Active Fluid Transport Research Articles

Cell-Driven Fluid Dynamics: A Physical Model of Active Systemic Circulation.

Active fluid circulation and transport are key functions of living organisms, which drive efficient delivery of oxygen and nutrients to various physiological compartments. Because fluid circulation occurs in a network, the systemic flux and pressure are not simple outcomes of any given component. Rather, they are emergent properties of network elements and network topology. Moreover, consistent pressure and osmolarity gradients across compartments such as the kidney, interstitium, and vessels are known. How these gradients and network properties are established and maintained is an unanswered question in systems physiology. Previous studies have shown that epithelial cells are fluid pumps that actively generate pressure and osmolarity gradients. Polarization and activity of ion exchangers that drive fluid flux in epithelial cells are affected by pressure and osmolarity gradients. Therefore, there is an unexplored coupling between the pressure and osmolarity in the circulating network. Here we develop a mathematical theory that integrates the influence of pressure and osmolarity on solute transport and explores both cell fluid transport and systemic circulation. This model naturally generates pressure and osmolarity gradients across physiological compartments, and demonstrates how systemic transport properties can depend on cell properties, and how the cell state can depend on systemic properties. When epithelial and endothelial pumps are considered together, we predict how pressures at various points in the network depend on the overall osmolarity of the system. The model can be improved by including physiological geometries and expanding solute species, and highlights the interplay of fluid properties with cell function in living organisms.

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury.

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model. Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na + -K + -ATPase activity was assessed using enzyme-linked immunosorbent assay. Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na + -K + -ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1β; increased the expression of AQP-1, AQP-5, αENaC, and βENaC; and increased Na + -K + -ATPase activity. Moreover, the regulation of AQPs, βENaC, and Na + -K + -ATPase and the inhibition of TNF-α and IL-1β by TFENF were found to be dose dependent. Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na + -K + -ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.

English

BACKGROUND Chronic kidney disease (CKD) encloses a continuum of pathophysiological processes associated with deranged kidney function and a progressive decrease in glomerular filtration rate (GFR). There are many anatomic similitudes between cochlea and kidney at an ultra-structural level and antigenic level along with comparable physiological mechanisms, specifically, the active fluid and electrolytes transport in the cochlea and the kidney. The purpose of the present study was to determine the proportion, type and degree of hearing loss in patients with renal disease and its comparison according to the stage of CKD. METHODS The study was conducted on 60 patients of chronic kidney disease labelled as stage 3, 4 and 5 on the basis of GFR. An audiogram charted by pure tone audiometry was used to find the degree of hearing loss and its comparison in patients with moderate, severe and end stage CKD was done. The data was collected and analysed statistically. RESULTS The mean age of patients was 55.58 +/- 11.36 years and the mean duration of CKD was 15.61 months. 90 % patients of CKD had sensorineural hearing loss while 10 % had hearing sensitivity within normal limits. In the present study, mild degree hearing loss and high frequency hearing loss was found to be predominant constituting 68.3 % (n = 41) and 58.3 % (n = 35) respectively. Mild degree of hearing loss was a predominant finding irrespective of the stage and duration of CKD. CONCLUSIONS Sensorineural hearing loss was found predominantly amongst the CKD patients in our study population. Mild degree hearing loss was predominant but there was no correlation between stage of CKD and degree of hearing loss. While there was a significant correlation between degree of hearing loss with duration and haemodialysis amongst the non-diabetic CKD patients. KEYWORDS Chronic Kidney Disease, Sensorineural Hearing Loss

Hypotheses about sub-optimal hydration in the weeks before coronavirus disease (COVID-19) as a risk factor for dying from COVID-19

To address urgent need for strategies to limit mortality from coronavirus disease 2019 (COVID-19), this review describes experimental, clinical and epidemiological evidence that suggests that chronic sub-optimal hydration in the weeks before infection might increase risk of COVID-19 mortality in multiple ways. Sub-optimal hydration is associated with key risk factors for COVID-19 mortality, including older age, male sex, race-ethnicity and chronic disease. Chronic hypertonicity, total body water deficit and/or hypovolemia cause multiple intracellular and/or physiologic adaptations that preferentially retain body water and favor positive total body water balance when challenged by infection. Via effects on serum/glucocorticoid-regulated kinase 1 (SGK1) signaling, aldosterone, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), aquaporin 5 (AQP5) and/or Na+/K+-ATPase, chronic sub-optimal hydration in the weeks before exposure to COVID-19 may conceivably result in: greater abundance of angiotensin converting enzyme 2 (ACE2) receptors in the lung, which increases likelihood of COVID-19 infection, lung epithelial cells which are pre-set for exaggerated immune response, increased capacity for capillary leakage of fluid into the airway space, and/or reduced capacity for both passive and active transport of fluid out of the airways. The hypothesized hydration effects suggest hypotheses regarding strategies for COVID-19 risk reduction, such as public health recommendations to increase intake of drinking water, hydration screening alongside COVID-19 testing, and treatment tailored to the pre-infection hydration condition. Hydration may link risk factors and pathways in a unified mechanism for COVID-19 mortality. Attention to hydration holds potential to reduce COVID-19 mortality and disparities via at least 5 pathways simultaneously.

Active interfacial dynamic transport of fluid in a network of fibrous connective tissues throughout the whole body.

Fluid in interstitial spaces accounts for ~20% of an adult body weight and flows diffusively for a short range. Does it circulate around the body like vascular circulations? This bold conjecture has been debated for decades. As a conventional physiological concept, interstitial space is a micron‐sized space between cells and vasculature. Fluid in interstitial spaces is thought to be entrapped within interstitial matrix. However, our serial data have further defined a second space in interstitium that is a nanosized interfacial transport zone on a solid surface. Within this fine space, fluid along a solid fibre can be transported under a driving power and identically, interstitial fluid transport can be visualized by tracking the oriented fibres. Since 2006, our data from volunteers and cadavers have revealed a long‐distance extravascular pathway for interstitial fluid flow, comprising at least four types of anatomic distributions. The framework of each extravascular pathway contains the longitudinally assembled and oriented fibres, working as a fibrorail for fluid flow. Interestingly, our data showed that the movement of fluid in a fibrous pathway is in response to a dynamic driving source and named as dynamotaxis. By analysis of previous studies and our experimental results, a hypothesis of interstitial fluid circulatory system is proposed.

Microscopic anatomy of ocular globe in diurnal desert rodent Psammomys obesus (Cretzschmar, 1828)

BackgroundThe visual system of desert rodents demonstrates a rather high degree of development and specific features associated with adaptation to arid environment. The aim of this study is to carry out a descriptive investigation into the most relevant features of the sand rat eye.ResultsLight microscopic observations revealed that the eye of Psammomys obesus diurnal species, appears similar to that of others rodent with characteristic mammalian organization. The eye was formed by the three distinct layers typical in vertebrates: fibrous tunic (sclera and cornea); vascular tunic (Iris, Ciliary body, Choroid); nervous tunic (retina). Three chambers of fluid fundamentals in maintaining the eyeball’s normal size and shape: Anterior chamber (between cornea and iris), Posterior chamber (between iris, zonule fibers and lens) and the Vitreous chamber (between the lens and the retina) The first two chambers are filled with aqueous humor whereas the vitreous chamber is filled with a more viscous fluid, the vitreous humor. These fluids are made up of 99.9% water. However, the main features, related to life style and arid environment, are the egg-shaped lens, the heavy pigmentation of the middle layer and an extensive folding of ciliary processes, thus developing a large surface area, for ultrafiltration and active fluid transport, this being the actual site of aqueous production. The ciliary muscle is poorly developed and the dilator pupillae is not apparent.ConclusionsThe ocular globe of sand rat demonstrates a high degree of development and several specific features associated with adaptation to life style and arid environment.

Amyloid-β and Parkinson's disease.

Parkinson's disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation of misfolded α-synuclein is considered to be a key underpinning mechanism. Amyloid-β (Aβ) and tau deposition are also comorbid associations and especially Aβ deposition is associated with cognitive decline in PD. Some existing evidence suggests that low cerebrospinal fluid (CSF) Aβ42 is predictive of future cognitive impairment in PD. Recent studies also show that CSF Aβ is associated with the postural instability and gait difficulties (PIGD) or the newly proposed cholinergic subtype of PD, a possible risk factor for cognitive decline in PD. The glial-lymphatic system, responsible for convective solute clearance driven by active fluid transport through aquaporin-4 water channels, may be implicated in brain amyloid deposition. A better understanding of the role of this system and more specifically the role of Aβ in PD symptomatology, could introduce new treatment and repurposing drug-based strategies. For instance, apomorphine infusion has been shown to promote the degradation of Aβ in rodent models. This is further supported in a post-mortem study in PD patients although clinical implications are unclear. In this review, we address the clinical implication of cerebral Aβ deposition in PD and elaborate on its metabolism, its role in cognition and motor function/gait, and finally assess the potential effect of apomorphine on Aβ deposition in PD.

Specialized Pro-resolving Mediators Regulate Alveolar Fluid Clearance during Acute Respiratory Distress Syndrome.

Objective:Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS.Data Sources:Articles published up to September 2017 were selected from the PubMed, with the keywords of “alveolar fluid clearance” or “lung edema” or “acute lung injury” or “acute respiratory distress syndrome”, and “specialized pro-resolving mediators” or “lipoxin” or “resolvin” or “protectin” or “maresin” or “alveolar epithelial cells” or “aspirin-triggered lipid mediators” or “carbon monoxide and heme oxygenase” or “annexin A1”.Study Selection:We included all relevant articles published up to September 2017, with no limitation of study design.Results:Specialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.Conclusions:The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design “reabsorption-targeted” therapies with high degrees of precision in controlling ALI/ARDS.

The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?

How solutes and macromolecules are removed from brain tissue is of central importance in normal brain physiology and in how toxic protein aggregates are cleared in neurodegenerative conditions, including Alzheimer's disease (AD). Conventionally, solute transport in the narrow and tortuous extracellular space in brain parenchyma has been thought to be primarily diffusive and nondirectional. The recently proposed "glymphatic" (glial-lymphatic) hypothesis posits that solute clearance is convective and driven by active fluid transport from para-arterial to paravenous spaces though aquaporin-4 water channels in astrocyte endfeet. Glymphatic, convective solute clearance has received much attention because of its broad implications for AD and other brain pathologies and even the function of sleep. However, the theoretical plausibility of glymphatic transport has been questioned, and recent data have challenged its experimental underpinnings. A substantiated mechanism of solute clearance in the brain is of considerable importance because of its implications for pathogenic mechanisms of neurologic diseases and delivery of therapeutics.-Smith, A. J., Verkman, A. S. The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?

Artificial Cilia for Capture and Sampling

There is a need for improved methods of pre-concentration and detection of bacteria in food safety. The sample preparation is necessary to increase the number of target bacteria in a fluid sample to improve the limit of detection. We show the use of metallic thin films as artificial cilia for applications in sample manipulation in microfluidics and biosensors. We use evaporated alloy of nickel-iron on a glass substrate which are actuated magnetically by varying the external magnetic field. These hair like synthetic structures actuated by the magnetic field have a highly asymmetric bending patterns in an oscillatory cycle. This asymmetry is important for creating any microfluidic transport. In this work, we exploit this asymmetry in the strokes and demonstrate microfluidic transport phenomenon of pumping, rapid mixing and capture of micro-particles in a microchannel. To characterize the microfluidic pumping capabilities of the artificial cilia, we incorporate the cilia inside a PDMS microchannel loop and analyze the flow in produces. We vary important parameters such as the cilia width, spacing, number of rows and channel dimensions and establish its influence on the pumping efficiency. We observe low pumping rates at very high and very low operating frequencies, and establish an optimum operating frequency for maximized pumping efficiency. Further, we demonstrate the use of such cilia for microfluidic mixing. For this, we use a PDMS Y-channel with cilia on its bottom wall. Two fluids dyed with different fluorescent colors are introduced into the two inlet channels. And the ability of the cilia to mix the two streams of fluid is characterized by imaging the fluorescent intensity of the fluid stream downstream from the cilia. Again, we show the dependence of mixing efficiency on several parameters of the system. We also demonstrate particle capture with these artificial cilia. To do this, we functionalize the cilia with streptavidin protein, and introduce particles coated with biotin into the microchannel. The cilia is then oscillated so as to produce mixing in the microchannel. The mixing effect increases the probability of particles coming in contact with the cilia. The biotin coated particles stick to the cilia when they come into contact. This demonstrates capture of particles in a microfluidic channel. These microfluidic functions find varied application in many lab on a chip devices where active fluid transport is needed.

Ethanol fermentation bioreactor for microfluidic actuation

We present a concept for autonomous, long-term and high-pressure fluid transport on microfluidic chips, which is fully bio-compatible and, in principle, also compostable. The actuation principle is based on ethanol fermentation, a well-known biological process in which microorganisms such as yeast cells convert sugar molecules into cellular energy and thereby produce ethanol and carbon dioxide (CO2) as metabolic waste products. A two-chamber fluidic system separated by a flexible membrane is proposed for active fluid transport utilizing a bio-reactor. One chamber, connected to the outside via a pressure-sensitive valve, contains the fluid to be actuated, the other one the culture medium for the yeast cells. Once the yeast cells are injected into the culture medium, ethanol fermentation and thus the production of CO2 starts, which builds up pressure on the membrane and hence also on the fluid chamber. As soon as the switching point of the pressure sensitive valve is reached, fluid transport at a predefined and constant flow rate starts.

Ethanol Fermentation as the Basis for Autonomous, Long-term and High-pressure Fluid Transport in Microfluidics

We present a concept for autonomous, long-term and high-pressure fluid transport on disposable microfluidic chips, which are fully bio-compatible and compostable. The actuation principle is based on ethanol fermentation, a well-known biological process in which yeast cells convert molecules like sucrose into cellular energy and thereby produce ethanol and carbon dioxide (CO2) as metabolic waste products. A two-chamber fluidic system separated by a flexible membrane is suggested for active fluid transport utilizing a bio-reactor. One chamber, connected to the outside via a pressure-sensitive valve, contains the fluid to be actuated, the other one the culture medium for the yeast cells. Once the yeast cells are injected into the culture medium, ethanol fermentation and thus the production of CO2 starts, which builds up pressure on the membrane and hence also on the fluid chamber. As soon as the switching point of the pressure sensitive valve is reached, fluid transport at a predefined and constant flow rate starts.

Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume.

Pathophysiology of Neonatal Transition and Meaningful Measures for the Initial Stabilisation of Extremely Premature Neonates

This report discusses the physiological aspects of neonatal transition from breathing liquid to air. Further, we discuss reasonable medical interventions to actively assist a gentle transition, and focus on team aspects of preparing both the perinatal team and parents for the challenging situation of preterm labour and delivery. Our aim is to critically evaluate current concepts on the physiology of neonatal transition and the current assessment of the newborn infant, to present means to facilitate non-traumatic pulmonary aeration and ways to foster successful teamwork and professional parental guidance in the delivery room. The authors report on their own work and on that of other research groups, as recently published in peer reviewed medical journals. When born, the newborn needs to rapidly clear his/her lungs from fluid to establish breathing. Active fluid transport and passive resorption help to establish the pulmonary functional residual capacity (FRC). Prenatal administration of corticosteroids helps to form and maintain the FRC of the newborn. Many very low gestational age neonates (ELGAN) will breathe at birth but require medical assistance. This is best done by giving distending positive airway pressure at levels of 5 cmH(2)O, or greater. Monitoring of these infants should be by peripheral pulse oximetry. Some ELGANs may require non-invasive ventilation and/or exogenous Surfactant replacement, and even fewer may require intubation and mechanical ventilation. The obstetric and neonatal teams need to coordinate their joined efforts to secure a safe delivery for mother and child. Ways of communication between teams and parents are presented. Many neonatal teams use video recording as a tool to assess and improve their work. We give insights into the use of video as a means to improve teamwork and patient care alike.

Effective tension and fluctuations in active membranes

We calculate the fluctuation spectrum of the shape of a lipid vesicle or cell exposed to a nonthermal source of noise. In particular, we take constraints on the membrane area and the volume of fluid that it encapsulates into account when obtaining expressions for the dependency of the membrane tension on the noise. We then investigate three possible origins of the nonthermal noise taken from the literature: A direct force, which models an external medium pushing on the membrane, a curvature force, which models a fluctuating spontaneous curvature, and a permeation force coming from an active transport of fluid through the membrane. For the direct force and curvature force cases, we compare our results to existing experiments on active membranes.

Cell signaling in regulation of the barrier integrity of the corneal endothelium

The barrier integrity of the corneal endothelium, which is conferred by its tight and adherens junctions, is critical for the maintenance of deturgescence of the corneal stroma. Although characteristically leaky, the barrier integrity restricts fluid leakage into the stroma such that the rate of leak does not exceed the rate of the endothelial active fluid transport directed toward the aqueous humor. At a molecular level, the barrier integrity is influenced by the actin cytoskeleton and microtubules, which are coupled to tight and adherens junctions via a variety of linker proteins. Since the cytoskeleton is affected by Rho family small GTPases and p38 MAP kinase, among others, many pathophysiological stimuli induce plasticity to the cytoskeleton and thereby elicit dynamic regulation of the barrier integrity. This review presents an overview of the impact of several bioactive factors on the barrier integrity of the corneal endothelium through altered actin cytoskeleton and/or disassembly of microtubules. The main focus is on the effect of TNF-α (tumor necrosis factor-α) which is a pro-inflammatory molecule found in the intraocular milieu during allograft rejection and anterior uveitis. This cytokine elicits acute activation of p38 MAP kinase, induces disassembly of microtubules, disrupts the peri-junctional actomyosin ring, and concomitantly breaks down the barrier integrity. These effects of TNF-α could be inhibited by stabilizing the microtubules, co-treating with a selective p38 MAP kinase inhibitor, and elevating intracellular cAMP via A2B receptors or direct exposure to forskolin. Overall, the corneal edema following a potential breakdown of the endothelial barrier integrity can be rescued pharmacologically by inhibiting specific cell-signaling mechanisms.

Aquaporins at a glance

With a concentration of 55,000 mM, water is by far the most prevalent molecule in biological systems. For many years it was assumed that biological membranes are freely water permeable, so that the existence of a family of water channels would not have been predicted. However, biophysical studies in

A Sigh of Relief About Treating Influenza in Individuals With Alcohol-Use Disorders?

The recent outbreak of so-called “swine flu,” or influenza caused by an H1N1 strain of the influenza A virus, has renewed the public fear (as well as within the medical community) about pandemic influenza. However, we must all remember that seasonal epidemic influenza has always been a serious public health concern. For example, an average of more than 41,000 per year died of influenza in the United States alone between 1979 and 2001 (Dushoff et al., 2006). Although annual vaccinations remain the foundation of public health efforts to limit the severity of seasonal epidemics, many unvaccinated individuals are either exposed to the virus or present with frank influenza illness and are treated with neuraminidase inhibitors such as oseltamivir (trade name Tamiflu) to reduce symptoms and/or transmission of the virus (Moscona, 2005). Although it has long been known that individuals with chronic alcohol-use disorders are at increased risk of a wide variety of community-acquired lung infections, there are no specific studies that have examined the role of alcohol-use disorders on the risks of acquiring and/or spreading influenza. However, studies in animal models have raised concerns; in particular, a study by Legge and colleagues showed that chronic alcohol consumption increased the mortality of influenza infection in a murine model (Meyerholz et al., 2008). In parallel, our group has shown that chronic alcohol ingestion increases the severity of acute edematous lung injury by impairing the normal epithelial barrier in the lung and placing an increased burden on the active transport of sodium and water from the airways to keep the airspaces dry (Guidot et al., 2000; Otis et al., 2008). In parallel, we also determined that the influenza virus interferes with this active fluid transport in the lung (Chen et al., 2004). Taken together, these experimental findings suggest that even otherwise healthy individuals with a chronic alcohol-use disorder could be at increased risk of acute edematous lung injury and death from influenza. Unfortunately, these subjects are also less likely to receive annual vaccinations, and therefore, their survival could depend on the ability of drugs such as oseltamivir to limit the acute illness. In this regard, the findings by Legge and colleagues (Langlois et al.) in the current issue provide some cautious optimism from their murine model that, at least in otherwise healthy subjects with underlying chronic alcohol use, oseltamivir might remain effective in limiting the severity of acute influenza illness. Specifically, mice given ethanol for 8 weeks in their drinking water and then inoculated with influenza virus had a 60% mortality when compared to a 15% mortality in control mice. In contrast, oseltamivir treatment markedly decreased morbidity and completely prevented any mortality in both control and ethanol-treated mice. Consistent with the elimination of mortality, oseltamivir decreased viral shedding and lung inflammation in both groups. Although one must obviously interpret these experimental findings cautiously, this study suggests that neuraminidase inhibitors retain their ability to limit the severity of acute influenza pneumonia even in the context of chronic alcohol ingestion. Although it appears for now that the extent and severity of the current H1N1 epidemic has been far less than initially feared, public health officials and clinicians can never drop their guard as epidemic seasonal influenza and intermittent (and unpredictable) pandemics are inevitable. For now, this new study suggests we can remain hopeful that antiviral drugs used to limit the spread of influenza in unvaccinated individuals will retain their efficacy even for those who suffer from chronic alcohol-use disorders.

Precursor and Solvent Effects in the Nonhydrolytic Synthesis of Complex Oxide Nanoparticles for Bioimaging Applications by the Ether Elimination (Bradley) Reaction

Investigation of the solvent and alkoxide precursor effect on the nonhydrolytic sol-gel synthesis of oxide nanoparticles by means of an ether elimination (Bradley) reaction indicates that the best crystallinity of the resulting oxide particles is achieved on application of aprotic ketone solvents, such as acetophenone, and of smallest possible alkoxide groups. The size of the produced primary particles is always about 5 nm caused by intrinsic mechanisms of their formation. The produced particles, possessing the composition of natural highly insoluble minerals, are biocompatible. Optical characteristics of the perovskite complex oxide nanoparticles can easily be controlled through doping with rare earth cations; for example, by Eu(3+). They can be targeted through surface modification by anchoring the directing biomolecules through a phosphate or phosphonate moiety. Testing of the distribution of Eu-doped BaTiO(3) particles, modified with ethylphosphonic acid, demonstrates their facile uptake by the plants with active fluid transport, resulting finally in their enhanced concentration within the cell membranes.

Pulmonary Complications After Acute Kidney Injury

The development of respiratory failure in patients with AKI is a particularly devastating consequence that greatly increases patient mortality. When respiratory failure and AKI occur together, the mortality is greater than 80%. A clear understanding of the mechanisms leading to respiratory failure is of great clinical relevance to patients with AKI in order to prevent and treat this life-threatening complication. Pulmonary edema leading to respiratory failure has been a recognized complication of kidney failure since 1901. Remarkably, the pathogenesis of this complication remains elusive, despite over 100 years of clinical and experimental debate in the literature. A review of this literature suggests that there are 4 causes of pulmonary edema leading to respiratory failure in patients with AKI: (1) volume overload (cardiogenic edema), (2) left ventricular dysfunction (cardiogenic edema), (3) increased lung capillary permeability (noncardiogenic edema), and (4) acute lung injury (noncardiogenic edema with inflammation). In this review, these mechanisms are presented in historical context including the original descriptions of pathology and pathophysiology, recent epidemiologic data, and experimental studies in animals. Although volume overload is a well-accepted mechanism of pulmonary edema in patients with AKI, the purpose of this review was to highlight the evidence showing that noncardiogenic edema and acute lung injury also occur. By recognizing that the pulmonary complications of AKI are not simply from volume overload, specific treatment strategies may be discovered and used to improve outcomes in patients with the ominous and life threatening combination of AKI and respiratory failure.