Voltammetric stability of anodic films on the Ti6Al4V alloy in chloride medium

The biocompatibility and mechanical integrity of Ti and Ti6Al4V alloy can be affected by corrosion processes. This paper presents studies on the stability of anodic oxide films on Ti6Al4V and Ti in chloride medium. The oxides were grown potentiodynamically up to 8.0 V in the phosphate buffer saline (PBS) solution (pH 6.8) at 25 and 37 °C. The morphology of the obtained anodic oxides and the type of corrosion that occurred were analyzed by SEM–EDS. The Ti6Al4V alloy presented less corrosion resistance than pure Ti. Elemental analyses showed that the decrease of the alloy corrosion resistance is due mainly to the corrosion of Al.     

Laparoscopic adrenalectomy for nonmalignant disease: improved safety, morbidity, and cost-effectiveness

The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission.     

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.     

Boundary layer drug delivery using a helical catheter

BACKGROUND: A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid 'boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. METHODS: The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow system under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate = 100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25-1.0 microg/min) and hirudin (an antithrombin; doses: 10-100 microg/min) were used to inhibit thrombus formation. RESULTS: Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudin) over 1-2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than systemic administration of the same agents. CONCLUSIONS: Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid systemic effects, and can reduce cost of therapy by reducing total drug requirements.     

Common pediatric esophageal disorders

Esophageal disorders in children can result in significant morbidity. The most common esophageal disorder seen in children is gastroesophageal reflux. Other common disorders affecting the esophagus include peptic esophageal strictures, esophageal atresia with or without tracheoesophageal fistula, caustic and foreign body ingestions, achalasia, and cricopharyngeal achalasia. We discuss what is currently known about these common pediatric esophageal disorders with regard to pathophysiology, clinical presentation, and diagnostic and treatment strategies.     

Detection of Epstein-Barr virus in oral scrapes in HIV infection, in hairy leukoplakia, and in healthy non-HIV-infected people

Epstein Barr virus (EBV) has been implicated in the pathogenesis of oral hairy leukoplakia (OHL). EBV is normally detected by lesional biopsy. The objectives of this study were to examine oral scrapes containing squamous epithelial cells (squames) from HIV-infected people with and without clinical lesions of OHL, and from healthy non-HIV-infected controls, for EBV-DNA by the polymerase chain reaction (PCR). EBV-DNA was detected in 65% of HIV-infected people and 20% of healthy HIV-negative controls but in HIV-infected individuals it was found as frequently in those without OHL as in those with. Moreover, EBV-DNA was not detected in all HIV-infected individuals, nor in all OHL. The results suggest that the presence or absence of detectable EBV-DNA in oral scrapes, though a guide, cannot be regarded as absolutely reliable in the diagnosis or exclusion of OHL.     

Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency

Impaired exercise capacity is a common finding in chronic obstructive pulmonary disease (COPD) patients. This reduction is not a simple consequence of airflow limitation. Peripheral muscle weakness, deconditioning and impaired gas exchange, were recognized as important contributors to exercise intolerance. In this overview, the contribution of peripheral muscle function and muscle training to exercise performance is discussed by means of three questions: 1) Is peripheral muscle dysfunction contributing to exercise limitation in COPD? 2) How do we measure peripheral muscle function? 3) Are peripheral muscle training modalities effective? At present, there is substantial evidence for peripheral muscle dysfunction. Both reduced force generating capacity as well as impaired muscle metabolism were observed and these findings contributed substantially to the reduced exercise capacity in COPD. Peripheral muscle strength measurements are feasible with mechanical or electronic devices and revealed muscle weakness in COPD patients. However, this weakness is not uniform for all muscle groups. Upper arm and leg muscles were more affected than hand muscles. This may, at least in part, be related to differences in the levels of inactivity between leg and hand muscles. In addition, muscle weakness is associated with impaired exercise capacity and symptoms of increased exertion during exercise. Endurance exercise training, i.e. cycling and treadmill walking, improved exercise capacity and was associated with alterations in muscle metabolism. Strength training of peripheral muscles showed increases in submaximal exercise performance and quality of life measures. These improvements were observed independently of the degree of airflow obstruction. The optimal training regimen (strength or endurance), and the muscle groups to be trained, remain to be determined.     

TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a paramagnetic surface probe

Surfaces of the 173 residue catalytic domain of human matrix metalloproteinase 3 (MMP-3(DeltaC)) affected by binding of the N-terminal, 126 residue inhibitory domain of human TIMP-1 (N-TIMP-1) have been investigated using an amide-directed, NMR-based approach. The interface was mapped by a novel method that compares amide proton line broadening by paramagnetic Gd-EDTA in the presence and absence of the binding partner. The results are consistent with the X-ray model of the complex of MMP-3(DeltaC) with TIMP-1 (Gomis-Rüth et al. (1997) Nature 389, 77-81). Residues Tyr155, Asn162, Val163, Leu164, His166, Ala167, Ala169, and Phe210 of MMP-3(DeltaC) are protected from broadening by the Gd-EDTA probe by binding to N-TIMP-1. N-TIMP-1-induced exposure of backbone amides of Asp238, Asn240, Gly241, and Ser244 of helix C of MMP-3(DeltaC) to Gd-EDTA confirms that the displacement of the N-terminus of MMP-3(DeltaC) occurs not only in the crystal but also in solution. These results validate comparative paramagnetic surface probing as a means of mapping protein-protein interfaces. Novel N-TIMP-1-dependent changes in hydrogen bonding near the active site of MMP-3(DeltaC) are reported. N-TIMP-1 binding causes the amide of Tyr223 of MMP-3(DeltaC) bound by N-TIMP-1 to exchange with water rapidly, implying a lack of the hydrogen bond observed in the crystal structure. The backbone amide proton of Asn162 becomes protected from rapid exchange upon forming a complex with N-TIMP-1 and could form a hydrogen bond to N-TIMP-1. N-TIMP-1 binding dramatically increases the rate of amide hydrogen exchange of Asp177 of the fifth beta strand of MMP-3(DeltaC), disrupting its otherwise stable hydrogen bond.     

Seed banks and molecular maps: unlocking genetic potential from the wild

Nearly a century has been spent collecting and preserving genetic diversity in plants. Germplasm banks-living seed collections that serve as repositories of genetic variation-have been established as a source of genes for improving agricultural crops. Genetic linkage maps have made it possible to study the chromosomal locations of genes for improving yield and other complex traits important to agriculture. The tools of genome research may finally unleash the genetic potential of our wild and cultivated germplasm resources for the benefit of society.