Synthetic and living micropropellers for convection-enhanced nanoparticle transport

Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable “living ferrofluid” by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.ISSN:2375-254

Designing Zero Energy Building for TehranB37B36:B44M35B36

In this paper, design of a zero energy building (ZEB), a case study for Tehran, in a moderately warm climate, for a typical single family has been introduced. It is important to develop solar energy resource potential in order to use it in construction of enhanced buildings. The benefits including reducing fossil fuel consumption, fading energy supply cost and lowering environmental pollutants, have created a growing tendency to these types of buildings. Calculating solar energy radiation and the house load are the basic steps to design a ZEB. Following steps are designing the heating, cooling and domestic hot water (DHW) systems and providing the electricity for appliances and lighting and designing the storage system. Economical features and environmental issues make ZEBs an appropriate solution for emerged problems of common houses and thus investments in large (state-wide) scales may be justified

Synthesis and in vitro dual calcium channel antagonist-agonist activity of some 1,4-Dihydo-2,6-dimethyl-3-nitro and cyano-4-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-pyridinecarboxylates

Background and purpose of the study: The vasorelaxant action of the dihydropyridines (DHPs) provides many useful clinical indications. However, their negative effects on cardiac contractility is still of a great concern especially in patients with heart failure. Design and synthesis of dual action compounds, i.e. smooth muscle calcium channel antagonist/cardiac muscle calcium channel agonist provides better and safer compounds particularly in patients with compromised cardiac contractility. In the present study, dual cardioselective Ca(2+) channel agonists / vascular selective smooth muscle Ca(2+) channel antagonists as third generation of DHP drugs were synthesized by a reported method. Methods: Synthetic procedure involved condensation of isopropyl-3-aminocrotonate with nitroacetone and 1-methyl-5-nitroimidazole2-carboxaldehyde and condensation of alkylacetoacetates with 3-aminocrotonitryl and 1-methyl-5-nitro-1H-imidazole-2carbaldehyde for the preparation of 1,4-Dihydo-2,6-dimethyl-3-nitro and cyano-4-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-pyridinecarboxylates, respectively. The in vitro effects of the synthesized compounds were evaluated on longitudal Smooth Muscle (GPILSM) and Guinea Pig Left Atrium (GPLA) preparations and finally, their conformations and structure-activity relationships were assessed. Results and major conclusion: All compounds showed calcium channel antagonist activity on isolated guinea pig ileum and some of them showed calcium channel agonist effects (or positive inotropic effect instead of calcium channel agonist effect) on isolated guinea-pig left atrium. QSAR and conformational analyses showed that conformation and charge of aryl substituents at C4 position have a main role in antagonistic activity while carbonyl group at C(5) position plays an important role in agonistic effects

Evaluation of Serum Levels of Zinc, Copper, Iron, and Zinc/Copper Ratio in Cutaneous Leishmaniasis

Background: The purpose of this study was to evaluate the levels of zinc (Zn), copper (Cu), iron (Fe) and zinc/ cop­per ratio in the serum of patients with cutaneous leishmaniasis in Qom Province, center of Iran. Methods: Serum levels of zinc and copper were determined by flame atomic absorption spectrophotometer and serum iron concentration was measured by using an Auto Analyzer. The study group consisted of 60 patients with cutaneous leishmaniasis and the control group of 100 healthy volunteers from the same area who were not exposed to cutane­ous leishmaniasis. Result: There were no statistically significant differences in age and body mass index between the two groups. Se­rum Zn (P< 0.001) and Fe (P< 0.05) levels were lower in patients with cutaneous leishmaniasis than the control group. We also found serum Cu concentration (P< 0.05) in the patient group was significantly higher than that of the control group. However, zinc/ copper ratio (P< 0.001) was lower in patients with cutaneous leishmaniasis than in the control group. Conclusion: Our data indicated that Zn/Cu ratio was significantly lower in patients with CL as compared to the con­trols. Earlier reports suggest that, this ratio imbalance could be a useful marker for immune dysfunction in leishma­niasis. There was also strong association of Zn, Cu and Fe with CL. It suggests the use of blood zinc, copper, iron concentration and the copper/zinc ratio (Zn/Cu), as a means for estimating the prognosis of CL

A Pulsatile Flow System to Engineer Aneurysm and Atherosclerosis Mimetic Extracellular Matrix

Alterations of blood flow patterns strongly correlate with arterial wall diseases such as atherosclerosis and aneurysm. Here, a simple, pumpless, close-loop, easy-to-replicate, and miniaturized flow device is introduced to concurrently expose 3D engineered vascular smooth muscle tissues to high-velocity pulsatile flow versus low-velocity disturbed flow conditions. Two flow regimes are distinguished, one that promotes elastin and impairs collagen I assembly, while the other impairs elastin and promotes collagen assembly. This latter extracellular matrix (ECM) composition shares characteristics with aneurysmal or atherosclerotic tissue phenotypes, thus recapitulating crucial hallmarks of flow-induced tissue morphogenesis in vessel walls. It is shown that the mRNA levels of ECM of collagens and elastin are not affected by the differential flow conditions. Instead, the differential gene expression of matrix metalloproteinase (MMP) and their inhibitors (TIMPs) is flow-dependent, and thus drives the alterations in ECM composition. In further support, treatment with doxycycline, an MMP inhibitor and a clinically used drug to treat vascular diseases, halts the effect of low-velocity flow on the ECM remodeling. This illustrates how the platform can be exploited for drug efficacy studies by providing crucial mechanistic insights into how different therapeutic interventions may affect tissue growth and ECM assembly

Synthetic and living micropropellers for convection-enhanced nanoparticle transport

Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum(ABF), and in the second approach,we used swarms of magnetotactic bacteria (MTB) to create a directable "living ferrofluid" by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidicmodel of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.National Cancer Institute (Grant P30-CA1405