Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral to calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. Time-lapse light-sheet imaging of mouse embryos revealed calvarial progenitors intercalate in 3D in the CM above the eye, and exhibit protrusive and crawling activity more apically. CM cells express non-canonical Wnt/planar cell polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand Wnt5a-/- mutants have less dynamic cell rearrangements and protrusive activity. Loss of CM-restricted Wntless (CM-Wls), a gene required for secretion of all Wnt ligands, led to diminished apical expansion of Osx+ calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.

Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues.

The skull roof, or calvaria, is comprised of interlocking plates of bones that encase the brain. Separating these bones are fibrous sutures that permit growth. Currently, we do not understand the instructions for directional growth of the calvaria, a process which is error-prone and can lead to skeletal deficiencies or premature suture fusion (craniosynostosis, CS). Here, we identify graded expression of fibronectin (FN1) in the mouse embryonic cranial mesenchyme (CM) that precedes the apical expansion of calvaria. Conditional deletion of Fn1 or Wasl leads to diminished frontal bone expansion by altering cell shape and focal actin enrichment, respectively, suggesting defective migration of calvarial progenitors. Interestingly, Fn1 mutants have premature fusion of coronal sutures. Consistently, syndromic forms of CS in humans exhibit dysregulated FN1 expression, and we also find FN1 expression altered in a mouse CS model of Apert syndrome. These data support a model of FN1 as a directional substrate for calvarial osteoblast migration that may be a common mechanism underlying many cranial disorders of disparate genetic etiologies.

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve-induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.

Nose to brain delivery of naringin loaded transniosomes for epilepsy: formulation, characterisation, blood-brain distribution and invivo pharmacodynamic evaluation.

The current work limns the preparation of naringin-loaded transnioosomes (NRN-TN) to enhance NRN solubility, permeation and bioavailability via nasal mucosa for intranasal delivery. NRN-TN was created by the thin-film hydration technique, and with the BBD (Box-Behnken design), optimisation was carried out. NRN-TNopt was characterised for the vesicle size, PDI (Polydispersity index), zeta potential, entrapment efficiency (EE) and in vitro NRN release. For further assessment, nasal permeation study, study of Blood-brain distribution, TEM (Transmission Electron Microscopy), and CLSM (Confocal Scanning Laser Microscopy) were conducted withal. The NRN-TNopt exhibited spherical as well as sealed vesicles with a considerable small size of 151.3 nm, an EE of 75.23 percent, a PDI of 0.1257, and an in vitro release of 83.32 percent. CLSM investigation revealed that the new formulation allows for higher NRN permeation across nasal mucosa than the NRN solution. The blood-brain distribution investigation revealed that intranasally administered NRN-TN had a greater Cmax and AUC0-24 h than orally administered NRN-TN. Seizure activity and neuromuscular coordination as measured by the rotarod test, biochemical estimate of oxidative stress indicators, and histological investigations demonstrated that the NRN-TN has superior anti-epileptic potential in comparison to the standard diazepam. In addition, nasal toxicity studies demonstrate that the NRN-TN formulation is safer for intranasal administration. This study confirmed that the created TN vesicle formulation is a valuable carrier for the intranasal administration of NRN for the treatment of epilepsy.

Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs.

NEW FINDINGS: What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition. ABSTRACT: The carotid body chemoreceptors (CBC) play an important role in the adaptive counter-regulatory response to hypoglycaemia by evoking the CBC-mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin-induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin-induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin-induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5-100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation ( V ̇ $\dot V$ E ) with significant (P < 0.0001) effects on heart rate and blood pressure. Insulin-mediated effects on CSN and cardiorespiration were sustained and the change in V ̇ $\dot V$ E was driven by tidal volume only. Insulin significantly (P < 0.0001) lowered blood glucose level. NaCN-mediated CSN activity and V ̇ $\dot V$ E were significantly (P < 0.0001) augmented during insulin-induced hypoglycaemia. The augmented V ̇ $\dot V$ E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P < 0.0001) exacerbated during insulin-induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin-induced hypoglycaemia on CBC chemosensitivity to potentiate CBC-mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter-regulatory responses to restore normoglycaemia.

Monascin and ankaflavin-Biosynthesis from Monascus purpureus, production methods, pharmacological properties: A review.

Monascus purpureus copiously yields beneficial secondary metabolites , including Monascus pigments, which are broadly used as food additives, as a nitrite substitute in meat products, and as a colorant in the food industry. Monascus yellow pigments (monascin and ankaflavin) have shown potential antidiabetic, antibacterial, anti-inflammatory, antidepressant, antibiotic, anticancer, and antiobesity activities. Cosmetic and textile industries are other areas where it has established its potential as a dye. This paper reviews the production methods of Monascus yellow pigments, biosynthesis of Monascus pigments from M. purpureus, factors affecting yellow pigment production during fermentation, and the pharmacological properties of monascin and ankaflavin.

Application of QbD based approach in development and validation of RP-HPLC method for simultaneous estimation of methotrexate and baicalin in dual-drug-loaded liposomes.

The present study delineates the development of a novel, rugged and sensitive stability-indicating risk-based HPLC method for the concurrent estimation of methotrexate (MTX) and baicalin (BCL) in dual-drug-loaded-nanopharmaceuticals based on an analytical quality-by-design approach. Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage of orthophosphoric acid and percentage of acetonitrile, that influence the critical quality attributes. Box-Behnken design was utilized for the optimization of the tailing factor as the response for MTX and BCL in a short run time. The chromatographic conditions were optimized by performing 17 experimental runs using design expert software. The chromatographic conditions were selected after the analysis of the optimized zone within the confines of the design space: water:acetonitrile adjusted to a pH of 3.0 with 0.05% orthophosphoric acid (60:40, %v/v) was the mobile phase, the flow rate was 1.0 ml/min and an analytical C18 column was used at an isobestic wavelength of 282 nm. Furthermore, the optimized method was validated in accordance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and was found to be within the prescribed limits. Therefore, the developed reversed-phase-high-performance liquid chromatography method has a high degree of practical utility for synchronous detection of MTX and BCL in pharmaceutical nano-dosage forms such as protein-based nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in in vivo and in vitro studies.

Quality by design-based development and validation of an HPLC method for simultaneous estimation of pregabalin and piperine in dual drug-loaded liposomes.

The current research work describes the development of a rapid HPLC method for the concurrent detection of pregabalin and piperine in dual drug-loaded nanoformulations. The primary goal was to recognize the chromatographic conditions wherein propitious segregation of the integrants with quality peaks can be attained. An attempt to expound the target analytical profile was made to accomplish this goal, and critical method attributes (CMAs), viz. percentage acetonitrile content, injection volume and pH, which affect critical quality attributes (CQAs), were identified using systemic risk analysis. Box-Behnken design was employed to develop a relationship between CMAs and CQAs, which engenders an analytical design space. Efficient chromatographic separation for pregabalin and piperine was attained using an analytical C18 column and mobile phase comprising acetonitrile-water (pH 6.9; 70:30%, v/v) in an isocratic elution mode with a 1 ml/min flow rate. The elution was descried at an isosbestic wavelength of 221 nm using a photodiode array detector. The International Conference on Harmonization guidelines were adopted for the developed HPLC method. The validated HPLC method can be further utilized for the simultaneous quantification and detection of pregabalin and piperine in other lipid-based nanopharmaceuticals such as polymeric nanoparticles, nanocrystals, solid-lipid nanoparticles, metallic nanoparticles, etc., in in vitro and in vivo studies.

Application of a Quality by Design-based approach in development and validation of an RP-HPLC method for simultaneous estimation of methotrexate and mangiferin in dual drug-loaded liposomes.

The present study delineates the development of a novel rugged and sensitive stability-indicating risk-based HPLC method for the concurrent estimation of methotrexate and mangiferin in dual drug-loaded nanopharmaceuticals based on an analytical QbD approach. Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage orthophosphoric acid content and percentage methanol content, that influence critical quality attributes. Box-Behnken design was utilized for the optimization of the tailing factor as response for methotrexate and mangiferin in short run time. The chromatographic conditions were optimized by performing 17 experimental runs acquired from Design-Expert software. The chromatographic conditions after the analysis of an optimized zone within the confines of the design space were chosen as mobile phase water-methanol adjusted to pH 3.0 with 0.05% orthophosphoric acid (65:35, v/v) and flow rate 1.0 ml/min using a C18 analytical column at an isosbestic wavelength of 265 nm. Furthermore, the validation of the optimized method was done in accordance with International Conference on Harmonization guidelines and were reckoned to be in the prescribed limits. The developed RP-HPLC method has a high degree of practical utility for synchronous detection of methotrexate and mangiferin in pharmaceutical nano-dosage forms such as protein-based-nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in in vivo and in vitro studies.

Application of QbD-based approach to the development and validation of an RP-HPLC method for simultaneous estimation of pregabalin and naringin in dual-drug loaded liposomes.

The current work delineates the development of a novel, rugged and sensitive stability-indicating risk-based HPLC method based on an analytical quality-by-design (QbD) approach for the concurrent estimation of naringin and pregabalin in dual-drug-loaded nanopharmaceuticals. Preliminary screening trials were conducted, along with systemic risk analysis, in order to identify the critical method attributes, namely injection volume, pH and acetonitrile content, that influence critical quality attributes. The Box-Behnken design was used to optimize the tailing factor as a response to pregabalin and naringin in a short run time. The chromatographic conditions were improved by running 17 experimental runs generated by design expert software. After analysing the optimized zone within the confines of the design space, the following chromatographic conditions were chosen: mobile phase water-acetonitrile adjusted to pH 6.9 with phosphate buffer (80:20, %v/v), at flow rate of 1.0 ml/min using a C18 analytical column at an isobestic wavelength of 212 nm. Furthermore, the optimized method was validated in accordance with International Conference on Harmonization guidelines and was found to be within the prescribed limits. The developed RP-HPLC method has a high degree of practical utility in in vivo and in vitro studies for the synchronous detection of pregabalin and naringin in pharmaceutical nanodosage forms such as protein-based nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles.

Structural, morphological, and optical characteristics of Gd2 Si2 O7 :Dy3+ nanophosphors for WLEDs.

Yellowish-white light-emitting Gd2-x Si2 O7 :xDy3+ (x = 1-5 mol%) nanophosphors were prepared using a solution combustion synthesis method. Fluorescence spectrophotometry and X-ray diffraction measurements were performed to scrutinize the optical performances and phase recognition of the designated nanophosphors. The outcomes specified that the prepared phosphors were crystallized into a triclinic phase with a P-1 space group. As the concentration of Dy3+ ions was increased, the unit-cell volume decrease proportionally due to the replacement of large-sized Gd3+ by small-sized Dy3+ ions. Under ultraviolet excitation at 349 nm, emission spectra consisted of two pronounced emission lines at ~482 nm (blue line), ~578 nm (yellow line), and a relatively weaker emission at ~670 nm (red line) due to 4 F9/2 →6 H15/2 , 4 F9/2 →6 H13/2 , and 4 F9/2 →6 H11/2 intraconfigurational transitions of Dy3+ ions, respectively. The evidence about the site symmetry around Dy3+ ions was examined by considering the ratio of yellow-to-blue emission intensity. The observed critical distance (Rc ) value was ~20.56 Å (≫5 Å), which signified that energy transfer primarily occurred due to multipolar interaction. The obtained coordinates were close to the white region of the Commission Internationale de l'Éclairage chromaticity diagram, which marked a significant milestone in the development of white light-emitting diodes.

Crystallographic, morphological and photoluminescent investigations of Tb3+ -doped YAlO3 perovskites for lighting applications.

Terbium(III)-doped yttrium aluminate perovskite (YAP:xTb3+ ) (x = 0.01-0.08 mol) was synthesized using a simple gel-combustion method. Structural elucidations were performed using X-ray diffraction (XRD) and Rietveld analysis. Fourier-transform infrared spectral studies validated the efficient synthesis of designed doped samples. Transmission electron microscopic images showed the agglomerated irregular dimensions of the synthesized nanocrystalline materials. When excited at 251 nm, a strong emissive line attributed to 5 D4 → 7 F5 electronic transition was observed at 545 nm (green emission). The maximum luminescence was found at the optimized concentration (0.05 mol) of Tb3+ ions; this emission was quenched by dipolar-dipolar (d-d) interactions. Chromaticity (x and y) and correlated colour temperature parameters were obtained by analysing the emission profiles. Finally, the colour coordinates of nanophosphors were closer to the National Television Standards Committee green coordinates, which replicates their potency in the design and architecture of R-G-B-based white LEDs.

Luminescent Features of Ternary Europium Complexes: Photophysical and Optoelectronic Evaluation.

Trivalent europium complexes exhibit good luminescent characteristics. A series of octacoordinated ternary europium complexes with fluorinated diketone and heteroaromatic auxiliary unit were synthesized. The synthesized europium complexes were characterized by elemental, thermal, electrochemical and spectroscopic analyses. Band gap values lie in range of semiconductors which confirm the conducting behavior of prepared complexes. Photoluminescence spectra were recorded in solid state and DMSO solvent. Emission spectral profiles have displayed most intense peak at ~ 612 nm corresponding to hypersensitive 5D0 → 7F2 transition. Colorimetric parameters suggest red luminous nature of europium complexes. The luminescent heteroleptic europium complexes might be utilized as emissive materials for fabricating display.

ß-Carotene-production methods, biosynthesis from Phaffia rhodozyma, factors affecting its production during fermentation, pharmacological properties: A review.

ß-Carotene is the most treasured provitamin A carotenoid molecule exhibiting antioxidant and coloring properties and significant applications in the food, pharmaceutical, and nutraceutical industries. ß-Carotene has many biological functions within the human body; however, it is not synthesized within the human body, so its requirements are fulfilled through food and pharmaceuticals. Its manufacturing via chemical synthesis or extraction from plants offers low yields with excessive manufacturing expenses, which attracted the researchers toward microbial production of ß-carotene. This alternative provides higher yield and low expenses and thus is more economical. Phaffia rhodozyma is a basidiomycetous yeast that is utilized to prevent cardiovascular diseases and cancer and to enhance immunity and antiaging in people. This paper reviews the methods of production of ß-carotene, biosynthesis of ß-carotene fromP. rhodozyma, factors affecting ß-carotene production during fermentation, and pharmacological properties of ß-carotene.

Luminous LaAlO3 :Dy3+ perovskite nanomaterials: Synthesis, structural, and luminescence characteristics for white light-emitting diodes.

A single-phase perovskite LaAlO3 :Dy3+ phosphor was synthesized using a gel-combustion method at 600°C utilization with hexamethylenetetramine as a fuel. Further calcination of the samples was carried out (800 and 1000°C) to investigate the resultant effect on the crystalline and luminescence behaviour. The crystal structure had a cubic unit cell (space group Pm3̅m) and was examined using the Rietveld refinement and X-ray diffraction data. Additionally, Debye-Scherrer and Williamson-Hall equations were applied to determine other structural features. The particle size and morphology of phosphors were evaluated using transmission electron microscopy. Diffraction measurements were supported by the various metal-oxygen vibration modes studied with the help of Fourier transform infrared spectroscopy. Energy-dispersive X-ray analysis verified the chemical composition of synthesized sample. Luminescence spectra of the LaAlO3 :Dy3+ phosphors exhibited intense bands for 4 F9/2 →6 H15/2 (482 nm, bluish region) and 4 F9/2 →6 H13/2 (574 nm, yellowish region) transitions. Commission Internationale de L'Eclairage and correlated colour temperature data confirmed the cool-white emission of the samples under ultraviolet light excitation. The interesting and advantageous luminescence characteristics of LaAlO3 :Dy3+ phosphors make them potential materials for white light-emitting diodes.

Emerging green light emission of Er3+ -activated single phased GdAlO3 phosphors for lighting applications.

An erbium ion (Er3+ )-activated gadolinium aluminate (GdAlO3 ) nanophosphor was synthesized by utilizing urea assisted gel-combustion method. The crystal structure along with all other crystal parameters was determined by X-ray diffraction (XRD) patterns. The selected samples are of orthorhombic phase with Pnma space group. The agglomerated particles within nanorange have been confirmed by transmission electron microscopy (TEM) micrographs. Elemental investigation was performed by energy dispersive X-ray spectroscopy (EDX). Photoluminescence excitation (PLE) spectrum reveals a strong excitation band corresponding to the gadolinium ion (Gd3+ ) (276 nm) and a band near ultraviolet (UV) absorption for Er3+ (377 nm). Strong excitation band of Gd3+ was evident for the energy transfer between Gd3+ and Er3+ ions. All the doped sampled are excited at 377 nm wavelength. The photoluminescence (PL) spectrum exhibits an intense band at 546 nm (4 S3/2 → 4 I15/2 ) which is responsible for the green emission in the processed samples. The color coordinate values define their color in the green region and correlated color temperature (CCT) values affirm their utility as a cold light source.

Spike sorting using non-volatile metal-oxide memristors.

Electrophysiological techniques have improved substantially over the past years to the point that neuroprosthetics applications are becoming viable. This evolution has been fuelled by the advancement of implantable microelectrode technologies that have followed their own version of Moore's scaling law. Similarly to electronics, however, excessive data-rates and strained power budgets require the development of more efficient computation paradigms for handling neural data in situ; in particular the computationally heavy task of events classification. Here, we demonstrate how the intrinsic analogue programmability of memristive devices can be exploited to perform spike-sorting on single devices. Leveraging the physical properties of nanoscale memristors allows us to demonstrate that these devices can capture enough information in neural signal for performing spike detection (shown previously) and spike sorting at no additional power cost.

In vivo ZW800-microbead imaging of retinal and choroidal vascular leakage in mice.

The eye is an attractive organ for non-invasive discovery and monitoring of disease progression. Traditionally, fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been used for dynamic evaluation of the retina and its vasculature. However, both fluorescein and indocyanine green (ICG) possess considerable disadvantages. FA is limited to assessing superficial retinal blood flow and often results in an unclear view due to fluorescein leakage. This obscures important pathologies such as neovascularization, ischemia and inflammation. ICG, a near-infrared fluorophore (NIRF), has nonspecific binding, high uptake and retention in tissues, as well as detrimental effects on the hepatobiliary tract. Here, we present a potential contrast agent for imaging ocular vascular permeability with ZW800, a heptamethine indocyanine NIRF, conjugated to polystyrene latex beads (ZW800m). ZW800 is an excellent alternative for near-infrared imaging, as it has excellent contrast, superior clearance, and is amendable to conjugation. ZW800m conjugation is an easy, attractive method of in vivo imaging and real-time tracking of ocular vascular pathologies. ZW800m is readily imaged via commercially available laser ophthalmoscope (SLO, HRA OCT, Spectralis) to assess vascular permeability in the mouse retina and choroid. In Type 1 diabetic Ins2Akita mice, ZW800m was observed in mouse retina but not in wild-type mice. After laser-induced choroidal neovascularization (CNV), ZW800m was observed in mouse choroid but not in control. In both CNV and diabetic mice, ZW800 imaging showed increased hyperfluorescence on ICG modality (ICGA) not seen on FA. Presence of ZW800m in respective tissues was confirmed ex vivo with flatmounts visualized with EVOS 800 nm light cube. ZW800 imaging may be easily employed in the research laboratory.

Pathophysiology and management of acute kidney injury in the setting of abdominal compartment syndrome.

Abdominal compartment syndrome (ACS) is defined as an organ dysfunction caused by intra-abdominal hypertension (IAH). Up to 4.2% of the patients in intensive care unit may develop IAH with it being an independent predictor of mortality. However, overall, it still remains a relatively underdiagnosed condition, part in because physical examination alone is very unreliable. Acute kidney injury is one of the most consistently described organ dysfunctions with oliguria being one of the earliest clinical signs of IAH. We recommend that any patient with evidence of new onset oliguria in the setting of distended abdomen, unexplained respiratory failure, with or without hypotension should be suspected of having IAH/ACS. Intravesicular pressure measurement represents a safe, rapid, and cost-effective method of diagnosing IAH. We hereby review the pathophysiology, diagnosis, and management of ACS and its association with acute kidney injury.

Effect of aggressively driven intravenous iron therapy on infectious complications in end-stage renal disease patients on maintenance hemodialysis.

For treating end-stage renal disease-associated anemia, various strategies to achieve optimal hemoglobin levels with lower erythropoiesis stimulating agent doses are being tried. One of these involves the use of a high dose [transferrin saturation (TSAT) >30%] of intravenous (IV) iron supplementation. However, due to in vitro effects of iron on stimulating bacterial growth, there are concerns of increased risk of infection. The safety of higher iron targets with respect to infectious complications (bacteremias, pneumonias, soft tissue infections, and osteomyelitis) is unknown. This was a retrospective study of patients on maintenance hemodialysis from a single, urban dialysis center to assess the long-term impact of the higher cumulative use of IV iron, on the incidence of clinically important infections. Our iron protocol was modified in June 2010 to aim for TSAT >30% unless serum ferritin levels were >1200 ng/mL. Data from only those patients who had been on dialysis for the whole duration between June 2009 and May 2011 were included. A total of 140 patients with end-stage renal disease on hemodialysis patients were found to be eligible for the study. There was a statistically significant increase in the mean TSAT and mean serum ferritin with the new anemia management protocol with a significant decrease in the mean erythropoiesis stimulating agent dose requirement. There was no statistically significant increase in the incidence of infectious complications. Although in vitro effects of iron are known to stimulate bacterial growth, a higher IV dose of iron may not increase the risk of infection in such patients.