Urokinase gene transfer augments angiogenesis in ischemic skeletal and myocardial muscle.

Urokinase plasminogen activator (uPA) is required for both endogenous and vascular endothelial growth factor (VEGF)-augmented angiogenesis in normal tissues, leading us to hypothesize that uPA augmentation by gene transfer might promote angiogenesis in ischemic tissues. Overexpression of uPA was studied in rat myocardial infarction (MI) and mouse hind limb ischemia models and compared with VEGF overexpression effects. Animals were divided into control and three experimental groups (n = 6), receiving intramuscular injections of plasmids as follows: (i) control (empty vector or expressing beta-galactosidase); (ii) uPA; (iii) VEGF(165); (iv) a 1:1 mixture of uPA and VEGF(165). The capillary densities in both ischemic models were greater (P < 0.05) in tissues treated with uPA, VEGF, or a combination of both than in controls. Infarct size was reduced in hearts from uPA and VEGF experimental groups compared with controls (P < 0.05). Local overexpression of uPA induced a marked increase in the number of macrophages and myofibroblasts present within infarcts. Hind limb blood flow was greater in all experimental groups by day 10 (P < 0.05). Overall, the effects of uPA and VEGF were uniformly comparable. Additional analysis revealed association of local edema with VEGF but not with uPA treatment. This study established that uPA gene therapy effectively induces functionally significant angiogenesis in models of acute MI and hind limb ischemia.     

The effects of normal ageing on neuropsychological functioning following traumatic brain injury

Increasing age is associated with greater absolute neuropsychological impairment (e.g. slower process ing speed, diminished memory , although it is unclear if older individuals with traumatic brain injury (TBI) show greater relative impairment than younger individuals with TBI. The current study evaluated the effects of normal ageing on TBI by using age based normative data to calculate indices of relative decline from pre morbid levels (expressed as z-deficit scores) for different age groups (20-39 years, 40-59 years, 60+ years). The sample included 279 individuals with TBI between the ages of 20 and 65 who were assessed in a department of rehabilitation neuropsychology laboratory over a 4-year period. Spearman correlations and ANOVAs did not show-age related differences in relative memory, attention or speed of processing abilities, although results did indicate that increasing age is associated with relatively less impairment in intelligence. The results suggest that the greater neuropsychological impairment noted in older individuals with TBI is most likely related to normal ageing. The importance of considering both absolute and relative degrees of impairment is discussed.     

White matter density in patients with schizophrenia, bipolar disorder and their unaffected relatives.

BACKGROUND: This study sought to assess white matter density in patients and relatives with histories of bipolar disorder and/or schizophrenia. METHODS: Subjects included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives of the three patient groups were also recruited. Subjects underwent an MRI brain scan which was analyzed using a white-matter optimized technique. RESULTS: Subjects with schizophrenia and bipolar disorder showed reduced white matter density in the anterior limb of the internal capsule which was not found in unaffected relatives. Reductions were found in frontal subgyral white matter density in affected subjects with a family history of schizophrenia only. CONCLUSIONS: Abnormal anterior internal capsule white matter may provide a structural substrate for both disorders.     

Association between the serotonin transporter gene and alcohol consumption in social drinkers.

Relatively few studies have investigated the role of the 5HTT gene in intermediate phenotypes such as alcohol consumption in non-alcohol dependent populations. A recent study reported an association with alcohol consumption in a student population. We attempted to replicate these findings and extend on this work in a representative, ethnically homogenous, non-alcohol dependent sample of social drinkers in the United Kingdom. The short allele of the 5HTT gene was significantly associated with increased alcohol consumption (P = 0.03). There was suggestive evidence of a genotype-sex interaction (P = 0.04). Post-hoc tests indicated higher alcohol consumption in men with one or more copies of the short allele, while in women consumption was highest among heterozygotes compared to both homozygote groups. Age at time of data collection and cigarette consumption were entered as covariates. These results replicate recent previous findings and suggest a possibility that this association may differ in men and women.