Positive inversion of extensional footwalls in the southern Serra do Espinhaço, Brazil--insights from sandbox laboratory experiments

Analogue experiments were carried out to get insights into the processes governing positive inversion during the foreland propagating thrust tectonics in the southern Serra do Espinha?o, a Brasiliano/Panafrican foldthrust belt in southeast Brazil. In particular, model listric half-grabens were inverted by applying contractional displacement to the footwall blocks. We investigated two different inversion conditions in listric half-grabens: (i) extensional and contractional detachments at the same level and (ii) at different positions. The models revealed that the development of a forward-breaking thrust system occurs in the basin synrift deposits, by contractional translation of the extensional footwall block when the extensional and contractional master faults do not coincide. Our experiments show the tectonic imbrication between basement and synrift sequences which characterizes the southern Serra do Espinha?o, and support the location in the eastern mountain range domain of the Espinha?o rift master fault system, which is not exposed at the surface.     

Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species

BACKGROUND: The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia-reoxygenation. METHODS: Mature mixed cerebrocortical neuronal-glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase. Extracellular concentrations of glutamate and glutamate uptake were assessed at the end of the ischemic injury by high-performance liquid chromatography and incorporation of L-[H]glutamate into cells, respectively. Free radical generation in cells was assessed 6 h after OGD during the reoxygenation period using 2',7'-dichlorofluorescin diacetate, which reacts with intracellular radicals to be converted to its fluorescent product, 2',7'-dichlorofluorescin, in cell cytosol. RESULTS: Twenty-four hours after OGD, sevoflurane, in a concentration-dependent manner, significantly reduced lactate dehydrogenase release and increased cell viability. At the end of OGD, sevoflurane was able to reduce the OGD-induced decrease in glutamate uptake. This effect was impaired in the presence of threo-3-methyl glutamate, a specific inhibitor of the glial transporter GLT1. Sevoflurane counteracted the increase in extracellular level of glutamate during OGD and the generation of reactive oxygen species during reoxygenation. CONCLUSION: Sevoflurane had a neuroprotective effect in this in vitro model of ischemia-reoxygenation. This beneficial effect may be explained, at least in part, by sevoflurane-induced antiexcitotoxic properties during OGD, probably depending on GLT1, and by sevoflurane-induced decrease of reactive oxygen species generation during reoxygenation.     

Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism

BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. METHODS: Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). RESULTS: Serum Ca levels significantly decreased from 2.75+/-0.15 to 2.59+/-0.10, 2.42+/-0.29 and 2.44+/-0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171+/-102 to 134+/-63 pg/ml by two months (P<0.05) and stabilized thereafter (148+/-99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8+/-18.6 and 51.3+/-19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. CONCLUSION: Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.     

Role of laparoscopy in blunt liver trauma

Although much has been written about the role of laparoscopy in the acute setting for victims of blunt and penetrating trauma, little has been published on delayed laparoscopy relating specifically to complications of conservative management of liver trauma. There has been a shift towards managing liver trauma conservatively, with haemodynamic instability being the key indication for emergency laparotomy, rather than computed tomography findings. However, as a side-effect of more liver injuries being treated non-operatively, bile leak from a disrupted biliary tree presenting later in admission has appeared as a new problem to manage. We describe in this article three cases that have been managed by laparoscopy and drainage alone, outlining the advantages of this technique and defining a new role for delayed laparoscopy in blunt liver trauma.     

Left ventricular diastolic function in hemodialysis patients: role of preload increase maneuver on tissue Doppler imaging evaluation

OBJECTIVE: Tissue Doppler imaging (TDI) has recently been proposed as a relatively preload-independent method to evaluate left ventricular diastolic function. We sought to investigate the higher-accuracy of TDI to assess diastolic function in end-stage renal disease (ESRD) patients on hemodialysis (HD) associated with a preload increase maneuver. METHODS: Thirty-two consecutiveESRD patients (16 female, ages 48.8 +/- 17.5 years, 14 45 years old) were evaluated. Measurements of E, A velocities and the E/A ratio from transmitral inflow pulsed wave Doppler, and E', A' velocities and the E'/A' ratio from TDI were obtained 1 h before and 1 h after HD at baseline and with a preload increase maneuver. RESULTS: The E/A ratio changed significantly in all patients aged >45 before and after HD with the preload increase maneuver. The E'/A' ratio increased in all subjects with the preload increase maneuver before HD but did not change with the maneuver after HD in the euvolemic state in all patients. Conclusion: In ESRD patients on routine HD, TDI evaluation associated with a preload increase maneuver proved to be a more accurate method to identify diastolic dysfunction when the evaluation is performed in euvolemic patients after HD.     

EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families

One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.