Methods: Factors influencing labeling outcome (activity, specific

Methods: Factors influencing labeling outcome (activity, specific activity, time, final volume, stability) were studied separately. The critical steps of a standard radiolabeling procedure were optimized to reduce finger exposure, developing an alternative labeling procedure and including a different Y-90 supplier. Finger doses were monitored by thermoluminescent dosimeters at each fingertip under anti-X

gloves, considering both absolute values and values after normalization to 1.48 GBq.

Results: Labeling of Y-90-Zevalin was safe and reproducible up to 7.4 GBq with a simple and single-step procedure offering good stability for several hours. Radiolabeling specific activity was found critical, being kept at 740 MBq.mg(-1). click here Radiochemical purity values >= 98% were routinely achieved. The alternative procedure allowed a sensible ��-Nicotinamide concentration reduction of finger dose, due to both the different Y-90 vial and the handling. Finger exposure was reduced from 6.6 +/- 4.3 to 3.1 +/- 0.8 mSv/1.48 GBq in the case of the original Y-90 vial and from 1.5 +/- 0.9 to 0.3 +/- 0.1 mSv/ 1.48 GBq using a shielded Y-90 vial.

Conclusions: HD-Zevalin can be prepared in a safe and reproducible way, giving high

radiochemical purity values, good stability and low finger exposure. This study may improve the safety of nuclear medicine professionals involved in the preparation of Zevalin. (C) 2010 Elsevier Inc. All rights reserved.”
“The ability of herpes simplex virus to persist in

cells depends on the extent of viral-gene expression, which may be controlled by epigenetic mechanisms. We used quiescent infection with the viral mutants d109 and d106 to explore the effects of cell type and the presence of the viral protein ICP0 on the expression and chromatin structure of the human cytomegalovirus (HCMV) tk and gC promoters on the viral genome. Expression from the HCMV promoter on the d109 genome decreased with time and was considerably buy PS-341 less in HEL cells than in Vero cells. Expression from the HCMV promoter in d106 was considerably more abundant than in d109, and this increased with time in both cell types. The same pattern of expression was seen on the tk and gC genes on the viral genomes, although the levels of tk and gC RNA were approximately 10(2)- and 10(5)-fold lower than those of wild-type virus in d106 and d109, respectively. In micrococcal-nuclease digestion experiments, nucleosomes were evident on the d109 genome, and the amount of total H3 as determined by chromatin immunoprecipitation was considerably greater on d109 than d106 genomes. The acetylation of histone H3 on the d106 genomes was evident at early and late times postinfection in Vero cells, but only at late times in HEL cells. The same pattern was observed for H3 acetylated on lysine 9.

Paeoniflorin is the main active glycoside of peony The purpose o

Paeoniflorin is the main active glycoside of peony. The purpose of this study

was to evaluate the antidepressant-like effects of paeoniflorin in a rat model of chronic unpredictable stress (CUS) and its active mechanisms. The results showed that CUS-exposed rats exhibited depressive-like behaviour with reduced weight, low motor activity as well as reduced consumption of sucrose, biochemical changes CFTRinh-172 molecular weight with increased concentrations of corticosterone and adrenocorticotropic hormone and neurochemical changes with reduced monoamine neurotransmitter levels. Paeoniflorin treatment markedly increased sucrose consumption and decreased serum corticosterone and adrenocorticotropic hormone levels in the CUS-treated rats. Furthermore, paeoniflorin treatment significantly attenuated CUS-induced reductions in noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid as well as CUS-induced increases in the ratio between the latter two factors. These results suggest that the modulation of the hypothalamic-pituitary-adrenal Poziotinib nmr axis and up-regulation of serotonergic and noradrenergic systems are important mechanisms underlying the antidepressant-like effects of paeoniflorin in CUS-treated rats. (C) 2013 Elsevier Ireland Ltd. All rights

reserved.”
“Objective: Our objective was to summarize our experience with tracheobronchial reconstructions using bronchoplastic closure for airway defects after noncircumferential resections of bronchogenic carcinoma involving the carina or tracheobronchial angle.

Methods: From January 1990 to December 2005, all patients who underwent tracheobronchial reconstructions with bronchoplastic closure for bronchogenic carcinoma involving the carina or tracheobronchial angle were included. The clinical data for patients were collected retrospectively, including demographic characteristics, occurrences of postoperative complications, and survival.

Results: A total of 40 patients were eligible,

IPI145 cell line including 23 who had right pneumonectomies, 6 who had right upper lobectomies, and 11 who had left pneumonectomies, associated with lower lateral wall of the trachea resections or with partial carinal resections for centrally localized tumors. The airway defects ranged from 0.5 X 2 cm to 2 3 4 cm and involved up to 50% of the airway circumference. Microscopic residual disease was found postoperatively at the bronchial margin in 20% (8/40). Of 40 patients, 2 (5.0%) had pulmonary atelectasis develop, 2 (5.0%) arrhythmia, 2 (5.0%) bronchopleural fistula, and 1 (2.5%) airway stenosis after operation. Thirty-day mortality was 2.5%(1/40). Median survival for 40 patients was 18.5 months with a cumulative survival of 72.2%, 26.6%, and 21.3% at 1, 3, and 5 years, respectively.

Following removal of the outer lipid/protein membrane, a layer 20

Following removal of the outer lipid/protein membrane, a layer 20 to 40 nm in thickness was encountered

that was composed of fibrous elements which, under reducing conditions, rapidly decomposed into individual monomers on the substrate. Beneath this layer was the virus core and its prominent lateral bodies, which could be dissociated or degraded with proteases. The core, in addition to the lateral bodies, PD0325901 manufacturer was composed of a thick, multillayered shell of proteins of diverse sizes and shapes. The shell, which was readily etched with proteases, was thoroughly permeated with pores, or channels. Prolonged exposure to proteases and reductants produced disgorgement of the viral DNA from the remainders of the cores and also left residual, flattened, protease-resistant sacs on the imaging substrate. Selleckchem Entrectinib The DNA was readily visualized by AFM, which revealed some

regions to be “”soldered”" by proteins, others to be heavily complexed with protein, and yet other parts to apparently exist as bundled, naked DNA. Prolonged exposure to proteases deproteinized the DNA, leaving masses of extended, free DNA. Estimates of the interior core volume suggest moderate but not extreme compaction of the genome.”
“Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the frontal and occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA,

Choline, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind manner with either haloperidol or quetiapine. Blasticidin S solubility dmso (1)H-MRS was repeated every 6 months for up to 2 years. There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls. Global NAA was directly related to measures of global cognitive performance in the whole subject sample. Following treatment with haloperidol or quetiapine, there were no changes in NAA in any of the regions studied. Early in the illness, schizophrenia patients already demonstrate subtle reductions in NAA. Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes.”
“CD8 T cells play a major role in antiviral immune responses. Their importance for progression to chronic hepatitis C and response to treatment are still unclear.

(C) 2010 Elsevier Ireland Ltd All rights reserved “
“Optima

(C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Optimal functional recovery after stroke is the most important to improve quality of life. Contralateral hemisphere of infarction site plays an important role for the recovery. The underlying processes in contralateral hemisphere during recovery have not see more yet been

fully elucidated. We have previously reported the increase in synaptic turnover in the contralateral somatosensmy cortex (SSC) during 1st week after infarction of the unilateral SSC. The neuronal circuit was remodeled after this period to process bilateral information in the remaining hemisphere, and functional compensation was achieved. In the present study, we used in vivo electrophysiological recording to detect the current source density (CSD) for somatosensory input. Interestingly, a specific CSD pattern was detected in the layer II/III region of contralateral SSC

and the duration was significantly correlated with functional recovery. These results VEGFR inhibitor indicate that the compensational remodeling of neuronal circuit in the intact hemisphere may be dominantly induced in layer II/III neurons. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Aims: This study was designed to characterize a beta-glucosidase of Oenococcus oeni ST81, a strain isolated from a Spanish wine of the origin appellation Ribeira Sacra. Methods and

Results: The beta-glucosidase of O.similar to oeni ST81 seems to have a periplasmic localization into the cells. This activity was strongly inhibited by gluconic acid, partially inhibited by glucose and not inhibited by fructose, lactate, malate, mannitol or sorbitol. Ethanol increased the activity of this enzyme up to 147%. Among the several metal ions assayed, only Fe2+ (10 mmol l-1) and Cu2+ (5 mmol l-1) exhibited a partial inhibitory effect (40%). This enzyme was partially purified using a combination of ammonium sulfate precipitation and chromatographic methods. The single peak because of beta-glucosidase in all chromatographic columns indicates the presence selleck chemicals llc of a single enzyme with an estimated molecular mass of 140 kDa. The calculated Km and Vmax values for 4-nitrophenyl-beta-d-glucopyranoside were 0.38 mmol l-1 and 5.21 nmol min-1, respectively. The enzyme was stable at pH 5.0 with a value of t1/2 = 50 days for the crude extract. Conclusions: The beta-glucosidase of O.similar to oeni ST81 is substantially different from those characterized from other wine-related lactic acid bacteria (LAB), such as Lactobacillus plantarum and Lactobacillus brevis; however, it appears to be closely related to a beta-glucosidase from O.similar to oeni ATCC BAA-1163 cloned into Escherichia coli.

When the cue directed attention to low contrast signal dots prese

When the cue directed attention to low contrast signal dots presented in high contrast noise, coherent motion thresholds were only enhanced for the group with dyslexia. This manipulation produced equivalent coherent motion thresholds in the reader groups. In other conditions, the group with dyslexia had significantly higher coherent motion thresholds than the control group. It was concluded that adults with dyslexia who show evidence of a coherent motion deficit (37% of the dyslexia group in each experiment), have a specific difficulty in noise

exclusion. This appears to occur as consequence of a sensory processing deficit in the magnocellular or dorsal stream. (C) 2012 Elsevier Ltd. All rights reserved.”
“Objective: Blood pressure gradients that are noted early after repair of coarctation in neonates and infants are often attributed to proximal arch hypoplasia. Rapid growth of Etomoxir mouse the hypoplastic proximal arch is usually observed, although in some individuals

an early gradient predicts the subsequent need for reintervention. To define the predictive reliability of blood pressure gradients between arms and legs and to identify predictors of arch growth, we undertook a retrospective study.

Methods: Between January 2000 and June 2008, 77 infants underwent surgical repair of coarctation. Data collected included preoperative dimensions of aortic segments. Blood pressure gradients between arms and legs determined by cuff were compared

intraoperatively and postoperatively, as well as 2-dimensional AICAR research buy echocardiographic dimensions of the aorta between those who did not require reintervention for recoarctation (group A) and those who did (group B). Receiver operating characteristic curve analysis was applied to BGJ398 nmr evaluate discrimination of the systolic gradient in differentiating the 2 groups of patients.

Results: At surgery, patients’ median age was 10 days and weight was 3.3 kg. There was 1 early death. Median follow-up was 40 months (interquartile range, 24-63 months). Recoarctation developed in 11 patients (14.3%), defined as a resting blood pressure gradient of greater than 20 mm Hg with a corresponding decrease in the diameter of the aorta by 50%. Freedom from recoarctation was 87% at 1 year and 85% at 5 years. Multivariable logistic regression analysis identified the size of the ascending aorta as a risk factor for recoarctation. Blood pressure gradient at the end of surgery was not predictive of recoarctation. The ascending aorta and transverse arch showed rapid growth in group A, and this was associated with a decrease in blood pressure gradient over time. In comparison, the growth of the ascending aorta and arch in group B was significantly less than in group A and associated with worsening of gradients.

Results: Tc-99m-HABBN was synthesized with high radiochemical yie

Results: Tc-99m-HABBN was synthesized with high radiochemical yield, purity and specific activity. There were no significant changes in clinical parameters, and there were no adverse or subjective side effects. Low metabolic stability was observed, as less than 20% of Tc-99m-HABBN was intact after 30 min. Immunohistochemical staining for GRPR was observed in the prostate cancer specimens in all patients. Tc-99m-HABBN scintigraphy and SPECT/CT did not detect prostate cancer in patients with proven disease.

Conclusions: Tc-99m-HABBN SPECT/CT for visualization of prostate cancer is safe but hampered by an unexpected low in vivo metabolic stability

in man. The difference between the excellent in vitro stability of Tc-99m-HABBN in human serum samples determined https://www.selleckchem.com/products/cl-amidine.html in our previous study regarding Tc-99m-HABBN and the low in vivo metabolic stability determined in this study, is striking. This issue warrants further study of peptide-based radiopharmaceuticals. (C) 2013 Elsevier Inc. All rights reserved.”
“Allograft rejection remains a major limitation to successful solid organ transplantation. Here,

we investigated the biosynthesis and bioactions of the pro-resolving mediators lipoxin A(4) and resolvin E1 in host responses to organ transplantation. In samples obtained during screening bronchoscopy after human lung transplantation, bronchoalveolar lavage fluid levels of lipoxin A(4) were Silmitasertib price increased in association with the severity of allograft rejection that was graded independently by clinical pathology. Lipoxin A(4) significantly BV-6 clinical trial inhibited calcineurin activation in human neutrophils, and lipoxin A(4) stable analogs prevented acute rejection of vascularized cardiac and renal allografts. Transgenic animals expressing human lipoxin A(4) receptors revealed important sites of action in host tissues for lipoxin A(4)’s protective effects. Resolvin E1 displays counter-regulatory actions for leukocytes, in part, via increased lipoxin A(4) biosynthesis, yet RvE1 administered (1 mu g, iv) to donor (days – 1 and 0) and recipient mice (days – 1, 0 and +4) was even more potent than a lipoxin stable analog

(1 mu g, iv) in prolonging renal allograft survival (median survival time=74.0 days with RvE1 and 37.5 days with a LXA(4) analog). Together, these results highlight the potential for pro-resolving mediators in prolonging survival of solid organ transplants. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objective: The present study aimed to assess the usefulness of routine monitoring of cardiac troponin I concentrations within 24 hours of surgery (cTn-I<24h) in neonates and infants undergoing cardiac surgery.

Methods: The added predictive ability of a high peak cTn-I<24h (within the upper quintile per procedure) for a composite outcome, including 30-day mortality and severe morbidity, was assessed retrospectively.


“Objective: Radial artery harvesting has been questioned b


“Objective: Radial artery harvesting has been questioned because of purported long-term circulatory consequences. Previous midterm Doppler ultrasonographic results are inconsistent regarding ulnar arterial effects. Flow-mediated vasodilatation more sensitively measures response to shear stress as index of arterial reactivity and function.

Methods: We contacted 231 patients who had undergone radial artery harvesting at least 10 years previously (mean follow-up, 12.9 +/- 0.8 years). Subcohort of 25 volunteers (mean age, 69.2 +/- 8.4 years) underwent ultrasonographic evaluation of ipsilateral (harvest) and contralateral (control) ulnar arteries. Flow-mediated

vasodilatation compared changes in ulnar arterial diameters before and after occlusion.

Results: In subcohort, peak systolic velocity of harvest ulnar artery was 0.82 +/- 0.15 m/s, versus 0.63 +/- 0.23 m/s this website on control side (P < .001), with no differences in intimomedial thickness (P = .763) or presence of atherosclerotic plaques (P = .364). Baseline diameter of harvest ulnar artery was 3.0 +/- 0.5 mm, versus 2.7

+/- 0.6 mm on control side (P = .007). Postocclusion diameter of harvest ulnar artery was 3.2 +/- 0.5 mm, versus 2.9 +/- 0.6 mm on control side (P = .001). No differences were seen check details in preocclusion and postocclusion absolute and percentage changes in ulnar arterial diameter (Table 1).

Conclusions: Despite increased shear stress, no deterioration in either ulnar arterial structure or functional reactivity was measured by flow-mediated vasodilatation more than 10 years after radial artery harvesting. With appropriate preoperative evaluation, radial arterial grafting for coronary artery bypass grafting is not associated with long-term donor limb vascular

insufficiency. (J Thorac Cardiovasc Surg 2011;142:298-301)”
“Gonadotropin-releasing hormone (GnRH) is the central regulator of gonadotropins, which stimulate gonadal function. Hypothalamic neurons that produce kisspeptin and neurokinin B stimulate GnRH release. Inactivating mutations in the genes Lapatinib encoding the human kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin B (TAC3), and the neurokinin B receptor (TACR3) result in pubertal failure. However, human kisspeptin loss-of-function mutations have not been described, and contradictory findings have been reported in Kiss1-knockout mice. We describe an inactivating mutation in KISS1 in a large consanguineous family that results in failure of pubertal progression, indicating that functional kisspeptin is important for puberty and reproduction in humans. (Funded by the Scientific and Technological Research Council of Turkey [TUBITAK] and others.)”
“Repetition is a central phenomenon of behavior, and researchers have made extensive use of it to illuminate psychological functioning.

WT mice treated

WT mice treated GSK J4 molecular weight with both ISO and T09 had decreased renal renin, ACE and AT(1)R mRNA expression compared with mice treated with ISO only. Cardiac ACE mRNA expression was also reduced in the hearts of WT mice treated with ISO and T09 compared

with those treated with ISO alone. The transcriptional changes of renin, ACE and AT(1)R were mostly absent in mice deficient for LXR-alpha, suggesting that these effects are importantly conferred through LXR-alpha. In conclusion, LXR-alpha activation blunts ISO-induced increases in mRNA expression of renin, AT(1)R and ACE in the heart and kidney. These findings suggest a role for LXR-alpha in RAAS regulation. Laboratory Investigation (2010) 90, 630-636; doi: 10.1038/labinvest.2010.7; published online 1 February 2010″
“Adipose

tissue is one of the promising sources of multipotent stem cells in human. Human multipotent adipose-derived stem (hMADS) cells have recently been isolated and showed differentiation potential into multiple mesenchymal lineages in vitro and in vivo. On the basis of these evidences, we examined the therapeutic efficacy of hMADS cells for fracture healing in an immunodeficient rat femur non-union fracture model. Local transplantation of hMADS cells radiographically and histologically promoted fracture healing with significant improvement of biomechanical function at the fracture sites compared with local transplantation of human fibroblasts (hFB) or PBS administration. Histological capillary density and physiological blood flow by laser Doppler selleck inhibitor perfusion imaging were significantly greater in hMADS group than hFB and PBS groups. Expressions of intrinsic (rat) bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and angiopoietin-1 in peri-fracture tissue were upregulated in hMADS group than other groups. In addition, presence of BMP-2

or Selleckchem Erastin VEGF activated the proliferation and migration of hMADS cells in vitro. These results indicate that hMADS cells stimulate the interaction between the transplanted cells and the resident cells stronger than other cells, and they promote fracture healing more effectively. Furthermore, immunohistochemistry for human-specific antibodies revealed direct differentiation of hMADS cells into osteoblasts or endothelial cells in newly formed callus or vasculature, respectively. RT-PCR for human-specific primers for osteogenic/endothelial markers also disclosed osteogenic and vasculogenic plasticity of the transplanted hMADS cells at the early stage of fracture healing. The present results suggest that transplantation of hMADS cells may become a useful strategy for cell-based bone regeneration in the future clinical setting. Laboratory Investigation (2010) 90, 637-649; doi: 10.1038/labinvest.2010.39; published online 15 February 2010″
“The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning.

The attenuated DA response in alpha CaMKIIT286A mice was in line

The attenuated DA response in alpha CaMKIIT286A mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human Belnacasan mouse condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest alpha CaMKII autophosphorylation as a

facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.”
“Background: Oxytocin (OXT) and prolactin (PRL) are neuropeptide hormones that interact with the serotonin system and are selleck screening library involved in the stress response and social affiliation. In human studies, serum OXT and PRL levels have been associated with depression and related phenotypes. Our purpose was to determine if single nucleotide polymorphisms (SNPs) at the loci for OXT, PRL and their receptors, OXTR and PRLR, were associated with childhood-onset mood disorders (COMD).

Methods: Using 678 families

in a family-based association design, we genotyped 16 SNPs at OXT, PRL, OXTR and PRLR to test for association with COMD.

Results: No significant associations were found for SNPs in the OXTR, PRL, or PRLR genes. Two of

three SNPs 3′ of the OXT gene were associated with COMD (p <= 0.02), significant after spectral decomposition, but were not significant after additionally correcting for the number of genes tested. Supplementary analyses of Tozasertib molecular weight parent-of-origin and proband sex effects for OXT SNPs by Fisher’s Exact test were not significant after Bonferroni correction.

Conclusions: We have examined 16 OXT and PRL system gene variants, with no evidence of statistically significant association after correction for multiple tests. (C) 2010 Elsevier Ltd. All rights reserved.”
“According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate+glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge.

Limitations include the lack of detailed characterization and lim

Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated

data gaps and research needs are also enumerated in this review.”
“There is immunohistochemical evidence for endothelin ( ET) receptors in satellite glial cells in sensory ganglia, but there is no information on the function of these receptors. We used calcium imaging to study this question in isolated mouse trigeminal ganglia and found that satellite glial cells are highly sensitive to ET-1, with threshold at 0.05 nM. Responses displayed strong desensitization at ET-1 concentrations of more than 1 nM. A large component of the response persisted when Ca(2+) was deleted from the external medium, consistent with Ca(2+) release from internal stores. The use of receptor Silmitasertib in vivo selective agents showed that the responses were mediated by ETB receptors. We conclude that satellite glial cells display H 89 research buy endothelin receptors, which may participate in neuron-glia communications in the trigeminal ganglia. NeuroReport 22:465-469 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Much

of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency

of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms Everolimus nmr associated with asbestos particle toxicity involve two facets for each particle’s contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems.