Thermo-, photo-, and mechano-responsive liquid crystal networks enable tunable photonic crystals.

Tunable photonic crystals exhibiting optical properties that respond reversibly to external stimuli have been developed using liquid crystal networks (LCNs) and liquid crystal elastomers (LCEs). These tunable photonic crystals possess an inverse opal structure and are photo-responsive, but circumvent the usual requirement to contain dye molecules in the structure that often limit their applicability and cause optical degradation. Herein, we report tunable photonic crystal films that reversibly tune the reflection peak wavelength under thermo-, photo- and mechano-stimuli, through bilayering a stimuli-responsive LCN including azobenzene units with a colourless inverse opal film composed of non-responsive, flexible durable polymers. By mechanically deforming the azobenzene containing LCN via various stimuli, the reflection peak wavelength from the bilayered film assembly could be shifted on demand. We confirm that the reflection peak shift occurs due to the deformation of the stimuli-responsive layer propagating towards and into the inverse opal layer to change its shape in response, and this shift behaviour is repeatable without optical degradation.

Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection.

Keratoplasty is the primary treatment to cure blindness due to corneal opacification. However, immune-mediated rejection remains the leading cause of keratoplasty failure. Here, we utilize an in vivo imaging approach to monitor, track, and characterize in real-time the recruitment of GFP-labeled allo-specific activated (Bonzo) T cells during corneal allograft rejection. We show that the recruitment of effector T cells to the site of transplantation determined the fate of corneal allografts, and that local intra-graft production of CCL5 and CXCL9/10 regulated motility patterns of effector T cells in situ, and correlated with allograft rejection. We also show that different motility patterns associate with distinct in vivo phenotypes (round, elongated, and ruffled) of graft-infiltrating effector T cells with varying proportions during progression of rejection. The ruffled phenotype was characteristic of activated effectors T cells and predominated during ongoing rejection, which associated with significantly increased T cell dynamics within the allografts. Importantly, CCR5/CXCR3 blockade decreased the motility, size, and number of infiltrating T cells and significantly prolonged allograft survival. Our findings indicate that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells, and may guide targeted interventions to promote graft survival.

Clinical intraocular islet transplantation is not a number issue.

It is now well established that beta cell replacement through pancreatic islet transplantation results in significant improvement in the quality-of-life of type 1 diabetes (T1D) patients. This is achieved through improved control and prevention of severe drops in blood sugar levels. Islet transplant therapy is on the verge of becoming standard-of-care in the USA. Yet, as with other established transplantation therapies, there remain hurdles to overcome to bring islet transplantation to full fruition as a long-lasting therapy of T1D. One of these hurdles is establishing reliable new sites, other than the liver, where durable efficacy and survival of transplanted islets can be achieved. In this article, we discuss the anterior chamber of the eye as a new site for clinical islet transplantation in the treatment of T1D. We specifically focus on the common conceptions, and preconceptions, on the requirements of islet mass, and whether or not the anterior chamber can accommodate sufficient islets to achieve meaningful efficacy and significant impact on hyperglycemia in clinical application.

Pharmacokinetics of nilvadipine in healthy volunteers.

The pharmacokinetics of nilvadipine, a new antihypertensive and antianginal drug, were examined in healthy male volunteers. In a Latin square, three-way crossover design with a one-day run-in period, six subjects in three groups of two each were given single 2-, 4-, or 6-mg oral doses of nilvadipine after overnight fasting. Nilvadipine plasma concentrations up to 32 hours after drug treatment were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry (detection limit, 0.01 ng/mL). Nilvadipine urinary concentrations were determined by capillary column gas chromatography with electron capture detector (detection limit, 0.5 ng/mL). Nilvadipine plasma concentrations declined in a bi- or triexponential pattern after reaching the maximum plasma concentrations. The mean +/- standard deviation maximum plasma concentrations of 1.48 +/- 0.47, 3.48 +/- 0.53, and 6.69 +/- 1.54 ng/mL were attained from 1.08 to 1.50 hours after doses of 2, 4, and 6 mg, respectively. The elimination half-life was dose-independent and averaged 11.0 +/- 2.3 hours. The area under the plasma concentration-time curve increased in proportion to the dose. Nilvadipine was not detected in the urine. The pharmacokinetics of nilvadipine were generally linear over the dosage range studied. Besides the above model-independent pharmacokinetic parameters, model-dependent parameters were also obtained by curve-fitting the plasma data to a bi- or triexponential equation with zero-order absorption. Nilvadipine decreased blood pressure slightly and in a dose-dependent fashion.

Effect of two different meals on bioavailability of nilvadipine in healthy volunteers.

The effect of two different meals on the bioavailability of nilvadipine, a new antihypertensive and antianginal drug, was examined in 16 healthy male volunteers in two separate studies. In each study of eight subjects in a Latin-square, two-way crossover design, two groups of four subjects each were given a single 6-mg oral dose of nilvadipine after overnight fasting or 30 minutes after a 464- or 748-kcal meal. There were no significant differences in the area under the plasma concentration-time curve or the maximum plasma concentration between the fasting and fed states for either meal. Although the time to reach the maximum plasma concentration was about the same after a 464-kcal meal and after fasting, it increased slightly but significantly after a 748-kcal meal, indicating possible delay in drug absorption after meals. These studies showed that the extent of bioavailability of nilvadipine appears to be little affected in the presence of food. Although a possible delay in the onset of absorption would occur, such a delay may not have any therapeutic importance in chronic therapy.

Multiple-dose pharmacokinetics of nilvadipine in healthy volunteers.

Nilvadipine, a new antihypertensive and antianginal drug, was studied in six healthy male volunteers to evaluate its steady-state pharmacokinetics after oral dosing. The subjects were given a single dose of 4 mg, followed by 4 mg every 12 hours for six days after a washout period of more than 3 days. The pharmacokinetics of nilvadipine were well described by a linear model of triexponential equation with zero-order absorption. The steady state was reached by the fourth day of multiple dosing, with a twofold accumulation of trough plasma concentration and no accumulation of peak concentration. The mean plasma concentration at steady state was 1.0 ng/mL. The optical enantiomers of nilvadipine were also determined in the plasma. The plasma concentration of (+)-nilvadipine was about two and a half times higher than that of (-)-nilvadipine, and this ratio was unaffected by multiple dosing.

Cyclolinopeptides F-I, cyclic peptides from linseed.

Four cyclic peptides, cyclolinopeptides F-I, were isolated from seeds of Linum usitatissimum. Their structures were elucidated by extensive 2D NMR spectroscopic methods and by chemical degradation. Further, their immunosuppressive activity is examined.

Semi-micro plaque neutralization test for rubella antibody.

Attenuated rubella virus, strain Cendehill, was found to produce small, distinct and ring-shaped plaques in Vero cell cultures. This finding was utilized to develop a semi-micro plaque neutralization test for a rubella antibody in 14 cmX9cm (24 wells) plastic trays. The procedure represents a reproducible and economical way to measure rubella neutralizing antibody.

All-optical image processing by means of a photosensitive nonlinear liquid-crystal film: edge enhancement and image addition-subtraction.

We demonstrate two simple yet efficient all-optical image-processing techniques that use nonlinear photosensitive dye-doped nematic liquid-crystal films, namely, edge enhancement and image addition-subtraction operations. These films require no external bias and function at much lower optical powers and shorter response times than other conventional methods.

Antibody responses in the cerebrospinal fulid of cynomolgus monkeys after intracerebral inoculation with paramyxoviruses.

Cynomolgus monkeys with or without measles antibody were intracerebrally inoculated with measles or canine distemper viruses, and antibody responses in the cerebrospinal fluid (CSF) were investigated. In measles antibody-free monkeys, natural infection with wild measles virus or intracerebral inoculations with two attenuated measles vaccines evoked primary antibody responses to measles virus in the sera but not in the CSF. In measles-immune monkeys, intracerebral inoculation with the TYCSA strain of measles virus produced a significantly high titer of measles antibody in the CSF with a minimal rise in the serum antibody and resulted in a significant decrease in serum/CSF antibody ratios. Intracerebral inoculation of a neurotropic canine distemper virus, the Onderstepoort strain, into measles-immune monkeys caused production of both measles and distemper antibodies in the CSF. Inoculation of measles-immune monkeys intravenously with measles virus or intracerebrally with rubella virus, which has no antigenic relation to measles virus, failed to evoke a measles antibody response in the CSF. These results indicated that local production of measles antibody in the CSF was caused by a stimulus within the central nervous system of measles virus antigen or canine distemper virus antigen that partially cross-reacted with measles virus antigen as a secondary antibody response.

Establishment of a persistently infected cell line with Rinderpest virus.

Persistent infection of rinderpest virus in Vero cells was established and designated as VRP34. Virus specific antigens were present in nearly 100 per cent of the cells. Cytopathic effect (CPE) consisting of syncytium formation and vacuolation is a unique feature of VRP34. Spontaneously released virus mainly consisted of non-temperature-sensitive virus populations and was able to initiate persistent infection in both normal Vero and RK13 cells. The results indicate that mutation of virus is responsible for the establishment of persistent infection.