Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study

1. Metabolic syndrome (MS) is one of the greatest public health problems in Mexico, where more than 75% of adults in urban populations are overweight or obese. Metabolic syndrome has several comorbidities, which result in a high cardiometabolic risk. 2. Some of the vasopathogenic phenomena in MS are caused by nitroxidant stress, secondary to cardiometabolic dysfunction. 3. The action of metformin to diminish or control MS remains a matter of debate. 4. In the present study, 60 patients with at least three diagnostic criteria for MS were divided into two groups. Both groups received similar dietary counselling, but one group was given 850 mg metformin daily. 5. The variables assessed were body mass index, waist circumference, systolic and diastolic blood pressures (SBP and DBP, respectively), total cholesterol (TC), high- and low-density lipoprotein-cholesterol, triglycerides (TG), fasting glucose, nitroxidant metabolites (free carbonyls, malondialdehyde, dityrosines and advanced oxidative protein products (AOPP)), nitric oxide (NO), carotid vascular stiffness, carotid intima-media thickness (IMT) and C-reactive protein (CRP). 6. After 1 year follow up, both groups reported weight loss, as well as decreases in waist circumference, SBP and DBP. 7. Patients on metformin exhibited reductions in TC and IMT and there were marked changes in nitroxidation: levels of carbonyls, dityrosines and AOPP were reduced, whereas those of NO were increased, indicating better endothelial function. In addition, in patients given metformin, CRP levels decreased. 8. In conclusion, metformin has a considerable beneficial effect on nitroxidation, endothelial function and IMT in patients with MS.     

Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing

The aim of this study was to compare the response of infants with acute wheezing to treatments with inhaled terbutaline when administered by nebulizer or by metered-dose inhaler and spacer device (MDI-spacer). Thirty-four infants between the ages of 1 and 24 months who were seen in our emergency department for acute wheezing were studied in a double-blind, randomized trial. The participants received two treatments of terbutaline at 20-min intervals, either by a nebulizer (2 mg/dose in 2.8 mL of 0.9% saline solution) or by an MDI-spacer device (0.5 mg/dose). The outcome measure was a clinical score, based on respiratory rate, degree of wheezing, retractions, degree of cyanosis, color, and pulse oximetry data measured before treatment, 20 min after the first treatment, and again 20 min after the second treatment. There was no difference in the rate of improvement in the clinical score between infants who received terbutaline by nebulizer and those who received it by MDI-spacer. We conclude that MDI-spacers and nebulizers are equally effective means of delivering beta-2 agonists to infants and small children with acute wheezing. Pediatr Pulmonol. 1998; 26:344–348. © 1998 Wiley-Liss, Inc.     

β-Amyloid peptide induced cytoskeletal reorganization in cultured astrocytes

The effects of β-amyloid (25–35) (βA) on cultured astrocytes from rat cortex were studied and compared with those of a scrambled peptide and with untreated cultures. Single addition (from 5 to 200 μg/ml) of βA peptide induced a marked morphological change in astrocytes, changing their flat polygonal shape into stellate process-bearing morphology. The changes induced by βA were concentration and time-dependent. The addition of the scrambled peptide did not alter cell viability in comparison with untreated astrocyte cultures. However, cell viability was dose-dependently decreased by βA. A subpopulation of βA-treated astrocytes showed an increase in glial fibrillary acidic protein (GFAP) and Vimentin (Vim) immunostaining while other reactive astrocyte markers such as S100β, MAP2, and ApoE remained unaltered or undetectable. The morphological changes in βA-treated astrocytes appeared to be mainly due to a cytoskeletal reorganization, since the total amounts of GFAP and Vim proteins were not essentially modified. These results strongly suggest that astrocytes are another cellular target of the effects of βA and this may be relevant to understanding the neuropathology of Alzheimer's disease. J. Neurosci. Res. 47:216–223, 1997. © 1997 Wiley-Liss, Inc.     

Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy

Introduction

Our previous studies have shown that amyloid β peptide (Aβ) is subject to complement-mediated clearance from the peripheral circulation, and that this mechanism is deficient in Alzheimer's disease. The mechanism should be enhanced by Aβ antibodies that form immune complexes (ICs) with Aβ, and therefore may be relevant to current Aβ immunotherapy approaches.

Sex differences in the phagocytic and migratory activity of microglia and their impairment by palmitic acid

Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade. In this study, we have determined the effect of palmitic acid in the inflammatory profile, motility, and phagocytosis of primary male and female microglia, both in basal conditions and in the presence of a pro‐inflammatory stimulus (interferon‐γ). Male microglia in vitro showed higher migration than female microglia under basal and stimulated conditions. In contrast, female microglia had higher basal and stimulated phagocytic activity than male microglia. Palmitic acid did not affect basal migration or phagocytosis, but abolished the migration and phagocytic activity of male and female microglia in response to interferon‐γ. These findings extend previous observations of sex differences in microglia and suggest that palmitic acid impairs the protective responses of these cells.     

Evidence on impact of community-based environmental management on dengue transmission in Santiago de Cuba

During the dengue outbreak that struck Santiago de Cuba in 2006-2007, we conducted an observational study in the Mariana Grajales district, the former setting of a community trial for Aedes aegypti control. In the trial, community working groups (CWG) had been created in 29 randomly selected intervention house blocks, and routine vector control activities alone were conducted in the remaining 30 control blocks. The CWG elaborated and implemented with the population plans and activities to reduce Aedes infestation. They were still functional in 2006 and continued organizing community-based environmental management activities. The attack rate of dengue fever during the outbreak was 8.5 per 1000 inhabitants in the former intervention blocks and 38.1 per 1000 inhabitants in the control blocks, which corresponds to a relative risk of 4.5 (95% CI 3.1-6.5). There was a significantly higher proportion of unaffected intervention blocks, and affected blocks had on average substantially less cases than affected control blocks. This study indicates that community-based environmental management inserted in the routine A. aegypti control programme can not only sustainably curb vector infestation but also have an impact on dengue transmission.     

Comparative trial of effectiveness of pyrethroid insecticides against peridomestic populations of Triatoma infestans in northwestern Argentina

The effects of different pyrethroid insecticides, formulations, and doses on peridomestic populations of Triatoma infestans (Klug) were evaluated in 128 houses with 148 identified infested peridomestic sites in northwestern Argentina between October 2003 and March 2005. Four treatments were randomly assigned within each community: two doses of 5% suspension concentrate beta-cypermethrin in water applied with manual compression sprayers, the standard dose (S) at 50 mg and a double dose (2S) at 100 mg active ingredient (AI)/m2; and two emulsifiable concentrates diluted in diesel fuel and applied with power sprayers, 25% cypermethrin (100 mg [AI] /m2) (CF) and 10% permethrin (170 mg [AI]/m2) (DF). Infestation was assessed by timed manual collections with a dislodging agent at baseline, 5, 12, and 17 mo postspraying, and the sites found to be reinfested at 5 mo postspraying were selectively resprayed. Only 2S eliminated T. infestans from all peridomestic sites up to 12 mo postspraying, and it was significantly more effective than all other treatments. At 5 mo postspraying, more sites treated with CF or DF rather than S had bug colonies that probably represented residual foci, which they also failed in eliminating after a second spray. At 17 mo postspraying, the prevalence of reinfested peridomestic sites was 5% for 2S, 29% for S, 43% for CF, and 54% for DF. The application of suspension concentrate pyrethroids in dose twice as large as that currently in use in the attack phase produces a greater initial impact and may eliminate peridomestic populations of T. infestans.     

Facilitated "fast track" referral reduces time from abnormal screening mammogram to diagnosis

BACKGROUND: The Screening Mammography Program of British Columbia (SMPBC) implemented voluntary, facilitated referral to diagnostic imaging ("Fast Track") after testing 5 interventions to reduce time from an abnormal screening mammogram to diagnosis. The purpose of this study was to compare time intervals for patients evaluated through the Fast Track process with patients who were not. METHODS: Data were extracted from the SMPBC database for women with abnormal screens conducted from January 1, 2003 to June 30, 2005 (N = 40,292). After exclusions, 39,607 screens were analyzed. Median and 90th percentile times were calculated from abnormal screen to diagnosis and for three subintervals: abnormal screen to notification, notification to first assessment, and first assessment to diagnosis. RESULTS: One third of abnormal screens were investigated through Fast Track imaging facilities. Overall, the median time from abnormal screen to diagnosis was 8 days faster for Fast Track compared with non-Fast Track. There was no clinically significant difference in time from abnormal screen to notification. The median time from notification to first assessment was 1.1 weeks (Fast Track) compared with 2.4 weeks (non-Fast Track), a reduction of 9 days or 54% in the interval targeted by the Fast Track strategy. The time interval distribution from first assessment to diagnosis was significantly different only for those having a core biopsy (average 3 days faster for Fast Track). INTERPRETATION: Facilitated referral to diagnostic imaging reduces average time from notification of abnormal screen to first assessment by more than half. Additional strategies are needed to address diagnostic investigation beyond initial imaging procedures.