sixty participants were requested to identify pictures presented leftward or rightward. For some categories, the speed of responses was greater for pictures having the directionality assessed in the previous experiment. The effect of handedness emerged for two categories of objects (animals and vehicles) characterised by two properties: asymmetry and motion. Findings were discussed in relation to the Motor Image Theory on the isomorphism between motor (drawing) and visual (identification) processes.     

Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia

beta-Thalassemia and sickle cell disease both display a great deal of phenotypic heterogeneity, despite being generally thought of as simple Mendelian diseases. The reasons for this are not well understood, although the level of fetal hemoglobin (HbF) is one well characterized ameliorating factor in both of these conditions. To better understand the genetic basis of this heterogeneity, we carried out genome-wide scans with 362,129 common SNPs on 4,305 Sardinians to look for genetic linkage and association with HbF levels, as well as other red blood cell-related traits. Among major variants affecting HbF levels, SNP rs11886868 in the BCL11A gene was strongly associated with this trait (P < 10(-35)). The C allele frequency was significantly higher in Sardinian individuals with elevated HbF levels, detected by screening for beta-thalassemia, and patients with attenuated forms of beta-thalassemia vs. those with thalassemia major. We also show that the same BCL11A variant is strongly associated with HbF levels in a large cohort of sickle cell patients. These results indicate that BCL11A variants, by modulating HbF levels, act as an important ameliorating factor of the beta-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders. We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for beta-thalassemia and sickle cell anemia.     

Cerebral astroblastoma: analysis of six cases and critical review of treatment options

Astroblastoma is one of the rarest tumors of the central nervous system (CNS), and its classification, histogenesis, diagnosis and therapeutic management are still being debated. The typical histopathological appearance is the perivascular, astroblastic pseudorosette, which is however present in other CNS tumors. To clarify the clinical, radiological, histopathological, prognostic and therapeutic characteristics, which have been treated only recently and are not well established yet due to the rarity of this tumor, six cases of histologically proven astroblastoma were retrospectively analyzed in light of more pertinent literature and paying special attention to therapeutic remarks. Between 1996 and 2005, six patients with cerebral astroblastoma were surgically treated at the Department of Neurosciences—Neurosurgery of Sapienza University in Rome. In three cases the lesion was termed low-grade astroblastoma, and high grade in the other three, according to current standard parameters. Median age of the six patients was 36 years. The time to diagnosis ranged from 1 week to 18 months. The radiological and anatomopathological features of this lesion are described. Surgical removal was total in four cases and subtotal in two. All patients received radiotherapy: two also had chemotherapy with temozolomide (TMZ). The three patients with low-grade astroblastoma are still alive today after a follow-up of 2, 5 and 19 years, respectively. Of the three patients with high-grade lesions, one is still alive after a 7-year follow-up, while the other two survived for 17 months (progression time 15 months) and 35 months (progression-reoperation time 23 months), respectively. Conclusions radical surgical resection is the treatment of choice for astroblastomas. Radiotherapy may play an adjuvant role in the treatment of high-grade lesions. The role of chemotherapy is still very debatable. We propose an aggressive standardized treatment for those lesions that meet anaplastic criteria, owing to their postulated glial origin and the propensity to have aggressive courses, and we advocate the use of a safe adjuvant chemotherapeutic regimen with TMZ, used concomitantly and subsequently to radiotherapy, especially for the high-grade astroblastoma cases. Multicenter studies, taking into account molecular biological findings, are necessary to define a common therapeutic strategy for astroblastomas.     

Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association

We report a 7-year-old girl with 22q13 deletion syndrome, 46,XX,Ish del(22)(q13.3)(ARSA-; D22S1726), who developed a fulminant autoimmune hepatitis requiring orthotopic liver transplantation. Recently, it has been suggested that the Shank3 gene product, whose deficiency is responsible for the features observed in this syndrome, could play a role in immunological response. Despite an increased incidence of respiratory infections, autoimmune diseases have thus far not been reported in patients with this syndrome. This is the first case of fulminant autoimmune hepatitis associated with the 22q13 deletion syndrome. The possible relationships between immune system dysfunctions peculiar of this syndrome and autoimmune hepatitis are discussed.