Plastic reorganization of neural systems for perception of others in the congenitally blind.

Recent evidence suggests that the function of the core system for face perception might extend beyond visual face-perception to a broader role in person perception. To critically test the broader role of core face-system in person perception, we examined the role of the core system during the perception of others in 7 congenitally blind individuals and 15 sighted subjects by measuring their neural responses using fMRI while they listened to voices and performed identity and emotion recognition tasks. We hypothesised that in people who have had no visual experience of faces, core face-system areas may assume a role in the perception of others via voices. Results showed that emotions conveyed by voices can be decoded in homologues of the core face system only in the blind. Moreover, there was a specific enhancement of response to verbal as compared to non-verbal stimuli in bilateral fusiform face areas and the right posterior superior temporal sulcus showing that the core system also assumes some language-related functions in the blind. These results indicate that, in individuals with no history of visual experience, areas of the core system for face perception may assume a role in aspects of voice perception that are relevant to social cognition and perception of others' emotions.

Age-related differences in sleep-dependent consolidation of motor skills in patients with narcolepsy type 1.

OBJECTIVE: The influence of post-training sleep on the consolidation process of procedural (ie, visual and motor) knowledge has shown to be less effective in patients with chronic sleep disorders compared with healthy subjects. To ascertain whether the influence of the altered architecture of sleep in patients with narcolepsy type 1 (ie, with cataplexy: NT1) also varies with age, we compared the performance values of 16 children (aged from nine to 14 years) and 16 adults (aged from 24 to 51 years) on finger tapping task (FTT) after daytime and nighttime periods of sleep in the 24 hours following training. METHODS: All patients, who were drug-free and underwent continuous polysomnographic recordings, could take one or more naps after the training session (at 10 a.m.) until one hour before the first retrieval session (at 6 p.m.) and had an undisturbed period of nighttime sleep from about 10 p.m. to two hours before the second retrieval session (again at 10 a.m.). RESULTS: The pattern of sleep-dependent consolidation was significantly different in the two groups of patients: while performance accuracy was higher in adults compared with children at each session, performance speed improved after daytime sleep in children and after nighttime sleep in adults. The improvement in performance speed, although not related with any sleep parameters in both groups, was positively correlated with the daytime and nighttime total sleep time (TST) in children with greater consolidation gain. CONCLUSION: The interaction between time of day and age in the time course of consolidation of new motor skills discloses a different role of daytime sleep (active in children, simply protective from interferences in adults) in NT1 patients and suggests a flexible use of napping in the educational context.

Urodynamic investigations in patients with spinal cord injury: should the ice water test follow or precede the standard filling cystometry?

OBJECTIVES: To evaluate whether the ice water test (IWT) should be performed before or after the standard urodynamic investigation (UDI). PATIENTS AND METHODS: Two cohorts of patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) were matched by lesion level and age. The patients of cohort A (n=55, retrospective cohort) underwent the IWT before and the patients of cohort B (n=110, prospective cohort) after standard UDI. The IWT effect on urodynamic parameters has been compared between the two groups using the Mann-Whitney U-test for independent samples. UDI was performed according to good urodynamic practices recommended by the International Continence Society. RESULTS: The mean age of both cohorts was 49 years. Performing the IWT before versus after standard UDI resulted in a significantly lower maximum cystometric bladder capacity (P=0.01), lower incidence of detrusor overactivity (P=0.017) and lower maximum detrusor pressure during IWT (P=0.04). All other urodynamic parameters assessed demonstrated no significant difference (P>0.05). CONCLUSIONS: Our results are in line with findings from animal studies demonstrating a bladder cooling-induced gating effect on the micturition reflex volume threshold on the level of sacral interneurons. Since the IWT is an unphysiological investigation that might significantly bias subsequent urodynamics, we suggest that the IWT should not precede more physiological standard UDI.

Dermoscopic yellow structures in basal cell carcinoma.

BACKGROUND: Yellowish structures in dermoscopy comprise milia-like cysts (MLCs) and yellow lobular-like structures. OBJECTIVE: This study aimed at establishing the frequency of these features in BCC and at describing their dermoscopic details. METHODS: A retrospective analysis of digital dermoscopic images referring to 400 BCCs was performed. Images were evaluated for the presence of starry and cloudy MLCs and yellow lobular-like structures. RESULTS: Among the 400 BCCs constituting our database, 40 presented yellowish structures (10%). "Yellow" BCCs were located more frequently on the head and were mainly of the nodular type. MLCs were observed in 7.75% of the cases (with a mean number of 4.9 MLCs per lesion), whereas yellow globules were noticed in 4.2% /ucodep of the lesions. CONCLUSION: In the presence of BCC specific dermoscopic criteria, the observation of MLCs and yellow lobular-like structures should not prompt the dermatologist to exclude the diagnosis of BCC.

Toxicity of cadmium on Sertoli cell functional competence: an in vitro study.

Cadmium (Cd), an ubiquitous environmental metal, mainly used for industrial purposes, may be toxic at level of the reproductive system. Testis tubular-based Sertoli cells (SC), play a major role in constituting the blood-testis barrier and provide a unique microenvironment for the genesis and differentiation of germ cells. Hence SC strictly control sperm qualitative and quantitative parameters. We aimed to assess whether exposure to Cd would adversely affect superior mammal SC viability and function. We isolated and purified SC from pre-pubertal pig testes according to our method and incubated the retrieved cells with three different Cadmium chloride concentrations (5-10-15 microM). Parameters of SC function such as inhibin B and anti-Mullerian hormone (AMH) were depressed by Cd exposure, contrary to what observed in untreated controls. No impairment of the FSH receptor integrity on the SC, as assessed by 17-beta-estradiol production, upon stimulation with FSH, was observed in either 5 microM Cd-treated or untreated controls. Differences, on the contrary, were observed for higher Cd concentrations (10 and 15 mM), in terms of FSH receptor integrity, that was altered, as compared to untreated controls, in terms of lower production of 17-beta-estradiol. In addition, the apoptotic test showed a significant increase of early (ANNEXIN V-/Propidium Iodide+) (AV-/PI+) and late apoptotic cells (AV+/ PI+) in all Cd -treated SC conditions as compared to controls. In conclusion, the Cd -related toxicity on SC, clearly demonstrated by our study, even at low concentrations, is expected to damage spermatogenesis that directly is dependent upon retention of SC viability and function.

Silica particle size and shape: in vitro effects on extracellular matrix metabolism and viability of human bronchial epithelial cells.

Crystal micro-morphology and dimension of silica particles could be responsible for the high prevalence of silicosis as recently found among goldsmiths. In the present study we investigated two samples of silica particles with different surface sizes and shapes for their capacity to induce changes in ECM component production. In addition we investigated if their different effects could be related to cytotoxicity and apoptotic effects. Human bronchial epithelial cells were cultured with or without a sample of Silica used for casting gold jewellery, named in our experiments Silica P or a commercial sample of Silica with different physical and chemical properties, named in our experiments Silica F. After 48 h of exposure PCR analysis determined levels of several matrix components. As induction of the apoptosis cascade, annexin assay, caspase 3 activity and cellular cytoxicity by MTT assay were assayed. Silica F promoted fibronectin, MMP12, tenascin C and Integrins b5 gene expressions more than Silica P. Silica P stimulated more TGFß1 and its TGFßR1 receptor than Silica F. Cytotoxic effects were induced by the two samples of Silica. On the contrary, no alteration in classic apoptotic marker protein expression was observed in presence of either Silica F or Silica P, suggesting silica particles affect ECM production and metalloproteases through a mechanism that does not involve apoptotic activation. Different Silica micromorphology and TGFß signal pathway are linked to lung fibrotic effects but the potential role Silica in apoptotic and toxic reaction remains to be ascertained.

Comparative in vitro studies on the fibrogenic effects of two samples of silica on epithelial bronchial cells.

The small dimension and particle shape of silica in gypsum used to prepare moulds for lost wax casting might be responsible for the high prevalence of silicosis in gold jewellery. To test this hypothesis, human pulmonary epithelial cell (BEAS-2B) cultures were exposed to two samples of silica with different crystal micro-morphologies: Silica Powder (Silica P) which is used in casting gold jewellery, and no powder Silica (Silica F). Extracellular matrix (ECM) production was evaluated using radio-labelled precursors and quantified by RT-PCR analysis. Expression of basic fibroblast growth factor (FGF2) and its receptor (FGFR2) was also evaluated. The results demonstrated Silica P particles had a very fine lamellar crystalline structure while Silica F was characterized by larger rounded crystals. Silica P stimulated collagen production significantly more than Silica F and downregulated laminin and metalloprotease expression. Both silica samples down-regulated FGF2 but only Silica F enhanced FGF2 receptor expression. In conclusion each Silica sample promoted a profibrotic lung microenvironment in a different manner and also elicited different FGF2 signalling pathways. The data confirm that different micromorphology of Silica particles affects the fibrogenic potential and the molecular mechanisms of dust pathogenicity.

A study on the thickness of radicular dentine and cementum in anterior and premolar teeth.

AIM: This study aimed to measure the thickness of radicular dentine and cementum in incisors, canines and premolars, and to develop geometric average models. METHODOLOGY: The roots of 220 extracted human teeth were sectioned in three horizontal parallel planes and measured using an optical microscope. For each cut surface buccal, lingual, mesial, and distal thickness of the root wall was measured. Mean values of the thickness at each location of each cut surface were calculated. The observed differences in thickness by tooth type, location, and section were compared by ANOVA and Student's t-test. RESULTS: Maxillary central incisors and maxillary canines had the greatest widths. In all teeth with a single root, the wall thickness were greater on the lingual side than the buccal side. Although differences between mesial and distal thicknesses were not statistically significant. CONCLUSIONS: Wall thickness varied greatly. The lingual surfaces of roots were larger. All roots had thin walls in the apical third.

trans-Dichlorotetrakis(4-methylpyrimidine-N1)ruthenium(II).

The title compound, trans-[Ru(II)Cl(2)(N(1)-mepym)(4)] (mepym is 4-methylpyrimidine, C(5)H(6)N(2)), obtained from the reaction of trans,cis,cis-[Ru(II)Cl(2)(N(1)-mepym)(2)(SbPh(3))(2)] (Ph is phenyl) with excess mepym in ethanol, has fourfold crystallographic symmetry and has the four pyrimidine bases coordinated through N(1) and arranged in a propeller-like orientation. The Ru-N and Ru-Cl bond distances are 2.082 (2) and 2.400 (4) A, respectively. The methyl group, and the N(3) and Cl atoms are involved in intermolecular C-H...N and C-H...Cl hydrogen-bond interactions.

Structure-activity relationships in 2,2-diphenyl-2-ethylthioacetic acid esters: unexpected agonistic activity in a series of muscarinic antagonists.

As a continuation of previous research on anticholinergic drugs derived from 2,2-diphenyl-2-ethylthioacetic acid, several 5,5-diphenyl-5-ethylthio-2-pentynamines (2-11) were synthetised and their antimuscarinic activity on M(1-4) receptor subtypes was evaluated by functional tests and binding experiments. One of the compounds obtained showed unexpected agonistic activity in functional experiments on M(2) receptors. Since the compound carried a phenylpiperazine moiety, other similar compounds (12-17) were prepared and found to be endowed with similar behaviour. These ligands, although possessing the bulky structure characterising muscarinic antagonists, display agonistic activity at M(2) subtypes while, as expected, behaving as antagonists on M(3) and M(4) subtypes. On M(1) subtypes, they show agonistic activity which, however, is not blocked by atropine. The peculiar pharmacological profile of these compounds is of interest for studying muscarinic receptor subtypes.

Interleukin secretion, proteoglycan and procollagen alpha(1)(I) gene expression in Crouzon fibroblasts treated with basic fibroblast growth factor.

The present study provides the first evidence that fibroblasts obtained from patients affected by Crouzon syndrome, a rare craniosynostosis, despite mutations in the high-affinity bFGF receptor retain their capacity to respond to bFGF. The growth factor reduces IL-1 secretion, downregulates biglycan and procollagen alpha(1)(I), and increases betaglycan expression. Since betaglycan is a co-receptor for bFGF signalling, an alternative signal transduction pathway is suggested in Crouzon fibroblasts, to explain the documented changes in ECM macromolecule production.

Design, synthesis, and preliminary pharmacological evaluation of 1, 4-diazabicyclo[4.3.0]nonan-9-ones as a new class of highly potent nootropic agents.

Several 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones have been synthesized and tested in vivo on mouse passive avoidance test, to evaluate their nootropic activity. The results show that they represent a new class of nootropic drugs with a pharmacological profile very similar to that of piracetam, showing much higher potency with respect to the reference. Among the compounds studied, 7 (DM 232) shows outstanding potency, being active at the dose of 0. 001 mg kg(-1) sc.

TGFbeta isoforms and decorin gene expression are modified in fibroblasts obtained from non-syndromic cleft lip and palate subjects.

Interaction between extracellular matrix (ECM) and cytokines is thought to be crucial for palatal development. The localization of transforming growth factors (TGFalpha and TGFbeta isoforms) in craniofacial tissues suggests that they carry out multiple functions during development. In the present report, we studied TGFalpha, TGFbeta1, and TGFbeta3 expressions and their effects on ECM macromolecule production of normal and cleft palatal fibroblasts in vitro, to investigate the mechanisms by which the phenotypic modulation of fibroblasts occurs during the cleft palate process. The results indicated that, while TGFalpha mRNA was not evidenced in CLP or normal fibroblasts, a reduced TGFbeta1 hybridization signal was detected in CLP fibroblasts. In addition, these secreted more active TGFbeta3 than TGFbeta1, as evaluated in a biological assay. The CLP phenotype, which differed from the normal one because of its higher PG decorin expression and greater production of GAG and collagen, was further modified by the addition of growth factors. In fact, in CLP fibroblasts, TGFalpha and TGFbeta1 down-regulated PG decorin transcript, TGFbeta1 increased collagen and GAG in both cellular and extracellular compartments, and TGFbeta3 promoted secretory processes of cells. In conclusion, the data represent the first report in a human model in vitro that TGFbeta1 and beta3 are differently expressed and are correlated to the CLP phenotype. Thus, strength is given to the hypothesis that TGFbeta isoforms are the potential inducers of phenotypic expression in palatal fibroblasts during development and that an autocrine growth factor production mechanism may be responsible for the phenotypic modifications.

A regulatory role of fibroblast growth factor in the expression of decorin, biglycan, betaglycan and syndecan in osteoblasts from patients with Crouzon's syndrome.

Bone development is controlled by the autocrine and/or paracrine effects of regulatory molecules. We previously showed that the phenotype of fibroblasts obtained from patients affected by Crouzon's syndrome, an autosomal dominant disease characterized by pathological skull bone development, differed from that of normal cells and was regulated by interleukin treatments. The changes in the relative concentrations of extracellular macromolecules (glycosaminoglycans-GAG, collagen and fibronectin) were associated with abnormal interleukin secretion that affected the microenvironment where the osteogenic processes take place. Mutations in human fibroblast growth factor receptors are now thought to be involved in Crouzon's syndrome. Since coactivation of interleukins and basic fibroblast growth factor (bFGF) is probably implicated in morphogenetic and osteogenic processes and heparan sulphate proteoglycans have a critical role in regulating bFGF activity, the phenotypes of normal and Crouzon osteoblasts were studied and the effects of bFGF on the expression of bFGF, procollagen alpha1 (I), and proteoglycan (PG) genes for biglycan, decorin, betaglycan and syndecan analyzed. Specific human cDNA probes were used to screen the relative levels of mRNA by Northern analysis. Spontaneous or bFGF-modulated release of interleukins was also assayed. The bFGF gene transcript was detected only in Crouzon osteoblasts. We showed for the first time that Crouzon osteoblasts, despite a mutation in the FGF receptor, still responded to exogenous bFGE In fact, the growth factor induced changes in the GAG profile and in the levels of mRNA coding for PG and procollagen alpha1 (I) and down-regulated heparan sulfate GAG chains. ELISA showed that bFGF-induced interleukin secretion differed in normal and Crouzon osteoblasts. The observed differences in PG core protein, procollagen alpha1 (I) and bFGF could be associated with the Crouzon bone phenotype and also should provide further understanding on the molecular basis of the diseased state of bone.

Antisense 'knockdowns' of M1 receptors induces transient anterograde amnesia in mice.

The effect on memory processes of inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN) was investigated in the mouse passive avoidance test. Mice received a single intracerebroventricular (i.c.v.) injection of M1 aODN (0.3, 1.0 or 2.0 nmol per injection), degenerated ODN (dODN) or vehicle on days 1, 4 and 7. An amnesic effect, comparable to that produced by antimuscarinic drugs, was observed 12, 24, 48 and 72 h after the last i.c.v. aODN injection, whereas dODN and vehicle, used as controls, did not produce any effect. Reduction in the entrance latency to the dark compartment induced by aODN disappeared 7 days after the end of aODN treatment, which indicates the absence of any irreversible damage or toxicity caused by aODN. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that a decrease in M1 mRNA levels occurred only in the aODN-treated group, being absent in all control groups. Furthermore, a reduction in M1 receptors was observed in the hippocampus of aODN-treated mice. Neither aODN, dODN nor vehicle produced any behavioral impairment of mice. These results indicate that the integrity and functionality of M1 receptors are fundamental in the modulation of memory processes.

Hybridized and isosteric analogues of N1-acetyl-N4-dimethyl-piperazinium iodide (ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (DMPP) with central nicotinic action.

A series of piperazine derivatives, obtained by hybridization of N1-acetyl-N4-dimethyl-piperazinium iodide (1, ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (3, DMPP) or of the corresponding tertiary bases (2, 4) with arecoline (5) and arecolone (6) or by isosteric substitution of the phenyl ring of DMPP, has been synthesized. Hybridization afforded compounds that, both as tertiary bases and as iodomethylates, have no affinity for the nicotinic receptor. On the contrary, isosteric substitution gave compounds that maintain affinity for the receptor; among them, two tertiary bases (37, 38), show affinity in the nanomolar range for the nicotinic receptor. The pharmacological profile of these isomeric compounds is quite interesting as they present differences in their peripheral and central effects, suggesting that they interact with different subtypes of the nicotinic receptor.

Comparative effects of TGFbeta on proliferation of 7- and 14-day-old chick embryo fibroblasts and lack of involvement of the ODC/PA system in the TGFbeta signaling pathway.

The growth regulatory activity of transforming growth factor beta (TGFbeta) on chick embryo skin fibroblasts was compared in two developmental ages, days 7 and 14. The time course of 3H-thymidine incorporation, an S-phase marker of replication, was determined during 36 hr of TGFbeta treatment. Seven-day-old cells showed a prereplicative phase of 6 hr, and 14-day-old cells showed a prereplicative phase of 12 hr. DNA synthesis peaked at 24 hr in 7-day-old fibroblasts and was 10 times higher than that in 14-day-old fibroblasts. Ornithine decarboxylase (ODC) activity and content of the natural polyamines spermine (Spm), spermidine (Spd), and putrescine (Put) differed during cell cycle. ODC activity peaked at 12 hr in 7-day-old cells and at 6 hr in 14-day-old cells. Its level was two times higher at day 7 and was associated with a greater content of ODC mRNA. The maximum of polyamine (PA) concentration was determined after 12 hr of treatment in 7-day-old cells and after 36 hr in 14-day-old cells. These findings indicate that the TGFbeta proliferative response of embryo fibroblasts changes during development and is associated with activation of the ODC/PA system. Cotreatment with alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ODC, did not reduced growth rate. Inhibition of ODC resulted in levels of Put and Spd comparable to that of quiescent fibroblasts, whereas Spm concentration remained higher. Because an altered ODC metabolism does not convey the effects of TGFbeta on DNA synthesis, the ODC/PA system may not play a role in the pathway of TGFbeta signaling.