[A 3D-ultrasound imaging system based on back-end scanning mode].

A new scanning mode is proposed that the front-end of the probe is fixed, while the back-end makes fan-shaped, scanning movement. The new scanning mode avoided ribs drawbacks successfully. Based on the new scanning mode a 3D-Ultrasound Images System is accomplished to acquire 2D data of fetusfetus fetusfetus phantom and livers and kidneys, to demonstrates the effectiveness of the new scanning mode.

Fluorescence studies on a designed self-assembling peptide of RAD16-II as a potential carrier for hydrophobic drug.

The self-assembling peptide, RAD16-II (Ac-RARADADARARADADA-NH2), has been shown to have many great applications in nanotechnology and tissue engineering. But few studies have been carried out to study the application of self-assembling peptides as a drug carrier. We used hydrophobic drug pyrene as a model and liposome vesicles to mimic bilayer membranes to study the ability of RAD16-II in drug encapsulation and transfer to lipid vesicles. It was found that this designed self-assembling peptide was able to stabilize hydrophobic drug in aqueous solution and deliver it into lipophilic environment. Analysis of the fluorescence excitation spectra showed that pyrene was present in the crystalline form when stabilized by RAD16-II and was able to be dispersed in egg phosphatidylcholine vesicles. This suggested that pyrene was completely released from RAD-Py mixture into the bilayer membranes. Furthermore, the concentration of pyrene transferred into the vesicles was quantified and its transfer rate was determined. The scanning electron micrograph image showed that pyrene microcrystals and peptide were absorbed by each other and the size of the pyrene-peptide complexes was larger than 10 microm. These data further demonstrated that this type of ionic complementary oligopeptides was able to significantly encapsulate hydrophobic drug and provide a new type of nanomaterials for delivering drugs.

Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha.

AIMS: We investigated whether hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a role in the acute phase of ischaemic preconditioning (IPC). METHODS AND RESULTS: Hearts from wild-type (WT) mice and mice heterozygous for a null allele at the locus encoding HIF-1 alpha (HET) were subjected to IPC (10-min ischaemia/5 min reperfusion, or two cycles of 5 min ischaemia/5 min reperfusion), followed by 30 min ischaemia and reperfusion. Left ventricular-developed pressure, heart rate, and coronary flow rate were measured continuously. Apoptosis and infarct size were assessed by TUNEL assay, cleaved caspase 3 immunohistochemistry, and triphenyltetrazolium chloride staining. Production of reactive oxygen species (ROS) in isolated cardiac mitochondria was measured by a chemiluminescence assay. The phosphatase and tensin homologue (PTEN) and AKT (protein kinase B) were analysed by immunoblot assay. IPC improved functional recovery and limited infarct size and apoptosis after prolonged ischaemia-reperfusion in WT hearts, but not in HET hearts. Mitochondrial ROS production, PTEN oxidation, and AKT phosphorylation were impaired in HET hearts. WT and HET hearts were protected by adenosine, which acts via an ROS-independent mechanism. CONCLUSION: HIF-1 alpha is required for IPC-induced mitochondrial ROS production and myocardial protection against ischaemia-reperfusion injury.

Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity.

Disruption of leptin signaling is associated with obesity, heart failure, and cardiac hypertrophy, but the role of leptin in cardiac myocyte apoptosis is unknown. We tested the hypothesis that apoptosis increases in leptin-deficient ob/ob and leptin-resistant db/db mice and is associated with aging and left ventricular hypertrophy, increased DNA damage, and decreased survival. We studied young (2- to 3-month-old) and old (12- to 14-month-old) ob/ob and db/db mice and wild-type (WT) controls (n=2 to 4 per group). As expected, ventricular wall thickness and heart weights were similar among young ob/ob, db/db, and WT mice, but higher in old ob/ob and db/db versus old WT. Young ob/ob and db/db showed markedly elevated apoptosis by TUNEL staining and caspase 3 levels compared with WT. Differences in apoptosis were further accentuated with age. Leptin treatment significantly reduced apoptosis in ob/ob mice both in intact hearts and isolated myocytes. Tissue triglycerides were increased in ob/ob hearts, returning to WT levels after leptin repletion. Furthermore, the DNA damage marker, 8oxoG (8-oxo-7,8-dihydroguanidine), was increased, whereas the DNA repair marker, MYH glycosylase, was decreased in old ob/ob and db/db compared with old WT mice. Both ob/ob and db/db mice had decreased survival compared with WT mice. We conclude that leptin-deficient and leptin-resistant mice demonstrate increased apoptosis, DNA damage, and mortality compared with WT mice, suggesting that normal leptin signaling is necessary to prevent excess age-associated DNA damage and premature mortality. These data offer novel insights into potential mechanisms of myocardial dysfunction and early mortality in obesity.

Recent advances in basic and clinical nanomedicine.

Nanomedicine is a global business enterprise. Industry and governments clearly are beginning to envision nanomedicine's enormous potential. A clear definition of nanotechnology is an issue that requires urgent attention. This problem exists because nanotechnology represents a cluster of technologies, each of which may have different characteristics and applications. Although numerous novel nanomedicine-related applications are under development or nearing commercialization, the process of converting basic research in nanomedicine into commercially viable products will be long and difficult. Although realization of the full potential of nanomedicine may be years or decades away, recent advances in nanotechnology-related drug delivery, diagnosis, and drug development are beginning to change the landscape of medicine. Site-specific targeted drug delivery and personalized medicine are just a few concepts that are on the horizon.

New technology and clinical applications of nanomedicine.

Nanomedicine is the use of nanotechnology to achieve innovative medical breakthroughs. Nanomedicine, with its broad range of ideas, hypotheses, concepts, and undeveloped clinical devices, is still in its early stage. This article outlines present developments and future prospects for the use of nanotechnology techniques in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use n diagnosis and therapy in the fields of genetics, oncology, cardiology, and dermatology. Toxicologic considerations also are discussed.

Nanomedicine and drug delivery.

This article discusses the use of nanotechnology in drug delivery approaches. Magnetic nanotechnology is finding wide applications in medicine, most notably in MRI and magnetic separation. The impedance biosensor is expected to find applications in monitoring cytokines in cancer, bone turnover markers in osteoporosis, and understanding neural-degenerative diseases.

New advances in nanomedicine: diagnosis and preventive medicine.

This article describes the use of nanobiologic techniques in diagnosis and preventive medicine. It discusses the engineering of fluorescent and bioluminescent proteins to visualize biologic functions; single-molecule measurements of protein structure and function; two-photon microscopy for molecular imaging of the structure and function in living cells and tissues; and imaging ligand-induced protein conformations and interactions by fluorescence in single living cells.

Genetic nanomedicine and tissue engineering.

This article describes current investigative directions in nanotechnology-based medicine. It discusses cell sheet engineering, the molecular design of self-assembling peptide nanomaterials; the reconstitution of membrane protein systems on giant liposomes as artificial cell models, a biochemically engineered molecular communication system, and the use of split-reporter reconstitution analysis to image biomolecules in living cells and animals.

From bench to bedside: successful translational nanomedicine: highlights of the Third Annual Meeting of the American Academy of Nanomedicine.

The Third Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the University of California San Diego, in San Diego, California during September 7-8, 2007. The meeting was focused on successful translational nanomedicine: from bench to bedside. There were four keynote lectures and eight scientific symposiums in this meeting. The researchers and investigators reported the results and process of current nanomedicine research and approaches to clinical applications. The meeting provided exciting information for nanomedicine clinical-related researches and strategy for further development of nanomedicine research which will be benefits to clinical practice.

Epigallocathechin-3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and -independent signal pathways.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Recent in vitro and in vivo studies have suggested that reactive oxygen species (ROS) may play an important role in cardiac hypertrophy. It was therefore thought to be of particular value to examine the effects of antioxidants on cardiac hypertrophy. Epigallocatechin-3-gallate (EGCG) is a major bioactive polyphenol present in green tea and a potent antioxidant. The current study was designed to test the hypothesis that EGCG inhibits cardiac hypertrophy in vitro and in vivo. In this study, we investigated the effects of EGCG on angiotensin II- (Ang II) and pressure-overload-induced cardiac hypertrophy. Our results showed that EGCG attenuated Ang II- and pressure-overload-mediated cardiac hypertrophy. Both reactive oxygen species generation and NADPH oxidase expressions induced by Ang II and pressure overload were suppressed by EGCG. The increased hypertension by pressure overload was almost completely blocked after EGCG treatment. Further studies showed that EGCG inhibited Ang II-induced NF-kappaB and AP-1 activation. Inhibition of the activity of NF-kappaB was through blocking ROS-dependent p38 and JNK signaling pathways, whereas inhibition of AP-1 activation was via blocking EGFR transactivation and its downstream events ERKs/PI3K/Akt/mTOR/p70(S6K). The combination of these actions resulted in repressing the reactivation of ANP and BNP, and ultimately preventing the progress of cardiac hypertrophy. These findings indicated that EGCG prevents the development of cardiac hypertrophy through ROS-dependent and -independent mechanisms involving inhibition of different intracellular signaling transductional pathways.

Increased mitochondrial reactive oxygen species production in newborn brain during hypoglycemia.

Hypoglycemia is associated with gray and white matter injury in immature brain, but the specific mechanisms responsible for hypoglycemic brain injury remain poorly defined. We postulated that mitochondrial electron transport chain function is altered during hypoglycemia due to the decreased availability of reducing equivalents, and that altered activity of the electron transport chain would increase mitochondrial production of free radicals and lead to mitochondrial oxidant injury. The present study tests the hypothesis that production of reactive oxygen species (ROS) by cerebral mitochondria is increased during acute hypoglycemia. Studies were performed in an awake, chronically catheterized newborn piglet model. Hypoglycemia (blood glucose 1 mmol/L for 2 h) was induced using a bolus of intravenous lispro insulin, 25 U/kg. Superoxide and hydrogen peroxide production by mitochondria isolated from cerebral cortex of normoglycemic and hypoglycemic newborn piglets was measured using lucigenin- and luminol-derived chemiluminescence. After 2 h of hypoglycemia, superoxide generation was 60% higher and hydrogen peroxide generation was two-fold higher in mitochondria from hypoglycemia animals than in controls (p < 0.005). These data confirm that the ability of the mitochondria to produce ROS is increased after hypoglycemia in immature brain, and are, to our knowledge, the first evidence that ROS may play a role in brain injury due to neonatal hypoglycemia. Increased mitochondrial ROS production could result in alterations in brain structure and function due to oxidant injury to mitochondrial proteins and DNA or changes in oxidant-sensitive signal transduction pathways in brain.

Self-assembly peptide prevents blood loss.

Recently, researchers from the Massachusetts Institute of Technology and the University of Hong Kong discovered a new peptide that immediately stopped bleeding at the surgical site. Nanohemostat solution stops blood flow in less than 10 seconds in the cutting site of brain, spinal cord, femoral artery, and liver. Although the actual mechanism of action is not known, it is believed that the peptides are able to self-assemble into a nanofibrous scaffold network that provides these remarkable properties.

New technology and clinical applications of nanomedicine: highlights of the second annual meeting of the American Academy of Nanomedicine (Part I).

The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Academy of Science Building in Washington, DC, September 9-10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.

Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring.

Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring's aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention.

Isorhapontigenin, a new resveratrol analog, attenuates cardiac hypertrophy via blocking signaling transduction pathways.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. The hypertrophic process is mediated, in part, by oxidative stress-mediated signaling pathways. We hypothesized that isorhapontigenin (ISO), a new resveratrol analog, inhibits cardiac hypertrophy by blocking oxidative stress and oxidative stress-mediated signaling pathways. We treated cardiomyocytes with angiotensin II (Ang II) with or without ISO and found that ISO inhibited Ang II-induced cardiac hypertrophy. These effects were associated with a decrease in the levels of reactive oxygen species and H2O2 and the content of intracellular malonaldehyde and an increase in the activities of superoxide dismutase and glutathione peroxidase. Ang II induced the phosphorylation of PKC, Erk1/2, JNK, and p38 in cardiomyocytes and such phosphorylation was inhibited by ISO. ISO also blocked the PKC-dependent PI3K-Akt-GSK3beta/p70S6K pathway. These effects lead to direct or indirect inhibition of NF-kappaB and AP-1 activation. Our results revealed that pretreatment with ISO significantly inhibited Ang II-mediated NF-kappaB through affecting the degradation and phosphorylation of IkappaBalpha and the activity of IKKbeta and AP-1 activation by influencing the expression of c-Fos and c-Jun proteins. In addition, we also established the molecular link between activation of PKC and MAPKs and activation of NF-kappaB and AP-1 in cardiomyocytes. We also found that ISO treatment significantly attenuated heart weight/body weight ratio by approximately 25%, decreased posterior wall thickness and left ventricle diastolic and systolic diameters, and increased 10% fractional shortening in an aortic-banded rat model. Furthermore, treatment with ISO significantly decreased cardiac myocyte size and systolic blood pressure. These findings suggest that ISO prevents the development of cardiac hypertrophy through an antioxidant mechanism involving inhibition of different intracellular signaling transduction pathways.

The pathway to commercialization for nanomedicine.

Nanomedicine is a global opportunity that will change the face of medicine and drug delivery in the next 20 years. To date, US firms have focused primarily on the science and less on the commercial application of nanomedicine. As a result, there remain significant obstacles in bringing a nanomedicine product to market. Overcoming those obstacles will require a multidisciplinary approach to commercialization. This article will look at the emerging nanomedicine market, the current view from the investment community, and some of the obstacles facing the commercialization of nanomedicine science.

Modeling and characterization of a nanoliter drug-delivery MEMS micropump with circular bossed membrane.

A MEMS (micro-electro-mechanical systems) micropump with circular bossed membrane designed for nanoliter drug delivery is characterized in this article. A quasistatic model under consideration of low operating frequency is used to characterize this micropump. The mathematical model is an ordinary differential equation that describes the behavior of the micropump by including its key components of bossed membrane and inlet/outlet microvalves. Characterizations of bossed membrane and microvalves are carried out separately in the finite element analysis ANSYS package. The stroke volume of the membrane is calculated within the range that the linear deflection theory is valid. Analysis of the microvalve is a challenging task in microfluidics because it is a coupled field (solid-fluid coupling) problem. To solve the structural (solid) or fluid part separately is impractical in characterizing drug-delivery micropumps. Based on sequential weak solid-fluid coupling in ANSYS/FLOTRAN, the flow rates across the inlet and outlet microvalves are analyzed and simulated. Because the quasistatic equation contains several nonlinear terms, closed-form analytical solution for this equation is impossible; thus MATLAB is used to solve it numerically. The transient flow rate of the micropump is obtained by substituting the pressure in microchamber into the flow rate function of outlet microvalves. Integration of the function over 1 driving cycle and multiplication by the driving frequency provides the drug-delivery rate of the micropump.

Protecting new ideas and inventions in nanomedicine with patents.

New paradigms are shrinking our world. Tiny is in and patents are essential for success in nanomedicine. In fact, patents are already shaping this nascent and rapidly evolving field. For the past decade a swarm of patent applications pertaining to nanomedicine has been arriving at the US Patent and Trademark Office (PTO). As companies develop products and processes and begin to seek commercial applications for their inventions, securing valid and defensible patent protection will be vital to their long-term survival. As we enter the "golden era" of medicine, or nanomedicine, in the next decade with the field maturing and the promised breakthroughs accruing, patents will generate licensing revenue, provide leverage in deals and mergers, and reduce the likelihood of infringement. Because development of nanobiotechnology- and nanomedicine-related products is extremely research intensive, without the market exclusivity offered by a US patent, development of these products and their commercial viability in the marketplace will be significantly hampered. In this article, we highlight critical issues relating to patenting nanomedicine products. Effects of the "nanopatent land grab" that is underway in nanomedicine by "patent prospectors" are examined as startups and corporations compete to lock up broad patents in these critical early days. Because nanomedicine is multidisciplinary, patenting presents unique opportunities and poses numerous challenges. Although patents are being sought more actively and enforced more vigorously, the entire patent system is under greater scrutiny and strain, with the PTO continuing to struggle with evaluating nanomedicine-related patent applications.