Enantioselective construction of imidazolines having vicinal tetra-substituted stereocenters by direct Mannich reaction of α-substituted α-isocyanoacetates with ketimines.

The catalytic Mannich reaction of α-substituted α-isocyanoacetates with ketimines has been investigated. A variety of imidazolines containing congested vicinal tetra-substituted stereocenters were obtained in excellent yields with high diastereo- and enantioselectivity using cinchona alkaloid amide/Ni(ii) and base catalysts.

Effects of low-dose milnacipran on event-related potentials and neuropsychological tests in persons with traumatic brain injury: A preliminary study.

INTRODUCTION: Psychostimulants are among the most commonly used pharmacological agents for countering cognitive dysfunction and/or enhancing rehabilitation in persons with brain injury. It was postulated that milnacipran, a serotonin-norepinephrine reuptake inhibitor, would be effective against cognitive dysfunction in non-depressed persons with brain injury. METHODS: Eighteen patients were recruited with at least moderate disability more than 4 months after a traumatic brain injury (TBI) and they were randomized to an 8-week, placebo-controlled, double-blind trial. Cognitive dysfunction was assessed at baseline with the Trail Making Test, the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wechsler Memory Scale-Revised (WMS-R) and measurement of event-related potentials (ERPs) both before randomization and after an 8-week administration of milnacipran or placebo. RESULTS: N2 and P3 latencies in the milnacipran group were significantly shortened by the intervention. Moreover, the Verbal Intelligence Quotient and Full Intelligence Quotient scores of the WAIS-R and the delayed recall score of the WMS-R were significantly higher than baseline after milnacipran intervention. CONCLUSION: Milnacipran administration improved ERP measures of attention and information processing in non-depressed persons with brain injury and also improved scores on three sub-scales of standard neuropsychological tests of cognitive dysfunction. Therefore, this intervention merits validation by additional, larger studies.

Direct asymmetric Mannich-type reaction of α-isocyanoacetates with ketimines using cinchona alkaloid/copper(II) catalysts.

The enantioselective direct Mannich-type reaction of ketimines with α-isocyanoacetates has been developed. Excellent yields and enantioselectivity were observed for the reaction of various ketimines and α-isocyanoacetates using cinchona alkaloid/Cu(OTf)2 and a base. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. This process offers an efficient route for the synthesis of α,ß-diamino acids.

Did the educational campaign to support persons with cognitive dysfunction encourage them to participate in society in Northern Kyushu, Japan?

PRIMARY OBJECTIVE: To investigate social participation and the administration of the official certificate for cognitive dysfunction in Northern Kyushu, Japan following a government-conducted educational campaign to support persons with cognitive dysfunction. METHODS AND PROCEDURES: A questionnaire was mailed to members of the Brain Injury Association of Northern Kyushu living with traumatic brain injury; the results were compared with those of the first survey conducted in 2002. MAIN OUTCOMES AND RESULTS: This study evaluated 159 individuals (response rate: 72.6%, 135 males and 24 females), whose mean age at time of injury was 28 years. Eighty-two per cent of the participants were living at home; 72% were independent in activities of daily living. Fifty-nine per cent and 33% had certificates of physical and mental disability, respectively, and 37% were engaged in employment or school attendance. The number of participants who had obtained certificates of physical or mental disability and the number of participants who returned to employment or school significantly increased in comparison to the first survey (χ2 test, p < 0.05). CONCLUSIONS: The model project and educational campaign facilitated social participation and increased the acquisition of the official certificate of cognitive dysfunction.

Induction of arginine vasopressin-enhanced green fluorescent protein expression in the locus coeruleus following kainic acid-induced seizures in rats.

Seizure causes autonomic, neuroendocrine and stress responses. We examined the effects of kainic acid (KA)-induced seizures on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) in the locus coeruleus (LC), an area known to contain noradrenergic cells, in AVP-eGFP transgenic male and female rats, with the rationale to identify stressors which induce AVP synthesis in the LC. Subcutaneous (s.c.) administration of KA caused a progressive development of seizure behavior within 24 h. AVP-eGFP fluorescence in the LC was detected 6, 24, and 48 h and 1 week after administration of KA (12 mg/kg). From a nearly undetectable level, it reached a maximum at 48 h after s.c. administration of KA and returned to the basal levels after 2 weeks. AVP-eGFP fluorescence in the LC after s.c. administration of KA was significantly reduced by the pretreatment with MK-801 (nonselective N-methyl-D-aspartate (NMDA) receptor antagonist). In the KA-administered rats, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localized with TH-immuno-reactivity in the LC. These results suggest that the synthesis of AVP-eGFP is potentially up-regulated in noradrenergic neurons in the LC after KA-induced seizures through the activation of NMDA receptors.

Upregulation of arginine vasopressin synthesis in the rat hypothalamus after kainic acid-induced seizures.

We examined the effects of kainic acid (KA)-induced seizures on arginine vasopressin (AVP) gene expression in the paraventricular (PVN) and the supraoptic nuclei (SON) of normal rats using in situ hybridization histochemistry. We also investigated the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene after KA-induced seizures in transgenic rats. AVP heteronuclear (hn) RNA levels in the PVN and the SON were significantly increased at 3h and 24h after subcutaneous (s.c.) administration of KA in normal rats. AVP mRNA levels in the PVN and the SON did not change significantly at 3h, 24h and 1 week after s.c. administration of KA in normal rats. In KA-administered transgenic rats, AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON were significantly stronger compared to vehicle-administered transgenic rats. By pretreatment with MK-801 (nonselective N-methyl-D-aspartate, NMDA, receptor antagonist), AVP-eGFP transgenic rats after administration of KA did not show preconvulsive symptoms or convulsions and AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON of these rats was significantly reduced. These results suggested that KA-induced increases in AVP transcripts and AVP were prevented by MK801 because seizure activity was prevented or reduced.

A workshop report on wheat genome sequencing: International Genome Research on Wheat Consortium.

Sponsored by the National Science Foundation and the U.S. Department of Agriculture, a wheat genome sequencing workshop was held November 10-11, 2003, in Washington, DC. It brought together 63 scientists of diverse research interests and institutions, including 45 from the United States and 18 from a dozen foreign countries (see list of participants at http://www.ksu.edu/igrow). The objectives of the workshop were to discuss the status of wheat genomics, obtain feedback from ongoing genome sequencing projects, and develop strategies for sequencing the wheat genome. The purpose of this report is to convey the information discussed at the workshop and provide the basis for an ongoing dialogue, bringing forth comments and suggestions from the genetics community.