Anna Gómez

Increased oxidation of certain glycolysis and energy metabolism enzymes in the frontal cortex in Lewy body diseases.

Lipoxidative damage of aldolase A, enolase 1, and glyceraldehyde dehydrogenase (GAPDH) was found in the frontal cortex in a percentage of aged controls by bidimensional gel electrophoresis, Western blot test, in‐gel digestion, and mass spectrometry. Aldolase A and enolase 1 were altered in 12 of 19 cases, whereas oxidation of GAPDH was found in 6 of 19 controls. The three enzymes were oxidized in the frontal cortex in the majority of cases of incidental Parkinsons disease (iPD), PD, and dementia with Lewy bodies (DLB). Differences were statistically significant (χ2 test) for GAPDH in PD and DLB. Densitometric studies have shown that the ratio of oxidized protein per spot is higher in iPD, PD, and DLB compared with controls. These findings show oxidation of three enzymes linked with glycolysis and energy metabolism in the adult human brain as well as increased oxidation of aldolase A, enolase 1, and GAPDH in the frontal cortex in Lewy body diseases. Modifications of these enzymes may result in decreased activity and may partly account for impaired metabolism and function of the frontal lobe in PD.

Involvement of the cerebral cortex in Parkinson disease linked with G2019S LRRK2 mutation without cognitive impairment

Previous studies have shown altered synuclein, increased oxidative stress damage and increased oxidative stress responses in patients with sporadic Parkinson’s disease (PD) without cognitive impairment. Yet no information exists about possible molecular alterations in the cerebral cortex in familial PD. The present study shows abnormal α-synuclein solubility and aggregation, and aggregated nitrated α-synuclein, in the cerebral cortex (area 8) in cases with long-lasting PD linked with the G2019S LRRK2 mutation, one of them with a few Lewy bodies (LBs) and the other two without LBs in the cerebral cortex. Increased expression of the oxidative stress marker malondialdehyde-lysine (MDAL), together with increased oxidative stress responses, AGE receptors (RAGE) and superoxide dismutase 2, occurred in the frontal cortex in the three LRRK2 cases compared with three controls processed in parallel. Bi-dimensional gel electrophoresis, western blotting, in-gel digestion and mass spectrometry disclosed glial fibrillary acidic protein as a target of MDAL adducts. Tubulin β4 and enolase 2 were also identified as targets of oxidative damage. These results demonstrate biochemical abnormalities of α-synuclein, and increased oxidative stress damage and oxidative stress responses in the frontal cortex in PD linked with G2019S LRRK2 mutation not related with the presence of cortical LBs and in the absence of apparent cognitive deficits. These findings show that the cerebral cortex in familial PD linked with G2019S LRRK2 is affected in a similar way than that seen in sporadic PD without cognitive impairment.

Factors associated with delayed postsurgical voiding interval in ambulatory spinal anesthesia patients: a prospective cohort study in 3 types of surgery

BACKGROUND Spinal anesthesia has been considered inappropriate for ambulatory surgery patients because of concern about voiding dysfunction. The purpose of this study was to analyze the relationship between voiding interval and type of surgery under spinal anesthesia with lidocaine and to identify other nonanesthetic risk factors for delayed voiding. PATIENTS AND METHODS A prospective study of 406 patients undergoing to ambulatory surgery under spinal anesthesia with lidocaine was performed. Voiding interval was defined as the time in minutes from the injection of local anesthetic to the patients first spontaneous voiding. Univariate and multivariate linear regression models were constructed to identify risk factors associated with length of voiding interval. RESULTS A total of 187 patients underwent herniorrhaphy; 187 patients underwent lower limb surgery; and 32 patients went benign anorectal surgery. The mean +/- sd voiding interval was 230 +/- 50.5 minutes. Factors associated with length of voiding interval in the univariate analysis were sex, body mass index (BMI), type and duration of surgery, lidocaine dose, and volume of fluid administered. Factors that remained significant in the multivariate model were sex, BMI, lidocaine dose and type of surgery: spontaneous voiding came later after inguinal herniorrhaphy surgery than after lower-limb surgery (regression coefficient 20 minutes; 95% confidence interval 11.5-29.8). Multivariate models performed for each type of surgery separately identified sex and lidocaine dose as factors related to length of voiding interval in all types of surgery. CONCLUSIONS A longer voiding interval was associated with inguinal herniorrhaphy, spinal lidocaine dose, and male sex.