This review is an account of recent advances in our understanding of the mechanisms of thrombus formation, with emphasis on two independent pathways: one involving primarily platelets and the other initiated by tissue factor.

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Mechanisms of Thrombus Formation

Hypoplastic Left Heart Syndrome : Current Considerations and Expectations

Nanotechnology offers the food industry a number of new approaches for improving the quality, shelf life, safety, and healthiness of foods. Nevertheless, there is concern from consumers, regulatory agencies, and the food industry about potential adverse effects (toxicity) associated with the application of nanotechnology in foods. In particular, there is concern about the direct incorporation of engineered nanoparticles into foods, such as those used as delivery systems for colors, flavors, preservatives, nutrients, and nutraceuticals, or those used to modify the optical, rheological, or flow properties of foods or food packaging. This review article summarizes the application of both inorganic (silver, iron oxide, titanium dioxide, silicon dioxide, and zinc oxide) and organic (lipid, protein, and carbohydrate) nanoparticles in foods, highlights the most important nanoparticle characteristics that influence their behavior, discusses the importance of food matrix and gastrointestinal tract effects on nanoparticle properties, emphasizes potential toxicity mechanisms of different food-grade nanoparticles, and stresses important areas where research is still needed. The authors note that nanoparticles are already present in many natural and processed foods, and that new kinds of nanoparticles may be utilized as functional ingredients by the food industry in the future. Many of these nanoparticles are unlikely to have adverse affects on human health, but there is evidence that some of them could have harmful effects and that future studies are required.

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Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles

The development of different kinds of nanoparticles, showing different physico-chemical properties, has fostered their large use in many fields, including medicine. As a consequence, inorganic nanoparticles (e.g., metals or semiconductors), have raised issues about their potential toxicity. The scientific community is investigating the toxicity mechanisms of these materials, in vitro and in vivo, in order to provide accurate references concerning their use. This review will give the readers a thorough exploration on the entry mechanisms of inorganic nanoparticles in the human body, such as titanium dioxide nanoparticles (TiO2NPs), silicon dioxide nanoparticles (SiO2NPs), zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and quantum dots (QDsNPs). In addition, biodistribution, the current trends and novelties of in vitro and in vivo toxicology studies will be discussed, with a particular focus on immune response.

Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response, Biodistribution and In Vitro/In Vivo Toxicity Evaluation.

The development of new nanomaterials with high biomedical performance and low toxicity is essential to obtain more efficient therapy and precise diagnostic tools and devices. Recently, scientists often face issues of balancing between positive therapeutic effects of metal oxide nanoparticles and their toxic side effects. In this review, considering metal oxide nanoparticles as important technological and biomedical materials, the authors provide a comprehensive review of researches on metal oxide nanoparticles, their nanoscale physicochemical properties, defining specific applications in the various fields of nanomedicine. Authors discuss the recent development of metal oxide nanoparticles that were employed as biomedical materials in tissue therapy, immunotherapy, diagnosis, dentistry, regenerative medicine, wound healing and biosensing platforms. Besides, their antimicrobial, antifungal, antiviral properties along with biotoxicology were debated in detail. The significant breakthroughs in the field of nanobiomedicine have emerged in areas and numbers predicting tremendous application potential and enormous market value for metal oxide nanoparticles.

https://www.mdpi.com/2313-7673/5/2/27/pdf

Metal Oxide Nanoparticles as Biomedical Materials

Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitot...

Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

https://www.internationaljournalofcardiology.com/article/S0167-5273(06)01347-7/pdf

Impaired vascular function in patients with Fontan circulation.

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1+/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.

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Endothelial Dysfunction and Microvascular Complications in Type 1 Diabetes Mellitus

The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two-dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9±4.6° vs. 0.3±2.1°, p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9±4.1° vs. -0.9±3.1°, p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM.

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Decreased left ventricular torsion and untwisting in children with dilated cardiomyopathy.

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

Seon Mi Jin

Papers

Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

Impaired vascular function in patients with Fontan circulation.

Endothelial Dysfunction and Microvascular Complications in Type 1 Diabetes Mellitus

Decreased left ventricular torsion and untwisting in children with dilated cardiomyopathy.

Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.