Low doses of ionizing radiation and circulatory diseases: a systematic review of the published epidemiological evidence

Recent analyses of mortality among atomic bomb survivors have suggested a linear dose-response relationship between ionizing radiation and diseases of the circulatory system for exposures in the range 0-4 Sv. If confirmed, this has substantial implications. We have therefore reviewed the published literature to see if other epidemiological data support this finding. Other studies allowing a comparison of the rates of circulatory disease in individuals drawn from the same population but exposed to ionizing radiation at different levels within the range 0-5 Gy or 0-5 Sv were identified through systematic literature searches. Twenty-six studies were identified. In some, disease rates among those exposed at different levels may have differed for reasons unrelated to radiation exposure, while many had low power to detect effects of the relevant magnitude. Among the remainder, one study found appreciable evidence that exposure to low-dose radiation was associated with circulatory diseases, but five others, all with appreciable power, did not. We conclude that the other epidemiological data do not at present provide clear evidence of a risk of circulatory diseases at doses of ionizing radiation in the range 0-4 Sv, as suggested by the atomic bomb survivors. Further evidence is needed to characterize the possible risk.     

INTRACORPOREAL HEAT DISSIPATION FROM A RADIOISOTOPE-POWERED ARTIFICIAL HEART

The feasibility of radioisotope-fueled circulatory support systems depends on the ability of the body to dissipate the reject heat from the power source driving the blood pump as well as to tolerate chronic intracorporeal radiation. Our studies have focused on the use of the circulating blood as a heat sink. Initial in vivo heat transfer studies utilized straight tube heat exchangers (electrically and radioisotope energized) to replace a segment of the descending aorta. More recent studies have used a left ventricular assist pump as a blood-cooled heat exchanger. This approach minimizes trauma, does not increase the area of prosthetic interface with the blood, and minimizes system volume. Heat rejected from the thermal engine (vapor or gas cycle) is transported from the nuclear power source in the abdomen to the pump in the thoracic cavity via hydraulic lines. Adjacent tissue is protected from the fuel capsule temperature (900 to 1200 degrees F) by vacuum foil insulation and polyurethane foam. The in vivo thermal management problems have been studied using a simulated thermal system (STS) which approximates the heat rejection and thermal transport mechanisms of the nuclear circulatory support systems under development by NHLI. Electric heaters simulate the reject heat from the thermal engines. These studies have been essential in establishing the location, suspension, surgical procedures, and postoperative care for implanting prototype nuclear heart assist systems in calves. The pump has a thermal impedance of 0.12 degrees C/watt. Analysis of the STS data in terms of an electrical analog model implies a heat transfer coefficient of 4.7 x 10(-3) watt/cm(2) degrees C in the abdomen compared to a value of 14.9 x 10(-3) watt/cm(2) degrees C from the heat exchanger plenum into the diaphragm.     

A glucose fuel cell for implantable brain-machine interfaces

We have developed an implantable fuel cell that generates power through glucose oxidation, producing 3.4 μW cm(-2) steady-state power and up to 180 μW cm(-2) peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain-machine interfaces can thus potentially benefit from having their implanted units powered or recharged by glucose fuel cells.     

Pathways for metabolic fuels and oxygen in high performance fish

This paper gives an overview of oxidative fuel metabolism in swimming fish, and known or potential modifications occurring in high-performance species are explored. Carbohydrate catabolism is the only source of ATP for sprint swimming where locomotory muscles operate as closed systems. In contrast, this substrate only plays a very minor role in prolonged swimming. Glucose fluxes have been measured in vivo in several species, but mainly at rest and with somewhat questionable methodologies. High-performance species may be able to sustain higher maximal glucose fluxes that their sedentary counterparts by: a) upregulating gluconeogenesis, b) increasing glucose transporter density or V_max of individual transporters, c) storing larger amounts of glycogen in liver and muscle, and d) increasing muscle hexokinase activity. Even though lipids represent a much more important source of energy for sustained swimming, their fluxes have not been measured in vivo, even at rest, probably because of their diversity and complex chemistry. Except for elasmobranchs who do not possess plasma proteins for lipid transport, high-performance fish should be able to sustain high maximal lipid fluxes by: a) elevating lipolytic capacity, b) increasing rates of circulatory lipid transport through modified plasma proteins, c) augmenting intramuscular lipid reserves, and d) upregulating capacity for lipid oxidation in locomotory muscle mitochondria. The quantitative assessment of amino acid oxidation in swimming fish is a priority for future research because protein is probably a dominant metabolic fuel in most swimming fish. Finally, we predict that high-performance species should use proportionately more proteins/lipids and less carbohydrates than low-aerobic fish. Also, and similarly to endurance-adapted mammals, high-performance fish should increase their relative reliance on intramuscular fuel reserves and decrease their relative use of circulatory fuels.     

Aminopeptidase activity in the hemolymph and body tissues of the pulmonate gastropod Biomphalaria glabrata

The levels of aminopeptidase activity in the whole hemolymph, serum, hemocytes, headfoot, and visceral mass of Biomphalaria glabrata were determined. The highest enzyme level occurs in the serum and the lowest in the hemocytes. Both the headfoot and visceral mass include subequal levels of aminopeptidase activity. From our data, it now appears possible that the serum aminopeptidase in B. glabrata, which has an open circulatory system, could have originated in hemocytes as well as in other tissues. The biologic function of serum aminopeptides is uncertain; however, because of the known chemical function of this enzyme, it could serve to degrade foreign proteins in serum prior to phagocytosis.     

An “ancient” complexity? Evolutionary morphology of the circulatory system in Xiphosura

Horseshoe crabs (Xiphosura) have been an object of zoological research for almost 200 years. Although some morphological work on the circulatory system has been done, the three-dimensional structure of this complex organ system has never been shown satisfactorily and some crucial questions remain unanswered. Here, the circulatory systems of juveniles of the horseshoe crab taxa Limulus polyphemus and Carcinoscorpius rotundicauda were investigated using a combination of an injection method and micro-computed tomography. Data were processed and 3D-visualized using reconstruction software. Furthermore, the heart was examined using scanning electron microscopy. Additionally, the histology of some structures was investigated via light microscopy and transmission electron microscopy. The results show the high degree of complexity of the arterial and lacunar systems of Xiphosura and provide insights into their three-dimensional structure and relationship to other organ systems such as the central nervous system. We show that the major lacunae, previously described as vessel-like – though indeed highly ramified – can clearly be distinguished from arteries in histological sections because they have no distinct walls. Similarities and differences between the xiphosuran species and arachnids are highlighted and possible phylogenetic implications and evolutionary scenarios discussed.     

The circulatory system in Phreatoicidea: implications for the isopod ground pattern and peracarid phylogeny

The circulatory systems of four species of Phreatoicidea and two species of Oniscidea were studied on the basis of serial semi-thin sections and a corrosion cast method. A 3D computer reconstruction was used to visualize the circulatory organs in the head of the Phreatoicidea. In the Phreatoicidea, the circulatory system consists of a longitudinal dorsal heart extending from the third thoracic to the border between the fourth and fifth pleonal segments. It is equipped with two pairs of asymmetrically arranged ostia, while five pairs of lateral cardiac arteries and an unpaired anterior aorta extend from the heart. Entering the head, the aorta is accompanied by the two first lateral arteries, which supply the muscles of the mandibles. Four pairs of arteries branch off the aorta to supply both pairs of antennae, the eyes, and sinuses in the head. In addition, several minute capillaries extend from the aorta to supply the brain. The two oniscidean species were re-investigated with regard to some characters which have been controversially discussed. In these species, the heart extends from the border between the fifth and sixth thoracic segments to the fifth pleonal segment. Five pairs of lateral cardiac arteries and the unpaired anterior aorta lead off the heart. A ventral vessel was not observed. The ground pattern of the circulatory system in isopods is reconstructed with greater reliability through optimisation of its characters based on proposed phylogenetic relationships. The results do not support a phylogenetic position of the Isopoda as basal Peracarida or even basal Eumalacostraca.     

Tissue engineering of a bioartificial kidney

Tissue engineering is a rapidly growing field in biotechnology. The use and packaging of synthetic materials, biologic compounds, and cellular components of specific tissues can be envisioned to replace physiologic function of diseased organs. Long-term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. The initial concepts for these devices are just beginning to be considered and developed. (c) 1994 John Wiley & Sons, Inc.     

Intrinsically Stretchable Fuel Cell Based on Enokitake‐Like Standing Gold Nanowires

Conventional fuel cells are based on rigid electrodes, limiting their applications in wearable and implantable electronics. Here, it is demonstrated that enokitake‐like vertically‐aligned standing gold nanowires (v‐AuNWs) can also serve as powerful platform for stretchable fuel cells by using ethanol as model system. Unlike traditional fuel cell electrodes, the v‐AuNWs have “Janus Morphology” on both sides of the film and also are highly stretchable. The comparative studies demonstrate that tail side exposed v‐AuNWs based stretchable electrodes outperform the head‐side exposed v‐AuNWs toward the electro‐oxidation of ethanol due to the direct exposure of high‐surface‐area nanowires to the fuels. Therefore, a stretchable fuel cell is fabricated utilizing tail side based interdigitated electrodes, where v‐AuNWs and Pt black modified v‐AuNWs serve as the anode and cathode, respectively. The as‐prepared stretchable fuel cell exhibits good overall performance, including high power density, current density, open‐circuit voltage, stretchability, and durability. Most importantly, a wearable fuel cell is also achieved by integrating tattoo‐like interdigitated electrodes with a thin layer of sponge as a fuel container, exhibiting good performance under various deformations (compression, stretching, and twisting). Such attractive performance in conjunction with skin‐like in‐plane design indicates its great potential to power the next‐generation of wearable and implantable devices.     

Should all patients receive dual chamber pacing ICDs? The rationale for the DAVID trial

All of the prospective multicenter trials that support the use of implantable defibrillators have used single chamber pacemakers/implantable cardiovertor defibrillators (ICDs). Despite the significantly increased cost of dual chamber pacemaker/ICD devices and the lack of outcome data, these devices accounted for approximately two-thirds of the ICDs implanted in the United States during the 12 months ending April 2001. Dual chamber pacemaker trials have not provided data that would support this trend, but the high incidence of atrial fibrillation, bradycardia, and congestive heart failure, as comorbid conditions, suggest that the situation could be different in the defibrillator patient population. The DAVID (Dual Chamber and VVI Implantable Defibrillator) trial is designed to measure the incremental benefit of dual chamber pacemaker/ICDs.     

Proteomic characterization of skin and epidermis in response to environmental agents

The skin and its outer epidermis layer in particular, prevent access of various environmental agents including potential allergens, irritants, carcinogens, ultraviolet radiation and microbes. Cells in the epidermis make a significant contribution to innate as well as adaptive immune reactions in skin. The skin immunity thus provides a biologic defense in response to hazardous environmental agents. Although proteomics has been utilized to establish skin proteomes and investigate skin responses to some environmental agents, it has not been extensively used to address the complexity of skin responses to various environments. This review summarizes cutaneous genes and proteins that have been characterized as related to skin exposure to environmental agents. In parallel, this review emphasizes functional proteomics and systems biology, which are believed to be an important future direction toward characterizing the skin proteome–environmental interaction and developing successful therapeutic strategies for skin diseases caused by environmental insults.     

Thiol/disulfide redox states in signaling and sensing

Abstract

Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol–disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol–disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities.     

Proteomic characterization of skin and epidermis in response to environmental agents

The skin and its outer epidermis layer in particular, prevent access of various environmental agents including potential allergens, irritants, carcinogens, ultraviolet radiation and microbes. Cells in the epidermis make a significant contribution to innate as well as adaptive immune reactions in skin. The skin immunity thus provides a biologic defense in response to hazardous environmental agents. Although proteomics has been utilized to establish skin proteomes and investigate skin responses to some environmental agents, it has not been extensively used to address the complexity of skin responses to various environments. This review summarizes cutaneous genes and proteins that have been characterized as related to skin exposure to environmental agents. In parallel, this review emphasizes functional proteomics and systems biology, which are believed to be an important future direction toward characterizing the skin proteome-environmental interaction and developing successful therapeutic strategies for skin diseases caused by environmental insults.     

BIOCHEMICAL, HEMATOLOGIC AND COAGULATION VALUES IN THE HEREFORD CALF

Biochemical, hematologic and coagulation values have been determined in normal Hereford calves of both sexes, two to six months of age. These data generally agree with those of others and indicate a similarity in calves irrespective of their age, sex or breed. Prothrombin times are markedly longer in the calf than in man. This has resulted in alterations of anticoagulation regimens after implantation of mechanical circulatory support systems.     

Experimental verification of the method for detection of water microleakages in plasma vacuum chambers by using the hydroxyl spectrum

Experimental determination of the sensitivity of the method for detection of water microleakages in the cooling systems of the plasma vacuum chambers of complex electrophysical devices (such as tokamaks, fuel elements of nuclear reactors, and plasmachemical reactors) is considered. It was shown that the spectroscopic method for detection of water microleakages by using the hydroxyl radiation spectrum makes it possible to detect leakages at a level of 10⁻⁵ Pa m³ s⁻¹. The spatial resolution of the method allows one to localize defects with an accuracy of several centimeters.     

Tissue biomarkers for prostate cancer radiation therapy

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.     

The optical stretcher: a novel laser tool to micromanipulate cells.

When a dielectric object is placed between two opposed, nonfocused laser beams, the total force acting on the object is zero but the surface forces are additive, thus leading to a stretching of the object along the axis of the beams. Using this principle, we have constructed a device, called an optical stretcher, that can be used to measure the viscoelastic properties of dielectric materials, including biologic materials such as cells, with the sensitivity necessary to distinguish even between different individual cytoskeletal phenotypes. We have successfully used the optical stretcher to deform human erythrocytes and mouse fibroblasts. In the optical stretcher, no focusing is required, thus radiation damage is minimized and the surface forces are not limited by the light power. The magnitude of the deforming forces in the optical stretcher thus bridges the gap between optical tweezers and atomic force microscopy for the study of biologic materials.     

Restoration of Protein Synthesis after Death and the Effect of Postmortal Cooling

INVESTIGATIONS of the molecular mechanism of death in a complex organism have become possible with recent progress in cardiosurgery and the advent of mechanical substituents for the respiratory and circulatory systems which are switched off at death. Thus, using artificial circulation and radioactive tracers, we have studied protein synthesis in rabbits at various times after death and during “reanimation”. The rate of protein synthesis was evaluated according to the level of incorporation of free labelled amino-acids into the protein molecules.     

Neuroprosthetics of the upper extremity--clinical application in spinal cord injury and future perspectives.

Within the last couple of years, partial restoration of lost motor functions in a larger number of spinal cord injured patients has become possible by the introduction of neuroprostheses into the clinical environment. The Freehand system in particular is the first implantable neuroprosthesis from which a certain group of tetraplegic patients with stable shoulder function, but missing or weak grasp and hold function of the hand do benefit. The system is based on the combination of electrical stimulation and operative tendon transfers and thus represents a multicomponent concept for long-term restoration of the grasp function. The crucial prerequisites for successful use of an implantable neuroprosthesis are the right indication, careful preoperative muscle stimulation, differentiated planning of the surgery and functional training adopted to the individual residual functions. After successful completion of an extensive rehabilitation program, patients are able to use the system for activities of daily living without the need for special additional aids, which enhances their quality of life and independency. In order to extend the group of potential users of neuroprostheses in the future, new technological developments will have to take into account that nowadays the majority of spinal cord injured patients suffer from an incomplete lesion of the spinal cord. For these particular patients who still possess residual functions, modular, "naturally" controllable systems for supporting these functions are needed rather than complex systems to substitute them.