The validation of a generalized Hooke's law for coronary arteries

The exponential form of constitutive model is widely used in biomechanical studies of blood vessels. There are two main issues, however, with this model: 1) the curve fits of experimental data are not always satisfactory, and 2) the material parameters may be oversensitive. A new type of strain measure in a generalized Hooke's law for blood vessels was recently proposed by our group to address these issues. The new model has one nonlinear parameter and six linear parameters. In this study, the stress-strain equation is validated by fitting the model to experimental data of porcine coronary arteries. Material constants of left anterior descending artery and right coronary artery for the Hooke's law were computed with a separable nonlinear least-squares method with an excellent goodness of fit. A parameter sensitivity analysis shows that the stability of material constants is improved compared with the exponential model and a biphasic model. A boundary value problem was solved to demonstrate that the model prediction can match the measured arterial deformation under experimental loading conditions. The validated constitutive relation will serve as a basis for the solution of various boundary value problems of cardiovascular biomechanics.     

Novel bimodal bifunctional ligands for radioimmunotherapy and targeted MRI

The structurally novel bifunctional ligands C-NETA and C-NE3TA, each possessing both acyclic and macrocyclic moieties, were prepared and evaluated as potential chelates for radioimmunotherapy (RIT) and targeted magnetic resonance imaging (MRI). Heptadentate C-NE3TA was fortuitously discovered during the preparation of C-NETA. An optimized synthetic method to C-NETA and C-NE3TA including purification of the polar and tailing reaction intermediates, tert-butyl C-NETA (2) and tert-butyl C-NE3TA (3) using semiprep HPLC was developed. The new Gd(III) complexes of C-NETA and C-NE3TA were prepared as contrast enhancement agents for use in targeted MRI. The T 1 relaxivity data indicate that Gd(C-NETA) and Gd(C-NE3TA) possess higher relaxivity than Gd(C-DOTA), a bifunctional version of a commercially available MRI contrast agent; Gd(DOTA). C-NETA and C-NE3TA were radiolabeled with (177)Lu, (90)Y, (203)Pb, (205/6)Bi, and (153)Gd; and in vitro stability of the radiolabeled corresponding complexes was assessed in human serum. The in vitro studies indicate that the evaluated radiolabeled complexes were stable in serum for 11 days with the exception being the (203)Pb complexes of C-NETA and C-NE3TA, which dissociated in serum. C-NETA and C-NE3TA radiolabeled (177)Lu, (90)Y, or (153)Gd complexes were further evaluated for in vivo stability in athymic mice and possess excellent or acceptable in vivo biodistribution profile. (205/6)Bi- C-NE3TA exhibited extremely rapid blood clearance and low radioactivity level at the normal organs, while (205/6)Bi- C-NETA displayed low radioactivity level in the blood and all of the organs except for the kidney where relatively high renal uptake of radioactivity is observed. C-NETA and C-NE3TA were further modified for conjugation to the monoclonal antibody Trastuzumab.     

Efficient synthesis and evaluation of bimodal ligand NETA

The efficient and short synthetic route to the structurally novel bimodal ligand NETA for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer was developed. The structure of NETA was determined by X-ray crystallography. The arsenazo-based UV spectroscopic complexation kinetics data suggest that NETA is a promising chelator for use in RIT applications of (212)Bi, (213)Bi, and (177)Lu.     

Distribution and symptoms of epiphyte infection in major carrageenophyte-producing farms

High density commercial farming of carrageenophyte Kappaphycus alvarezii is often plagued with “ice-ice” disease and epiphyte infection, which eventually leads to reduced production and in some cases collapse of crop. Epiphyte outbreak has been occurring regularly in major carrageenophyte farms in the Philippines, Indonesia, Malaysia and Tanzania. Infected materials from these countries were studied to establish baseline information on the epiphyte’s identity, density, symptoms and secondary infection on the host seaweed. The causative organism was identified as Neosiphonia apiculata (Hollenberg) Masuda et Kogame, based on its morphological features. Epiphyte density on host seaweed materials decreased in the following order: the Philippines (88.5 epi cm⁻²), Tanzania (69.0 epi cm⁻²), Indonesia (56.5 epi cm⁻²) and Malaysia (42.0 epi cm⁻²). Initial symptoms were the presence of tiny black spots, indicating the embedded tetrasporeling in seaweed cortex layer. Vegetative form emerged after 2 weeks measuring less than 0.5 mm in length with a density of less than 25.0 epi cm⁻². Upon maturation, infected seaweed takes on a “hairy” appearance with “goose-bumps” like cortical swellings. The epiphyte appears as a solitary plant with multiple secondary rhizoids or as multiple epiphytes appearing from a single cortical opening. At the end of infection, the epiphytes left dark pits on the cortical swelling, and the carrageenophytes are infected by opportunistic bacteria. Bacterial enumeration of healthy and infected seaweed materials showed an increase of more than 300% in total bacterial count on infected materials dominated by Alteromonas sp., Flavobacterium sp. and Vibrio sp.     

Effects of ligands or substrate of insulin-regulated aminopeptidase (IRAP) on trophoblast invasion.

Insulin-regulated aminopeptidase (IRAP) activity increases during placentation and in the invasive tumor cell of trophoblast suggesting a role for this peptidase in the invasiveness of normal and malignant trophoblast. To investigate this hypothesis, we studied the effects of substrate (OT) and inhibitors (angiotensin peptides and LVV-H7) of IRAP on the first trimester trophoblast proliferation and invasion. Addition of these peptides in the culture medium of trophoblastic cells significantly decreased metalloproteinase-9 activity and cellular invasiveness while no effect was observed on cell proliferation. The peptide IRAP inhibitors could exert their effect on cytotrophoblastic cell invasiveness by inhibition of its enzymatic activity, and thus increasing half life of the known placental peptide substrate of IRAP, OT.     

Decreased interaction between ZO-1 and occludin is involved in alteration of tight junctions in transplanted epiphora submandibular glands

Tight junctions (TJs) in salivary epithelium play an important role in regulating saliva secretion. Autologous transplantation of submandibular glands (SMGs) is an effective method to treat severe dry eye syndrome. However, epiphora occurs in some patients 6 months after transplantation. We previously found that the acinar TJs are enlarged in rabbit SMGs after long-term transplantation, but the exact TJ components involved in the epiphora are still unknown. Here, we found that the mRNA and protein expression of ZO-1 and occludin were increased in the transplanted SMGs obtained from epiphora patients, while other TJs were unchanged. The intensity of ZO-1 and occludin at the apicolateral membranes as well as occludin in the cytoplasm were increased in epiphora SMGs, but the interaction between ZO-1 and occludin was decreased as evidenced by both co-immunoprecipitation assay and co-immunofluorescence staining. Mechanically, the expression of casein kinase 2α (CK2α) and CK2β, which was reported to affect occludin modification and the interaction of occludin with ZO-1 in previous literatures, were increased in epiphora glands. Moreover, activation of muscarinic acetylcholine receptor (mAChR) by carbachol directly decreased the interaction between ZO-1 and occludin and increased the acinar TJ width in the freshly isolated human SMGs, whereas these effects were abolished by pretreatment with CK2 inhibitor. Taken together, our findings suggest that decreased interaction between ZO-1 and occludin might contribute to the epiphora occurred in the transplanted SMGs, and mAChR together with the intracellular molecule CK2 might be responsible for the alteration of TJs in epiphora glands.     

The acute effects of dynamic and ballistic stretching on vertical jump height, force, and power

Stretching before performance is a common practice among athletes in hopes of increasing performance and reducing the risk of injury. However, cumulative results indicate a negative impact of static stretching and proprioceptive neuromuscular facilitation (PNF) on performance; thus, there is a need for evaluating other stretching strategies for effective warm-up. The purpose of this study was to compare the differences between two sets of ballistic stretching and two sets of a dynamic stretching routine on vertical jump performance. Twenty healthy male and female college students between the ages of 22 and 34 (24.8 +/- 3 years) volunteered to participate in this study. All subjects completed three individual testing sessions on three nonconsecutive days. On each day, the subjects completed one of three treatments (no stretch, ballistic stretch, and dynamic stretch). Intraclass reliability was determined using the data obtained from each subject. A paired samples t-test revealed no significant difference in jump height, force, or power when comparing no stretch with ballistic stretch. A significant difference was found on jump power when comparing no stretch with dynamic stretch, but no significant difference was found for jump height or force. Statistics showed a very high reliability when measuring jump height, force, and power using the Kistler Quattro Jump force plate. It seems that neither dynamic stretching nor ballistic stretching will result in an increase in vertical jump height or force. However, dynamic stretching elicited gains in jump power poststretch.