Craniodigital syndrome of Scott: clinical and neuroradiological features of a new case

We report on a girl presenting with mental retardation, craniofacial dysmorphisms, and syndactyly. The child's mother and maternal grandfather presented bilateral syndactyly of toes 2 and 3. These manifestations, falling within the ambit of what has been termed the craniodigital syndromes, were first reported by Scott et al (1971) in 3 brothers.     

Unawareness of motor impairment and emotions in right hemispheric stroke: a preliminary investigation

BACKGROUND: Awareness may lack in some stroke patients who are not capable of evaluating the nature and severity of illness. Thus, unawareness may have different forms such as anosognosia, neglect, and alexithymia or unawareness of emotions. In this study we investigated the relationship among anosognosia, neglect, alexithymia, and cognition. METHODS: Fifty consecutive right stroke inpatients were approached within the first 3 months from the acute event. Anosognosia was measured with the Bisiach scale, alexithymia with the TAS-20 scale and neglect with line crossing, letter cancellation, figure and shape copying, and line bisection tests. A neuropsychological test battery was used to measure different areas of cognition. RESULTS: despite the strong comorbidity rate among the different forms of unawareness, there are patients who suffer from pure forms of these types of lack of awareness. A multivariate logistic regression model evidenced that presence of neglect (OR = 10.3; 95% CI = 1.4-76.3; p = 0.023) and more difficulty in describing feelings (TAS-20 F2 subscore; OR = 1.3; 95% CI = 1.1-1.7; p = 0.014) were the only predictors of anosognosia. In addition, anosognosics with alexithymia performed worst in a frontal task such as the verbal fluency task (p = 0.042) and in the verbal span forward task (p = 0.026) than pure anosognosics. CONCLUSIONS: Anosognosia for motor impairment is strictly associated with a specific form of unawareness of emotions. Future studies have to clarify if frontal cognitive impairment previously described in anosognosics is a manifestation of unawareness of emotions or anosognosia for motor impairment.     

Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in rat hippocampal slices and cerebrospinal fluid

Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced seizure susceptibility induced by kindling is probably attributable to plastic changes in the synaptic efficacy. Adenosine and guanosine act both as important neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal activity. Adenosine and guanosine can be released per se or generated from released nucleotides (ATP, ADP, AMP, GTP, GDP, and GMP) that are metabolized and rapidly converted to adenosine and guanosine. The aim of this study was to evaluate nucleotide hydrolysis by ecto- and soluble nucleotidases (hippocampal slices and CSF, respectively) after PTZ-kindling (stages 3, 4, or 5 seizures) or saline treatment in rats. Additionally, the levels of purines in rat cerebrospinal fluid (CSF), as well as ecto-NTPDases (1, 2, 3, 5, 6 and 8) and ecto- 5'-nucleotidase expression were determined. Ecto-enzyme assays demonstrated that ATP, AMP, GDP, and GMP hydrolysis enhanced when compared with controls. In addition, there was an increase of ADP, GDP, and GMP hydrolysis by soluble nucleotidases in PTZ-kindling rats compared to control group. The HPLC analysis showed a marked increase in PTZ-kindled CSF concentrations of GTP, ADP, and uric acid, but GDP, AMP, and hypoxanthine concentrations were decreased. Such alterations indicate that the modulatory role of purines in CNS could be affected by PTZ-kindling. However, the physiological significance of these findings remains to be elucidated.     

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat: Part 1: Effects on somatic growth, growth hormone-axis activity and bone mass in the offspring

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure.Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.     

Caffeine drinking potentiates cannabinoid transmission in the striatum: Interaction with stress effects

Caffeine, the psychoactive ingredient of coffee and of many soft drinks, is frequently abused by humans especially during stressful live events. The endocannabinoid system is involved in the central effects of many psychoactive compounds and of stress. Whether caffeine alters the cannabinoid system and interferes with stress-induced synaptic alterations is however unknown. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of mice exposed to caffeine in their drinking solution. Chronic caffeine assumption sensitized GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation by exo- and endocannabinoids. Caffeine was conversely unable to affect the sensitivity of cannabinoid receptors modulating glutamate transmission. The synaptic effects of caffeine were slowly reversible after its removal from the drinking solution. Furthermore, although exposure to caffeine for only 24 h did not produce measurable changes of the sensitivity of cannabinoid CB1 receptors, it was able to contrast the down-regulation of CB1 receptor-mediated responses after social defeat stress.Our data suggest that the cannabinoid system is implicated in the psychoactive properties of caffeine and in the ability of caffeine to reduce the pathological consequences of stress.     

High-performance liquid chromatographic/mass spectrometric studies on the susceptibility of heparin species to cleavage by heparanase

Heparanase is an endo-beta-D-glucuronidase that cleaves the heparan sulfate chains of heparan sulfate proteoglycans and is implicated in angiogenesis and metastasis. With the aim of establishing a simple and reliable method for studying the susceptibility of heparin/heparan sulfate oligosaccharides to be cleaved by heparanase, an on-line ion pair reversed-phase high-performance liquid chromatographic/electrospray ionization mass spectrometric method was set up. The method works in the micromolar range of concentration and does not require derivatization of the substrate or of the products. It is based on mass identification of oligosaccharide fragments generated by heparanase and their quantification with reference to an internal heparin disaccharide standard. Substrates were (1) the synthetic pentasaccharides GlcN (NS,6S) - GlcA - GlcN (NS,3S,6S) - IdoA (2S) - GlcN (NS,6S) - OMe (AGA*IA (M)) and GlcN (NS,6S) - GlcA - GlcN (NS,6S) - IdoA (2S) - GlcN (NS,6S) - OMe (AGAIA (M)), corresponding to the heparin/heparan sulfate active site for antithrombin, and to the same sequence devoid of the 3- O-sulfate group in the central glucosamine, respectively; and (2) two natural heparin octasaccharides containing the AGA*IA sequence in different locations along the chain. The two pentasaccharides exhibited a higher susceptibility to heparanase cleavage with respect to the octasaccharides. The commercial availability of AGA*IA (M) makes it an ideal substrate to determine the specific activity of heparanase preparations. The present method could also be used for rapid screening of potential heparanase inhibitors.     

A randomized study on Peg-interferon alfa-2a with or without ribavirin in liver transplant recipients with recurrent hepatitis C

BACKGROUND/AIMS: We performed a randomized trial on pegylated interferon alfa-2a (Peg-IFNalpha) monotherapy vs Peg-IFNalpha and ribavirin in non-cirrhotic liver transplant recipients with recurrent hepatitis C. METHODS: Forty-two patients transplanted for HCV-related cirrhosis 12-96 months earlier were randomized to Peg-IFNalpha monotherapy (180 microg weekly) or Peg-IFNalpha and ribavirin, up to the maximum tolerated dose, for 48 weeks. RESULTS: Early virological response (EVR, i.e., HCV-RNA2 log drop at week 12) occurred in 76% of the monotherapy and 71% of the combination groups, respectively (intention-to treat). Sustained virological response (SVR) occurred in 8 (38%) and 7 (33%) patients, respectively. EVR had a positive predictive value for SVR of 50% and 47%, respectively, and a 100% negative predictive value in both groups. Six drop-outs occurred in the monotherapy (including 3 rejections) and 7 in the combination groups (including one rejection). Peg-INFalpha dose was reduced in 7 and 8 patients, respectively. The average daily dose of ribavirin was 435 mg/day. CONCLUSIONS: Peg-IFNalpha-2a, with or without ribavirin, induces SVR in one-third of transplant recipients with recurrent hepatitis C. Treatment cessation is indicated in patients without EVR. The low SVR rate is mainly due to inability to sustain full doses of antivirals and lack of the booster effect of ribavirin.