Prolonged traumatic coma caused by diffuse axonal lesions]

A 22-year old male patient was admitted for deep coma probably of traumatic origin. There was neither fracture of the skull nor expansive intracranial lesion. The patient survived for 6 years and 8 months without any change in consciousness. Post-mortem neuropathological examination showed lesions which predominated in the white matter and had features that were compatible with diffuse axonal injury. The mechanism responsible for these lesions seems to be stretching and shearing of axones at the moment of impact. The exceptionally long duration of survival probably accounts for the severity of the lesions observed.     

Somatic and psychomotor development of children after hypothermic open-heart surgery

One hundred and seven patients with ventricular septal defect who survived one and a half to thirteen years after hypothermic open-heart surgery were reviewed with respect to somatic, intellectual, and psychomotor development. There were no negative effects associated with deep hypothermic arrest in any of these areas. Abnormal electroencephalograms were seen in one-half the number of patients examined, but there was no close relation between the circulatory arrest period and electroencephalographic findings. CT scanning of the brain indicated that the abnormality decreased with the lapse of the time after hypothermic open-heart surgery. It would appear that hypothermic open-heart surgery with limited circulatory arrest is a useful method, providing that the circulatory arrest is not allowed to exceed a limited period. However electroencephalographic assessment suggests that postoperative cerebral abnormalities may occur more frequently than previously suspected, despite the lack of preoperative abnormalities on the electroencephalograms.     

No evidence of association between apolipoprotein E gene regulatory region polymorphism and Alzheimer's disease in Japanese

The reported association between -491 A/T polymorphism in the regulatory region of the apolipoprotein E gene (APOE) and increased risk for Alzheimer's disease (AD) is controversial: Studies of different racial and ethnic populations have found both positive and negative associations. Examination of -491 A/T polymorphism in 216 patients with sporadic AD and 157 age- and gender-matched controls from the Japanese population revealed that, in contrast to findings for Caucasian populations, the -491 T allele, but not the A allele, was significantly more prevalent in patients with AD than in controls. This difference disappeared when the subjects were stratified by the gene dose of the APOE epsilon4 allele. Moreover, logistic regression analysis, controlling for age, sex, and the presence of the APOE epsilon4 allele, showed no association between the -491 polymorphism and AD. These results suggest that -491 polymorphism does not independently confer susceptibility to AD, but that this polymorphism is in partial linkage disequilibrium with the APOE epsilon2/3/4 polymorphism.     

Characterization of the effects of pancreatic polypeptide in the regulation of energy balance

BACKGROUND & AIMS: Pancreatic polypeptide (PP) belongs to a family of peptides including neuropeptide Y and peptide YY. We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP. METHODS: We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally. Peptide gene expression was also examined in PP-overexpressing mice. Vagal and sympathetic nerve activities were recorded after intravenous administration in rats. Effects of repeated administrations of PP on energy balance and on glucose and lipid metabolism were examined in both ob/ob obese mice and fatty liver Shionogi (FLS)-ob/ob obese mice. RESULTS: Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure. The mechanism involved modification of expression of feeding-regulatory peptides (decrease in orexigenic neuropeptide Y, orexin, and ghrelin along with an increase in anorexigenic urocortin) and activity of the vagovagal or vagosympathetic reflex arc. PP reduced leptin in white adipose tissue and corticotropin-releasing factor gene expression. The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice. Repeated administrations of PP decreased body weight gain and ameliorated insulin resistance and hyperlipidemia in both ob/ob obese mice and FLS-ob/ob obese mice. Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP. CONCLUSIONS: These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin.     

Thrombolytic effects of a novel modified tissue plasminogen activator, E6010, on coronary thrombosis in the pig.

This study was conducted to compare the thrombolytic effect of a novel modified tissue plasminogen activator, E6010, with that of recombinant human tissue plasminogen activator (t-PA), administered by single intravenous bolus injection in pigs with occlusive coronary thrombosis. Thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex coronary artery. Coronary blood flow velocity and hemodynamic parameters were observed for 1 hr after complete cessation of coronary flow. Ten minutes after heparin injection (300 U/kg), E6010, t-PA or placebo was intravenously administered as a bolus. E6010 at 0.2 and 0.4 mg/kg caused recanalization of the occluded coronary artery in 1 of 6 and 5 of 5 pigs, respectively. The time to recanalization after 0.4 mg/kg of E6010 was 22 +/- 11 min (mean +/- S.E.M.). t-PA (0.4 mg/kg) caused recanalization in only 1 of 5 pigs. Recanalization did not occur in any of the 6 animals administered placebo. Plasma clearance of E6010 was smaller than that of t-PA (4.9 +/- 0.3 vs. 9.4 +/- 3.8 ml/min/kg). There were no significant differences in plasma levels of fibrinogen, alpha 2-plasmin inhibitor and plasminogen among the placebo, E6010 and t-PA groups. These results suggest that the slower clearance of E6010 from plasma contributes to the effective thrombolytic action of E6010 following single intravenous bolus injection.     

Redox levels of intravenously administered [14C]coenzyme Q10 and coenzyme Q10-reducing activity in subcellular fractions of guinea pig liver

The blood level of [14C]coenzyme Q10 and the redox levels of [14C]coenzyme Q10 in the liver and heart were measured after intravenous injection of [14C]coenzyme Q10 solubilized in multilamellar liposomes into guinea pigs. The blood level of radioactivity declined biexponentially with half-lives of 11.5 min and 15.6 h in the first and second phases, respectively. The levels of reduced [14C]coenzyme Q10 in the liver and heart reached 55.8 and 46.4%, respectively, of the labeled compound in the tissues at 30 min after the injection. Coenzyme Q10-reducing activity in cytosol, microsomes and mitochondria was also investigated. This activity was found in all the fractions. The total activity was the highest in the liver cytosol. Moreover, the results of experiments using a purified enzyme suggested that one of the coenzyme Q10-reducing enzymes was NAD(P)H: quinone oxidoreductase [EC 1.6.99.2, DT-diaphorase]. These results are discussed in relation to the protective effect of reduced coenzyme Q10 against lipid peroxidation in membranes.     

Brain-derived neurotrophic factor gene polymorphisms and Alzheimer’s disease

Summary. Several lines of evidence have made brain-derived neurotrophic factor (BDNF) an important candidate gene conferring risk for Alzheimers disease (AD). Recently, three studies reported an association between two single-nucleotide polymorphisms (SNP) – i.e., C270T and G196A – in the BDNF gene and AD. This attempt to confirm these associations in a larger AD sample included examination of the linkage disequilibrium of these two SNPs. Comparison of 487 Japanese AD subjects with 471 cognitively normal elderly controls showed higher frequencies of the G allele (60.5 vs. 55.5%, p=0.028) and of both the GG and GA genotypes (85.8 vs. 79.8%, p=0.025) of the G196A polymorphism in AD subjects than in controls and higher frequency of the T allele of the C270T polymorphism in AD subjects who were negative for apolipotrotein E4 (2.0 vs. 4.4%, p=0.035) or positive for AD family history (2.8 vs. 7.1%, p=0.046). These findings suggest that BDNF gene polymorphisms play some role in the development of AD.