Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/beta-thalassemia patient

Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/beta-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombin-antithrombin III complex (TAT) levels and right-sided cardiac catheterization were used to monitor changes after treatment. Reduction of plasma TAT levels from 7.5 to 3.8 microg/L (normal, 3 +/- 2.4 microg/L), pulmonary vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm(-5) (normal, 67 +/- 30 dyne.sec.cm(-5)), and mean pulmonary arterial pressure from 51 to 32 mm Hg (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood hypercoagulability as reflected in plasma TAT level by chronic blood transfusion was the likely basis for improvement of increased PVR, being secondary to thrombotic pulmonary arteriopathy and subsequently PHT.     

Focal Modulation of the Primary Motor Cortex in Fibromyalgia Using 4×1-Ring High-Definition Transcranial Direct Current Stimulation (HD-tDCS): Immediate and Delayed Analgesic Effects of Cathodal and Anodal Stimulation

Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4×1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population.Perspective4×1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored.     

Sclerosing therapy for orbital lymphangioma using sodium tetradecyl sulfate

PURPOSE: To describe the results of intralesional injection of the sclerosing agent sodium tetradecyl sulfate in patients with orbital lymphangioma. METHODS: Four young patients with a history of orbital lymphangioma were treated on one or more occasions with percutaneous puncture and injection of sodium tetradecyl sulfate under computed tomography guidance. Resolution of the signs and symptoms, complications resulting from surgery, and recurrence of bleeding were studied. RESULTS: Three patients with a long-standing history of unilateral proptosis and one patient with progressive unilateral visual loss from multiple recurrent orbital hemorrhages were studied. Treatment ranged from one to three sodium tetradecyl sulfate injections. All patients showed improvement of their signs and symptoms after treatment. A decrease in the size of lesions was demonstrated by orbital imaging. Visual acuity and intraocular pressure remained unchanged. Complications included transient postoperative localized inflammation in all cases and transient ophthalmoparesis in one patient. Follow-up time ranged between 15 and 36 months, during which no recurrence of bleeding was observed. CONCLUSIONS: Our study suggests that intralesional injection of sodium tetradecyl sulfate under computed tomography guidance is an effective treatment for patients with orbital lymphangioma and is not associated with vision-threatening complications.     

Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol

OBJECTIVE: Administration of the beta-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both beta1-adrenergic and beta2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. METHODS: We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype beta1-adrenergic and beta2-adrenergic receptor polymorphisms. RESULTS: When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other beta1-adrenergic and beta2-adrenergic receptor polymorphisms (P>0.05). CONCLUSION: In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.     

Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure

Understanding molecular-scale architecture of cells requires determination of 3D locations of specific proteins with accuracy matching their nanometer-length scale. Existing electron and light microscopy techniques are limited either in molecular specificity or resolution. Here, we introduce interferometric photoactivated localization microscopy (iPALM), the combination of photoactivated localization microscopy with single-photon, simultaneous multiphase interferometry that provides sub-20-nm 3D protein localization with optimal molecular specificity. We demonstrate measurement of the 25-nm microtubule diameter, resolve the dorsal and ventral plasma membranes, and visualize the arrangement of integrin receptors within endoplasmic reticulum and adhesion complexes, 3D protein organization previously resolved only by electron microscopy. iPALM thus closes the gap between electron tomography and light microscopy, enabling both molecular specification and resolution of cellular nanoarchitecture.     

Toughened chitosan-based composite membranes with antibiofouling and antibacterial properties via incorporation of benzalkonium chloride

Biofouling due to biofilm formation is a major problem in ultrafiltration membrane applications. In this work, a potential approach to solve this issue has been developed by functionalization of chitosan-based membranes with benzalkonium chloride (BKC). The chitosan composite membranes consisting of poly(ethylene glycol) (PEG), multiwalled carbon nanotubes (MWCNT), and BKC were synthesized by mixing the membrane precursors and the antibacterial solution, and casting via an inversed phase technique. The effects of the BKC content on the morphology and performance of the membranes are investigated by varying the BKC feed compositions. The composite membranes demonstrate better antibacterial efficacy against Staphylococcus aureus than Escherichia coli. The permeability and selectivity performances of the composites as filter membranes are examined by employing a dead-end filtration system. Interestingly, enhanced toughness of the membranes is observed as a function of the BKC content. Mechanisms of the structural formation are investigated. The results from SEM, XRD, and FTIR spectroscopy revealed that MWCNT/BKC are located as nanoclusters with π–π stacking interactions, and are covered by PEG chains. The shape of the dispersed domains is spherical at low BKC contents, but becomes elongated at high BKC contents. These act as soft domains with an anisotropic shape with toughening of the brittle chitosan matrix, leading to enhanced durability of the membranes, especially in ultrafiltration applications. The composite membranes also demonstrate improved rejection in dead-end ultrafiltration systems due to high porosity, high hydrophilicity, and the positive charges of the membrane surface.

Chitosan/PEG/MWCNT/BKC membranes exhibit enhanced antibiofouling properties against S. aureus and E. coli. MWCNT/BKC are located as dispersed nano-clusters with π–π stacking interactions in the chitosan matrix, and are coved by PEG chains.     

Electrophilic halogenations of propargyl alcohols: paths to α-haloenones, β-haloenones and mixed β,β-dihaloenones

The Meyer–Schuster rearrangement of propargyl alcohols or alkynols leading to α,β-unsaturated carbonyl compounds is well known. Yet, electrophilic halogenations of the same alkynols and their alkoxy, ester and halo derivatives are inconspicuous. This review on the halogenation reactions of propargyl alcohols and derivatives intends to give a perspective from its humble direct halogenation beginning to the present involving metal catalysis. The halogenation products of propargyl alcohols include α-fluoroenones, α-chloroenones, α-bromoenones and α-iodoenones, as well as β-haloenones and symmetrical and mixed β,β-dihaloenones. They are, in essence, tri and tetrasubstituted alkenes carrying halo-functionalization at the α- or β-carbon. This is a potential stepping stone for further construction towards challenging substituted alkenones via Pd-catalysed coupling reactions.

This review highlights the development of α-haloenone, β-haloenone and mixed β,β-dihaloenone formations from propargyl alcohols via direct electrophilic halogenations and metal catalysed-halonium interception rearrangements.