Amantadine is a cationic aliphatic primary amine eliminated by the kidneys, excreted predominantly unchanged into the urine, and undergoes limited metabolism. Renal tubule secretion has an important role in its elimination. We studied two aspects of amantadine disposition, firstly acetylation, by developing a model to induce the enzyme spermidine/spermine N1-acetyltransferase (SSAT1) with N1, N11-diethylnorspermine (DENSPM) and alcohol (Alc) as representative agents reported to induce its activity, and secondly renal secretion, by studying the effect of intravenous bicarbonate infusion on its renal elimination. We drew two conclusions, firstly, longer exposure to Alc combined with DENSPM administration provided the greatest potentiation of SSAT1 enzyme activity than each agent alone, which indicates a high likelihood of synergy between Alc and DENSPM; and secondly, bicarbonate load administered to healthy male volunteers impairs amantadine renal secretion in the absence of a clinically important change in blood pH, serum creatinine concentration or urinary creatinine clearance.

Amantadine is a cationic aliphatic primary amine eliminated by the kidneys, excreted predominantly unchanged into the urine, and undergoes limited metabolism. Renal tubule secretion has an important role in its elimination. We studied two aspects of amantadine disposition, firstly acetylation, by developing a model to induce the enzyme spermidine/spermine N1-acetyltransferase (SSAT1) with N1, N11-diethylnorspermine (DENSPM) and alcohol (Alc) as representative agents reported to induce its activity, and secondly renal secretion, by studying the effect of intravenous bicarbonate infusion on its renal elimination. We drew two conclusions, firstly, longer exposure to Alc combined with DENSPM administration provided the greatest potentiation of SSAT1 enzyme activity than each agent alone, which indicates a high likelihood of synergy between Alc and DENSPM; and secondly, bicarbonate load administered to healthy male volunteers impairs amantadine renal secretion in the absence of a clinically important change in blood pH, serum creatinine concentration or urinary creatinine clearance.

Musicians comprise a unique population whereby persistent musical practice involving complex cognitive and motor tasks dates back to childhood when the potential for neural plasticity is at its highest. Accordingly, it has been speculated that musical training results in neural structural and functional differences between musicians and non-musicians. In particular, there is evidence to indicate parietal regions are more equally lateralized in musicians, but research investigating visuospatial abilities and lateralization in musicians is scarce. Studies 1 and 2 aimed to assess the visuospatial ability and cognitive processing speed of adult musicians versus ‪demographically and educationally matched non-musicians. ‪Musicians performed more quickly and more accurately than non-musicians in two tasks of visuospatial ability, and completed more items than non-musicians in three tasks of processing speed, suggesting ‪musicians had better ‪visuospatial ability and a faster speed of processing. Studies 3 and 4 aimed to investigate ‪visuospatial attention in ‪these groups using a line-bisection task and a visual discrimination task. On both tasks musicians demonstrated more balanced visuospatial attention with a slight bias to the right hemispace, which was in contrast to the non-musicians’ bias to the left hemispace, a natural phenomenon known as ‘right pseudoneglect’. In Study 5, the laterality of visual processing in musicians and non-musicians was further investigated by comparing electrophysiological interhemispheric transfer time (IHTT) of lateralized visual stimuli across the corpus callosum. Non-musicians had faster right-to-left than left-to-right IHTT consistent with previous research, whilst musicians had more balanced IHTT in both directions and faster left-to-right transfer than non-musicians. Absolute latency patterns revealed similar results and consistently demonstrated more balanced visual processing in musicians. The behavioural data, analysed in Study 6, revealed a tendency (n.s.) for the ‪musician group to respond more quickly to stimuli presented in the right visual field than to stimuli presented in the left visual field, whilst ‪non-musicians did not show this pattern. Overall, the results indicate that musicians have enhanced visuospatial ability and are less lateralized for visuospatial attention and perception than non-musicians. The results are discussed in relation to plastic developmental changes that may be caused by extended musical training from childhood. Specifically, it is proposed that musical training in early life may elicit a process of myelination that is more bilaterally distributed than myelination in non-musicians.

Musicians comprise a unique population whereby persistent musical practice involving complex cognitive and motor tasks dates back to childhood when the potential for neural plasticity is at its highest. Accordingly, it has been speculated that musical training results in neural structural and functional differences between musicians and non-musicians. In particular, there is evidence to indicate parietal regions are more equally lateralized in musicians, but research investigating visuospatial abilities and lateralization in musicians is scarce. Studies 1 and 2 aimed to assess the visuospatial ability and cognitive processing speed of adult musicians versus ‪demographically and educationally matched non-musicians. ‪Musicians performed more quickly and more accurately than non-musicians in two tasks of visuospatial ability, and completed more items than non-musicians in three tasks of processing speed, suggesting ‪musicians had better ‪visuospatial ability and a faster speed of processing. Studies 3 and 4 aimed to investigate ‪visuospatial attention in ‪these groups using a line-bisection task and a visual discrimination task. On both tasks musicians demonstrated more balanced visuospatial attention with a slight bias to the right hemispace, which was in contrast to the non-musicians’ bias to the left hemispace, a natural phenomenon known as ‘right pseudoneglect’. In Study 5, the laterality of visual processing in musicians and non-musicians was further investigated by comparing electrophysiological interhemispheric transfer time (IHTT) of lateralized visual stimuli across the corpus callosum. Non-musicians had faster right-to-left than left-to-right IHTT consistent with previous research, whilst musicians had more balanced IHTT in both directions and faster left-to-right transfer than non-musicians. Absolute latency patterns revealed similar results and consistently demonstrated more balanced visual processing in musicians. The behavioural data, analysed in Study 6, revealed a tendency (n.s.) for the ‪musician group to respond more quickly to stimuli presented in the right visual field than to stimuli presented in the left visual field, whilst ‪non-musicians did not show this pattern. Overall, the results indicate that musicians have enhanced visuospatial ability and are less lateralized for visuospatial attention and perception than non-musicians. The results are discussed in relation to plastic developmental changes that may be caused by extended musical training from childhood. Specifically, it is proposed that musical training in early life may elicit a process of myelination that is more bilaterally distributed than myelination in non-musicians.

Musicians comprise a unique population whereby persistent musical practice involving complex cognitive and motor tasks dates back to childhood when the potential for neural plasticity is at its highest. Accordingly, it has been speculated that musical training results in neural structural and functional differences between musicians and non-musicians. In particular, there is evidence to indicate parietal regions are more equally lateralized in musicians, but research investigating visuospatial abilities and lateralization in musicians is scarce. Studies 1 and 2 aimed to assess the visuospatial ability and cognitive processing speed of adult musicians versus ‪demographically and educationally matched non-musicians. ‪Musicians performed more quickly and more accurately than non-musicians in two tasks of visuospatial ability, and completed more items than non-musicians in three tasks of processing speed, suggesting ‪musicians had better ‪visuospatial ability and a faster speed of processing. Studies 3 and 4 aimed to investigate ‪visuospatial attention in ‪these groups using a line-bisection task and a visual discrimination task. On both tasks musicians demonstrated more balanced visuospatial attention with a slight bias to the right hemispace, which was in contrast to the non-musicians’ bias to the left hemispace, a natural phenomenon known as ‘right pseudoneglect’. In Study 5, the laterality of visual processing in musicians and non-musicians was further investigated by comparing electrophysiological interhemispheric transfer time (IHTT) of lateralized visual stimuli across the corpus callosum. Non-musicians had faster right-to-left than left-to-right IHTT consistent with previous research, whilst musicians had more balanced IHTT in both directions and faster left-to-right transfer than non-musicians. Absolute latency patterns revealed similar results and consistently demonstrated more balanced visual processing in musicians. The behavioural data, analysed in Study 6, revealed a tendency (n.s.) for the ‪musician group to respond more quickly to stimuli presented in the right visual field than to stimuli presented in the left visual field, whilst ‪non-musicians did not show this pattern. Overall, the results indicate that musicians have enhanced visuospatial ability and are less lateralized for visuospatial attention and perception than non-musicians. The results are discussed in relation to plastic developmental changes that may be caused by extended musical training from childhood. Specifically, it is proposed that musical training in early life may elicit a process of myelination that is more bilaterally distributed than myelination in non-musicians.

Musicians comprise a unique population whereby persistent musical practice involving complex cognitive and motor tasks dates back to childhood when the potential for neural plasticity is at its highest. Accordingly, it has been speculated that musical training results in neural structural and functional differences between musicians and non-musicians. In particular, there is evidence to indicate parietal regions are more equally lateralized in musicians, but research investigating visuospatial abilities and lateralization in musicians is scarce. Studies 1 and 2 aimed to assess the visuospatial ability and cognitive processing speed of adult musicians versus ‪demographically and educationally matched non-musicians. ‪Musicians performed more quickly and more accurately than non-musicians in two tasks of visuospatial ability, and completed more items than non-musicians in three tasks of processing speed, suggesting ‪musicians had better ‪visuospatial ability and a faster speed of processing. Studies 3 and 4 aimed to investigate ‪visuospatial attention in ‪these groups using a line-bisection task and a visual discrimination task. On both tasks musicians demonstrated more balanced visuospatial attention with a slight bias to the right hemispace, which was in contrast to the non-musicians’ bias to the left hemispace, a natural phenomenon known as ‘right pseudoneglect’. In Study 5, the laterality of visual processing in musicians and non-musicians was further investigated by comparing electrophysiological interhemispheric transfer time (IHTT) of lateralized visual stimuli across the corpus callosum. Non-musicians had faster right-to-left than left-to-right IHTT consistent with previous research, whilst musicians had more balanced IHTT in both directions and faster left-to-right transfer than non-musicians. Absolute latency patterns revealed similar results and consistently demonstrated more balanced visual processing in musicians. The behavioural data, analysed in Study 6, revealed a tendency (n.s.) for the ‪musician group to respond more quickly to stimuli presented in the right visual field than to stimuli presented in the left visual field, whilst ‪non-musicians did not show this pattern. Overall, the results indicate that musicians have enhanced visuospatial ability and are less lateralized for visuospatial attention and perception than non-musicians. The results are discussed in relation to plastic developmental changes that may be caused by extended musical training from childhood. Specifically, it is proposed that musical training in early life may elicit a process of myelination that is more bilaterally distributed than myelination in non-musicians.

Musicians comprise a unique population whereby persistent musical practice involving complex cognitive and motor tasks dates back to childhood when the potential for neural plasticity is at its highest. Accordingly, it has been speculated that musical training results in neural structural and functional differences between musicians and non-musicians. In particular, there is evidence to indicate parietal regions are more equally lateralized in musicians, but research investigating visuospatial abilities and lateralization in musicians is scarce. Studies 1 and 2 aimed to assess the visuospatial ability and cognitive processing speed of adult musicians versus ‪demographically and educationally matched non-musicians. ‪Musicians performed more quickly and more accurately than non-musicians in two tasks of visuospatial ability, and completed more items than non-musicians in three tasks of processing speed, suggesting ‪musicians had better ‪visuospatial ability and a faster speed of processing. Studies 3 and 4 aimed to investigate ‪visuospatial attention in ‪these groups using a line-bisection task and a visual discrimination task. On both tasks musicians demonstrated more balanced visuospatial attention with a slight bias to the right hemispace, which was in contrast to the non-musicians’ bias to the left hemispace, a natural phenomenon known as ‘right pseudoneglect’. In Study 5, the laterality of visual processing in musicians and non-musicians was further investigated by comparing electrophysiological interhemispheric transfer time (IHTT) of lateralized visual stimuli across the corpus callosum. Non-musicians had faster right-to-left than left-to-right IHTT consistent with previous research, whilst musicians had more balanced IHTT in both directions and faster left-to-right transfer than non-musicians. Absolute latency patterns revealed similar results and consistently demonstrated more balanced visual processing in musicians. The behavioural data, analysed in Study 6, revealed a tendency (n.s.) for the ‪musician group to respond more quickly to stimuli presented in the right visual field than to stimuli presented in the left visual field, whilst ‪non-musicians did not show this pattern. Overall, the results indicate that musicians have enhanced visuospatial ability and are less lateralized for visuospatial attention and perception than non-musicians. The results are discussed in relation to plastic developmental changes that may be caused by extended musical training from childhood. Specifically, it is proposed that musical training in early life may elicit a process of myelination that is more bilaterally distributed than myelination in non-musicians.

Hepatocellular carcinoma (HCC) is one of the most common cancerous diseases worldwide. The annual occurrences exceed one million peoples affected. Currently, the treatment modalities for HCC include surgical resection, trans-arterial embolization (TAE) and chemotherapy. However, these modalities are not completely effective, underscoring the need for development of novel therapeutic approaches. PTEN, a tumor suppressor that antagonizes the PI3K pathway, is frequently mutated or deleted in various human cancers. Loss of PTEN occurs in 40-50% of surgical resected HCC samples and predicts poor prognosis for HCC patients, suggesting PTEN restoration may constitute a treatment alternative for HCC. Since PTEN increased ethanol-induced cytotoxicity in hepatoma cells, PTEN gene delivery may serve as an adjuvant therapy in conjunction with ethanol TAE for HCC. In the present study, we evaluated the efficacy of PTEN gene therapy and its combination with ethanol in a syngenic Novikoff hepatoma model by implantation of N1-S1 cells into livers of Sprague Dawley rats. Adenovirus encoding PTEN (Ad-PTEN) or green fluorescent protein (Ad-GFP) was generated for gene delivery studies. The optimal condition for adenovirus vectors to infect N1-S1 cells was determined at multiplicity of infection (MOI) of 100-200. Infection of N1-S1 cells with Ad-PTEN, but not Ad-GFP, increased PTEN levels and led to 40-50% inhibition of cell proliferation via cell cycle arrest. Besides, the half maximal -inhibitory concentration (IC50) for ethanol in N1-S1 cells was determined at 6%. Combination with PTEN gene delivery further augmented the cytotoxicity of ethanol in N1-S1 cells from 40% to 70% inhibition. To evaluate the prevention efficacy of PTEN gene delivery, N1-S1 cells were infected with adenovirus vectors then implanted into livers of Sprague-Dawley rats to induce Novikoff hepatoma. Injection of PBS- or Ad-GFP-treated N1-S1 cells led to large hepatoma (with an average size of 3-4 cm) with tumor incidence of 80-90%. In contrast, injection of Ad-PTEN-infected N1-S1 cells only induced one hepatoma (with size of 0.1 cm) in six rats, suggesting that pretreatment with PTEN gene delivery effectively abolished the tumorigenic potential of N1-S1 hepatoma cells in vivo. In summary, these results validate the feasibility of PTEN gene delivery as a new promising therapeutic strategy for the treatment of orthotopic hepatoma in immune-competent rats.

The current study used event-related potentials (ERPs) to investigate how motivational salience in the form of expectation violation influences spatial attention. The medial frontal negativity (MFN) ERP indexes expected value, being negative to unexpected punishments and positive to unexpected rewards. The P1 and N1 ERPs index spatial attention, being larger to stimuli in attended locations. This design attached motivational value to locations by making one visual hemifield economically rewarding (greater probability of a rewarding outcome) and the other punishing (greater probability of a punishing outcome). Keypresses to a dot probe following a reward-signifying stimulus were awarded money if correct, and penalized following a punishment-signifying stimulus if incorrect. We predicted that salience would be attached to visual hemifield, thus the MFN would be most negative to punishing outcomes in the rewarding hemifield and most positive to rewarding outcomes in the punishing hemifield. We also predicted that attention would be allocated to a location where expectation was violated, thus the P1 and N1 ERPs would be larger and RTs (reaction times) faster to dot probes appearing in the same side as an outcome that violated expected value. In a sample of 36 participants, there were no significant effects on the MFN, although the means were in the predicted direction, suggesting a lack of power. Contrary to our hypothesis, keypresses were slower, P1 smaller, and N1 larger to probes opposite the location where an expectation violation occurred. This suggested that expectation violation did not direct attention to a particular location, but produced general interference.

Our lives are dominated by a complex visual world, and spatially selective attention allows us to process only the most relevant information. Previous evidence suggests that if possible locations of stimulus presentation are delineated, attention affects processing in a spatially graded manner. This gradient is seen in both behavioral measures and in visual evoked potentials (VEPs). Stimuli presented close to cued regions elicit faster responses and larger VEPs than those presented farther away. However, both position in the visual field and allocation of attention may contribute to the observed gradients. These relative contributions can be distinguished by comparing responses on physically identical trials when attention is directed to locations at various distances from the stimuli. In the current study, participants attended to one of 12 squares arranged in a circle around fixation. Letters appeared individually, each in one of the squares; 80% were O’s (standards) and 20% were X’s (deviants). Participants were instructed to press a button when an X appeared at the attended location. The largest amplitude N1s (150-200 ms) were observed when participants attended to the location where a standard was presented. VEPs elicited by standards showed evidence of asymmetric attentional gradients. Specifically, the gradient of facilitation spread down more than up. Results also showed that attention had differential effects on the stages of processing indexed at specific time windows. These results confirm that attention can be applied to visual processing in a spatial gradient, reveal its asymmetric distribution, and elaborate on the timing of its selectivity.