Coagulation Activation in Children with Sickle Cell Disease Is Associated with Cerebral Small Vessel Vasculopathy

Background

Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state.

Methods

Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications.

Results

SS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec.

Conclusions

SS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts.     

Shoot age as a confounding factor on detecting the effect of human-induced disturbance on Posidonia oceanica growth performance

The response of orthotropic rhizome elongation and primary production of Posidonia oceanica to anthropogenic perturbations and potential confounding effects of shoot age were assessed using a Linear Multilevel Model (LMM). This model examined the confounding effect of age by comparing the estimates of impact and variance components obtained by excluding and including Age as an explanatory variable. Age had a negative effect on rhizome elongation and primary production with an annual decrease of 0.6 mm y^− 1 and 7 mg dw y^− 1 respectively. According to the LMM when age effect was omitted, the differences between disturbed and control locations in rhizome elongation and primary production were 2.62 mm y^− 1 and 0.044 g dw y^− 1 respectively. These effects were statistically not significant. On the contrary, when age effect was included in the statistical model, impacts became evident for both variables, with significant differences between disturbed and control locations of 5.85 mm y^− 1 and 0.081 g dw y^− 1 for rhizome elongation and primary production, respectively. Thus, particular attention should be paid to the potential confounding effect of shoots age in analyses of impacts on growth performance of P. oceanica.     

Emerging and re-emerging viral infections in Europe

Emerging viral infections are becoming a serious problem in Europe in the recent years. This is particularly true for severe acute respiratory syndrome (SARS), West Nile virus (WNV) disease, Toscana virus (TOSV) disease, and potentially for avian influenza virus (H5N1). In contrast, emergence or re-emergence of severe viral infections, including tick borne encephalitis virus, and viral haemorrhagic fever caused by Hantavirus and dengue virus have been frequently reported in several European countries. Laboratory diagnosis of these viral infections based on viral isolation or detection by immune electron microscopy, immunoassay and polymerase chain reaction (PCR) has dramatically improved in the recent years, and SARS represents a good example of a diagnostic approach to emerging viral infections. Finally, old and new promising agents are in the pipeline of pharmaceutical companies to treat emerging viral infections. However only prevention based on large epidemiological studies, and research and development of new vaccines may be able to control and eventually eradicate these deadly viral infections.     

Growth impacts in a changing ocean: insights from two coral reef fishes in an extreme environment

Coral Reefs - Determining the life-history consequences for fishes living in extreme and variable environments will be vital in predicting the likely impacts of ongoing climate change on reef fish...     

Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.     

Short-term effects of coumarin along the maize primary root axis

The short-term effects of coumarin on three different maize primary root zones, transition zone (TZ, 3 mm) and two non-growing zones (NGZ1 and NGZ2 at 20 and 50 mm, respectively), were studied in order to investigate the effect of the allelochemical on maize root elongation rate (RER). The RER, plasma membrane (pm) H⁺-ATPase activity, quantitative pH changes and cell membrane potentials were evaluated. The results showed that coumarin caused at the TZ (1) an increased RER; (2) an enhancement of pm H⁺-ATPase activity and proton extrusion; and (3) a transient depolarization followed by a hyperpolarization of cell membrane potential. These observations were not evident in the NGZ1 and NGZ2 of the maize root. Coumarin-treatment in the NGZ1 did not change RER, but caused a membrane depolarization, while the NGZ2 was mostly insensitive to the allelochemical. These data suggested that the primary maize root was sensitive to coumarin within a 20 mm section from the root tip, but the more distal NGZ2 was not involved in coumarin-elicited physiological responses.Key words: coumarin, membrane potential, pmH⁺-ATPase, proton efflux, root elongation rate     

Effect of different K+ concentrations on cryptococcus neoformans phenoloxidase activity

Melanin synthesis in Cryptococcus neoformans, catalyzed by phenoloxidase activity, is one of the oldest virulence factors known. However, until now, the relationship between melanin production in C. neoformans and its virulence has been poorly understood. Among different chemical compounds only Fe³⁺ and Cu²⁺ cations enhance the phenoloxidase activity in C. neoformans. A few reports in the literature describe the influence of different cations on C. neoformans phenoloxidase activity, excluding iron [1–3]. In this study, 13 C. neoformans strains isolated from AIDS patients and 7 from bird droppings (B.D.), were examined in order to clarify the effect of different K⁺ concentrations on phenoloxidase activity. A new solid and liquid caffeic acid minimal synthetic medium (MSM-CAF) containing only caffeic acid and ferric citrate with different potassium concentrations was used to evaluate C. neoformans phenoloxidase activity. In the MSM-CAF solid medium the degree of brown pigmentation on the agar plates was read on days 1, 2 and 3 of incubation, and the pigmentation of the C. neoformans strains was classed into 5 categories. The brown pigment of the liquid MSM-CAF test tubes were checked after 24 hours of incubation by measuring the optical density (O.D.) at 480 nm. Three C. neoformans AIDS and B.D. strains, randomlychosen, were tested for phenoloxidase activity, according to the modified protocols of Polachecket al., Torres-Guerrero et al. and Rhodes [2–4]. According to the results obtained, it has been observed that K⁺ does not activate the phenoloxidase activity in the C. neoformans AIDS and B.D. strains. In particular, with an increase in potassium concentrations in the MSM-CAF solid and liquid medium, there was a corresponding inhibition of the phenoloxidase activity on both the C. neoformans AIDS and B.D. strains.This revised version was published online in October 2005 with corrections to the Cover Date.     

Diagnostic performance of multi-organ ultrasound with pocket-sized device in the management of acute dyspnea

Background

The availability of ultra-miniaturized pocket ultrasound devices (PUD) adds diagnostic power to the clinical examination. Information on accuracy of ultrasound with handheld units in immediate differential diagnosis in emergency department (ED) is poor. The aim of this study is to test the usefulness and accuracy of lung ultrasound (LUS) alone or combined with ultrasound of the heart and inferior vena cava (IVC) using a PUD for the differential diagnosis of acute dyspnea (AD).

Methods

We included 68 patients presenting to the ED of “Maurizio Bufalini” Hospital in Cesena (Italy) for AD. All patients underwent integrated ultrasound examination (IUE) of lung-heart-IVC, using PUD. The series was divided into patients with dyspnea of cardiac or non-cardiac origin. We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic methods and their various combinations for the diagnosis of cardiogenic dyspnea (CD), comparing with the final diagnosis made by an independent emergency physician.

Results

LUS alone exhibited a good sensitivity (92.6%) and specificity (80.5%). The highest accuracy (90%) for the diagnosis of CD was obtained with the combination of LUS and one of the other two methods (heart or IVC).

Conclusions

The IUE with PUD is a useful extension of the clinical examination, can be readily available at the bedside or in ambulance, requires few minutes and has a reliable diagnostic discriminant ability in the setting of AD.