RAFT Emulsion Polymerization as a Platform to Generate Well-Defined Biocompatible Latex Nanoparticles.

Current approaches to generate core-shell nanoparticles for biomedical applications are limited by factors such as synthetic scalability and circulatory desorption of cytotoxic surfactants. Developments in controlled radical polymerization, particularly in dispersed states, represent a promising method of overcoming these challenges. In this work, well-defined PEGylated nanoparticles are synthesized using reversible addition fragmentation chain transfer emulsion polymerization to control particle size and surface composition and were further characterized with light scattering, electron microscopy, and size exclusion chromatography. Importantly, the nanoparticles are found to be tolerated both in vitro and in vivo, without the need for any purification after particle synthesis. Pharmacokinetic and biodistribution studies in mice, following intraperitoneal injection of the nanoparticles, reveal a long (>76 h) circulation time and accumulation in the liver.

Enhanced Internalization of Indian Ayurvedic Swarna Bhasma (Gold Nanopowder) for Effective Interaction with Human Cells.

In the ancient traditional Indian Ayurvedic system of natural healing, gold nanoparticles (Swarna Bhasma, gold ash) have been used for its therapeutic benefits as far back as 2500 B.C. Ayurvedic medicinal preparations are complex mixtures that include many plant-derived products and metals. Bhasmas date as far back as the 8th century and are made by samskaras (processings), such as shodhana (purification and potentiation), jarana (roasting), and marana (incineration, trituration) in the presence of plant products, including juices and concoctions. Previous studies characterized the physical properties of gold ash, and the mechanisms of its entry into human cells, but only preliminary data exist on its toxicity. Before using nanoparticles for therapeutic application, it is extremely important to study their toxicity and cellular internalization. In the present study, various imaging techniques were used to investigate Swarna Bhasma's (gold nanopowder) toxicity in both cancerous and noncancerous cells (HeLa and HFF-1) and to characterize its spectral properties. The results showed that gold ash particles had no impact on the cellular viability of both HeLa and HFF-1 cells, even at high concentrations or long incubation times. Moreover, it was found that the internalization level of Swarna Bhasma to cells may be improved by mechanical breaking of the large aggregates into smaller agglomerates. Hyperspectral images revealed that after breaking, the small agglomerates have different spectral properties in cells, compared to the original aggregates, suggesting that size of particles is instrumental for the subcellular interaction with human cells.

Method for quantitative detection of FAM19A4 by flow cytometry using latex beads as solid carrier.

FAM19A4 (family with sequence similarity 19 member A4; also TAFA4) is a classical secretory protein expressed mainly in the central nervous system and upregulated significantly in lipopolysaccharide (LPS)-stimulated monocytes and macrophages. It is a novel cytokine ligand of formyl peptide receptor 1 (FPR1), showing chemotactic activities on macrophages and promoting the phagocytosis capacity and the release of reactive oxygen species (ROS) by macrophages upon zymosan stimulation. Based on the same detection principle as enzyme-linked immunosorbent assay (ELISA), we developed a sandwich immunoassay for quantitative detection of FAM19A4 in biological fluids by flow cytometry, with latex beads as solid carrier. The method showed good performance in a wide range of 39-10,000 pg/mL and possessed excellent specificity, good precision, and favorable recovery in several different matrices. Native FAM19A4 secreted by phorblo 12-myristate 13-acetate (PMA) and LPS stimulated THP-1 cells could also be detected by this method. This method will be much helpful to FAM19A4 studies.

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

BACKGROUND AND OBJECTIVES: The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. STUDY DESIGN/MATERIALS AND METHODS: Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. RESULTS: We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the amount of pressure used. When injecting 5% MB at 6 bars, the depth of infiltration reached 2.323 mm, while that at 8.5 bars reached 8.906 mm. The area of the hole created by the 5% MB injection was 0.797 mm(2) at 6 bars and 0.242 mm(2) at 8.5 bars. Latex injections reached a depth of 3.480 mm at 6 bars and 7.558 mm at 8.5 bars, and the areas were measured at 1.043 mm(2) (6 bars) and 0.355 mm(2) (8.5 bars). Histological examination showed that the injection penetrated as deep as the superficial musculoaponeurotic system at 6 bars and the masseter muscle at 8.5 bars. CONCLUSION: When injecting material into the skin using a pneumatic needle-free injector, higher-pressure injections result in a hole with smaller area than lower-pressure injections. The depth and shape of skin penetration vary according to the amount of pressure applied. For materials of low density and viscosity, there is a greater difference in penetration depth according to the degree of pressure. Lasers Surg. Med. 48:624-628, 2016. © 2016 Wiley Periodicals, Inc.

Testicular biodistribution of 450 nm fluorescent latex particles after intramuscular injection in mice.

The significant expansion in the use of nanoparticles and submicron particles during the last 20 years has led to increasing concern about their potential toxicity to humans and particularly their impact on male fertility. Currently, an insufficient number of studies have focused on the testicular biodistribution of particles. The aim of our study was to assess the distribution of 450 nm fluorescent particles in mouse testes after intramuscular injection. To this end, testes were removed from 5 groups of 3 mice each at 1 h (H1), 4 days (D4), 21 days (D21), 45 days (D45) and 90 days (D90) after the injection of 7.28 × 109 particles in the tibialis anterior muscles of each mouse. We examined histological sections from these samples by epifluorescence microscopy and confocal microscopy and identified testicular biodistribution of a small number of particles in groups H1, D4, D21, D45 and D90. Using CD11b immunostaining, we showed that particles were not carried into the testis by macrophages. The intratesticular repartition of particles mainly followed testicular vascularization. Finally, we found some particles in seminiferous tubules but could not determine if the blood-testis barrier was crossed.

Uptake, excretion and toxicity of nano-sized latex particles on medaka (Oryzias latipes) embryos and larvae.

Nanoparticles are particles with diameters of 100 nm or less. As the applications of these particles have increased in recent years, their potential impact on the physiology of humans and animals has also increased. However, little is known regarding the effect of nanoparticles on the physiology of aquatic organisms. In this study, we investigated the effect of nano-sized, fluorescent, latex particles on the freshwater fish, medaka (Oryzias latipes). Medakas were exposed to four different types of fluorescent latex particles and the uptake, excretion, and the effect of nanoparticle accumulation on survival rate in medaka larvae were examined. These are fluorescent latex particles, which are non-functionalized 50 and 500 nm in diameter and carboxyl-group functionalized 50 and 500 nm in diameter. Fluorescence intensity in fish embryos exposed to non-functionalized and carboxyl-group functionalized particles measuring 50 nm in diameter (Particle 50 nm and Particle c50 nm) was markedly higher compared to when embryos were exposed to particles measuring 500 nm in diameter (Particle 500 nm and Particle c500 nm). Moreover, the excretion of nano-sized particles (Particle 50 and Particle c50 nm) from embryos was considerably slow, compared to larger particles (Particle 500 and Particle c500 nm). In addition, the survival rate of larvae exposed to nano-sized particles in small cups was significantly lower than the survival rates of fish maintained in larger containers. The findings suggested that although the nano-sized fluorescent latex particles were not intrinsically toxic, a synergistic toxic effect arose in combination with other factors, which is not favorable for fish larvae.

Effect and distribution of contrast medium after injection into the anterior suprachoroidal space in ex vivo eyes.

PURPOSE: To determine the effects and posterior distribution of injections made into the anterior suprachoroidal space (SCS). METHODS: The anterior SCS of adult porcine and canine ex vivo eyes was cannulated. Latex injections and high frequency ultrasound (50 MHz) was used to image the effect and distension of the SCS. Flow characteristics and percentage maximal distribution of microbubble contrast injection into the SCS were assessed by 2D and 3D ultrasound. RESULTS: Mean (SD) distension of the SCS with PBS increased from 1.57 (0.48) mm after injection of 250 µL to 3.28 (0.57) mm with 1000 µL PBS. Eyes injected at physiologic IOP had no significant difference in SCS distension. In real-time 2D ultrasound, the contrast agent flowed from the injection site to the opposite ventral anterior SCS and the posterior SCS. Contrast arrived at the opposite and posterior SCS 7.8 (4.6) and 7.7 (4.6) seconds after injection, respectively. In sagittal images, contrast was visible in 24.0%to 27.2% of the SCS; in 10 of 12 eyes, contrast reached the posterior pole of the eye. In 3D images, contrast medium occupied 39.0% to 52.1% of the entire SCS. CONCLUSIONS: These results suggest that the SCS can expand, in a dose-dependent manner, to accommodate various volumes of fluid and that it is possible to image the SCS with ultrasound contrast. The authors' hypothesis that a single anterior SCS injection can reach the ocular posterior segment was supported. Further development of SCS injections for treatment of the ocular posterior segment is warranted.

Phospholipid-induced in vivo particle migration to enhance pulmonary deposition.

Amount of drug actually reaching the target region in the lung following pulmonary inhalation is often estimated at less than 10% for older devices. Current particle and device engineering technologies have improved on this but still fail to recover the "wasted" fraction of the drug and deliver it deeper into the lungs, which is generally desirable. FDA has approved several exogenous surfactants for prophylaxis and rescue treatment of respiratory distress syndrome (RDS). Their approved mode of administration (intratracheal instillation) and site of action (alveolar spaces) suggest that the phospholipids in the exogenous surfactants can spread from the trachea to alveolar air spaces and exert advantageous effects. We investigated whether in vivo lung migration of particles based on this phenomenon was possible and could be quantified based on changes in total and regional deposition of fluorescently labeled latex beads, utilized as an insoluble drug model. Following intranasal administration of beads, migration to rodent lungs was monitored upon intranasal instillation of Survanta (exogenous surfactant) or saline (control). After intranasal instillation approximately 12% of beads were found to migrate to the lung, and total lung deposition increased by approximately 10% on administration of Survanta or saline (control). After intranasal administration approximately 1% of beads in the lung were found to migrate to peripheral regions of the lungs, and a four- to six-fold increase in peripheral lung deposition was observed after Survanta instillation, compared to the saline control, which was determined to be independent of dose and volume of Survanta instillate in the range we studied. The in vivo rodent studies provided support for the idea that intranasally administered particles deposited in non-target lung locations may be translocated to peripheral sites in the lung therapeutically after surfactant application.

The effect of pH and organic ester penetration enhancers on skin permeation kinetics of terbutaline sulfate from pseudolatex-type transdermal delivery systems through mouse and human cadaver skins.

The purpose of this research was to prepare a pseudolatex transdermal delivery system for terbutaline sulfate and to evaluate the effect of pH and organic ester penetration enhancers on permeation kinetics of terbutaline sulfate through mice abdominal skin and human cadaver skin. An increase in the permeation flux by increasing pH was observed. The distribution coefficient of terbutaline sulfate between 1-octanol and buffers of different pH values was also pH-dependent. Furthermore, the change of the permeability coefficient with pH correlated well with the distribution coefficient by a 2-degree polynomial equation. The permeation profile and related kinetic parameters of terbutaline sulfate was determined in presence of 3 ester-type permeation enhancers incorporated in the films, viz methyl laureate, isopropyl lanolate, and isopropyl myristate. Among the 3, the more pronounced enhancing effect was obtained with isopropyl myristate, regarding the permeation flux, permeability coefficient, and diffusion coefficient. This was attributed to solubility parameter of isopropyl myristate being closer to the solubility parameter of human skin, and such a pronounced enhancing effect was probably caused by its passage across the skin barrier through the lipid pathway.

Penetration into solid tumor tissue of fluorescent latex microspheres: a mimic of liposome particles.

BACKGROUND: Using liposomes as a vehicle to transport anticancer drugs to cancer cells, to increase their effectiveness and decrease their toxicity, has been studied for many years. However, due to technical difficulties, the path of penetration for liposome particles into solid tumor tissue is still not clear. MATERIALS AND METHODS: In this report, rhodamine-labeled fluorescent latex microspheres were used as a model of liposome particles, combined with fluorescent staining of blood vessel CD31 and tumor cell nuclei. The penetration of microspheres from blood vessels in L1210JF solid tumors of mice was observed. After fluorescent latex microspheres were injected into tail vein, tumor tissue samples were collected at various times and cryosections were then made for fluorescent staining. RESULTS: Under fluorescence microscopy, the red fluorescent latex microspheres, the green fluorescent blood vessels and the blue tumor cells in the cancer tissue were seen clearly. The leaking of microspheres out from blood vessels was seen directly. CONCLUSION: The results confirmed that the tiny particles can only leak out through the holes of the broken blood vessels and spread out through the space in between the cells of the solid tumor.

Potential use of nanoparticles for transcutaneous vaccine delivery: effect of particle size and charge.

The aim of this study was to investigate the effect of size and charge on the permeation of nanoparticles through the skin as the first step in designing a transdermal vaccine delivery system. Fluorescent particles ranging in size and charge were applied to the surface of full thickness pig skin in a diffusion chamber and the receptor fluid was assayed to determine permeation. Fluorescence microscopy was used to visualise the skin after experiments. The results showed that only 50 and 500 nm particles that were negatively charged were able to permeate the skin. This provides evidence of the potential of nanoparticles as delivery vectors for antigens and DNA for the purpose of transdermal vaccination protocols. The results would indicate that negative particles with sufficient charge may be ideal carriers for this purpose.

Kinetics and dynamic evaluation of specific immunotherapy.

UNLABELLED: Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy. MATERIAL AND METHODS: We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy. RESULTS: The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic focalisations were present for all the patients, whereas bowel focalisations were only observed for the subcutaneous route of administration. Sublingual SIT did not induce axillary or intestinal inflammatory focalisations, even though the patients had swallowed the allergenic extract. The uptake coefficient in individualized areas corrected to the uptake coefficient background was also studied. CONCLUSIONS: For the subcutaneous route of administration, except for glutaraldehyde-modified allergen, the local inflammatory activity at the allergenic injection site was significantly higher in depth and was time dependent, maintaining activity even after complete disappearance of the erythema and/or wheal. These results express a prompt inflammatory involvement of the immune system with this allergenic therapy, which was unexpected until now. We also observed differences concerning allergic diseases, the type of allergenic extracts and routes of administration.

Glove powder's carrying capacity for latex protein: analysis using the ASTM ELISA test.

Glove donning powders carry latex proteins and disperse them into the workplace environment. We have used the ASTM D6499 ELISA to quantify the amount of latex antigen bound to and carried by glove powders. We could differentiate between a small amount of protein actually bound to the powders and a larger amount carried by the powder. Enhanced binding of a major allergen, Hev b 5, to the starch powders was demonstrated by Western blot. The D6499 ELISA is able to measure total latex antigen, soluble and powder bound, simultaneously without the need to centrifuge the samples.

Characterization of the interactions between polymethacrylate-based aqueous polymeric dispersions and aluminum lakes.

Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit RS 30 D, Eudragit L 30 D-55, and Eudragit NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles.

Spread of injectate during C6 stellate ganglion block and fascial arrangement in the prevertebral region: an experimental study using donated cadavers.

BACKGROUND AND OBJECTIVES: The precise fascial space through which the injectate spreads during stellate ganglion block (SGB) remains unclear. Recent studies using magnetic resonance imaging or computed tomography have suggested that the injectate is deposited around and/or within the longus colli muscle during SGB. However, a fascial space, close to the longus colli, is the most likely route of spread. We identified the prevertebral interlaminal space (PVILS), situated between the anterior and posterior laminae of the prevertebral layer of the fascia, as an important route for the spread of the injectate and as a potential pathway to the ganglion. The danger of downward spread of deep infections through this space has previously been recognized. METHODS AND RESULTS: Using the 6th cervical vertebra paratracheal approach technique, we performed experimental SGB with 10 mL latex on donated cadavers. Spreading of latex into the PVILS was observed in 45 of 52 (86.5%) cadavers that had been fixed with formaldehyde after death, and 5 of 8 (62.5%) fresh cadavers. In these experiments, the latex usually reached the ganglion via the PVILS (39 of 45 and 5 of 5, respectively). Moreover, after direct injection into the PVILS, latex reached the ganglion in 13 of a further 19 (68.4%) postmortem-fixed donated cadavers. CONCLUSION: These results suggest that the PVILS plays a critical role in the spread of injectate as well as being a potential pathway to the stellate ganglion during SGB.

Influencia del tipo de material (látex frente a silicona) y de los corticoides en la producción de fibrosis peritoneal por el tubo de kehr. estudio experimental en ratas / Influence of the type of material employed (latex versus silicone) and of corticosteroids on the production of peritoneal fibrosis due to the presence of a "T"-tube: experimental study in rats

Introducción. La producción de fístulas biliares tras la retirada del tubo de Kehr es un problema de la cirugía de la vía biliar que presenta una importancia aún mayor en el trasplante hepático. En su etiología se han barajado diversos factores, entre los que destacan la interferencia que puedan llegar a ocasionar, en el desarrollo del trayecto fibroso en torno al tubo, tanto el tipo de material utilizado (generalmente látex o silicona) como el tratamiento con corticoides que suele ser administrado a estos pacientes. Objetivos. Comparar el grado de adherencias peritoneales producidas por dos tipos de materiales de tubos en "T" (látex y silicona), y analizar la influencia que sobre aquéllas pueda tener la administración de corticoides. Material y métodos. Se han utilizado 50 ratas hembra distribuidas en cinco grupos (control, látex, silicona, látex más corticoides y silicona más corticoides) y se ha estudiado, mediante un sistema de puntuación, el grado de adherencias peritoneales producidas por un fragmento de tubo de Kehr colocado en el espacio subhepático de la cavidad peritoneal. Se calculó un índice de producción de adherencias, que se utilizó para comparar a los grupos entre sí. Resultados. El índice de producción de adherencias media ñ desviación estándar fue: grupo de látex: 6,7 ñ 1,4; grupo de silicona: 2,1 ñ 1,7; grupos de látex tratados con corticoides: 3,5 ñ 1,4, y grupo de silicona más corticoides: 1,2 ñ 1,3. Se encontraron diferencias al comparar los dos materiales (p < 0,001). La administración de corticoides redujo la producción de adherencias tanto en el grupo de látex (p < 0,001) como en el de silicona (p < 0,05). Conclusiones. Los tubos de silicona condicionan una menor formación de adherencias peritoneales postoperatorias que los de látex, y la administración de corticoides reduce dicha formación en ambos casos (AU)

Effect of colon carcinoma cell supernatants on cytokine production and phagocytic capacity.

The ability of colon carcinoma cells to produce IL-1 beta, IL-6 and TNF alpha, and the effect of tumor cell supernatants (sups) on the capacity of peripheral blood mononuclear cells to produce these three cytokines was examined. In addition, the effect of colon carcinoma cell sups on the engulfing capacity of phagocytic cells was detected. The results showed that IL-1 beta, IL-6 and TNF alpha levels were significantly higher in tumor cell sups compared with those of autologous colon mucosal cells obtained from healthy tissue. Tumor cell sups caused a decrease in both phagocytic capacity, and the number of latex particles engulfed by each individual cell.

Evaluation of percutaneous penetration of natural rubber latex proteins.

Latex allergy is recognized worldwide as a serious health risk. To date, exposure assessment and intervention strategies have focused primarily on respiratory protection; this work evaluates the potential role of dermal protein penetration in the development of latex allergy. In vitro penetration models using flow-through diffusion cells and both human surgical specimens and hairless guinea pig skin (CrL: IAF/HA) demonstrated iodinated latex proteins (ammoniated and non-ammoniated) penetrating into and through both intact and abraded skin. Although less than 1% penetration was observed with intact skin, up to 23% of latex proteins applied to abraded skin were recovered from receptor fluid within 24 h of exposure. Phosphoimaging of the concentrated effluent revealed proteins ranging in size from 3 to 26 kDa. Using a (3)H(2)O penetration assay to evaluate barrier integrity, the amount of latex protein penetration was found to positively correlate with the degree of dermabrasion. Immunohistochemistry of the skin localized latex proteins in the Langerhans cell-rich epidermis and in the dermis. Both in vitro penetration studies and immunohistochemistry supported the use of hairless guinea pig skin as a surrogate for human skin in evaluating latex protein penetration. In studies performed in vivo, 35% of hairless guinea pigs topically exposed to latex proteins (100 microg) 5 days per week for 3 months demonstrated elevations in latex-specific IgG1. The implication for these data is that the skin is not only a plausible route for latex sensitization but can be a major exposure route when the integument has been compromised.

Effect of solid and liquid diet on uptake of large particulates across intestinal epithelium in rats.

The effect of diet composition on the uptake of particulates across the gastrointestinal epithelium has been examined in fasted male weanling Sprague-Dawley rats by estimating the systemic uptake of orally administered 2-microns latex polystyrene microspheres. Using a tissue solubilization assay, particle transfer in animals maintained on a fluid diet was determined. A larger number of particles was transferred from the gut lumen to the internal organs, including the mesenteric lymph node, spleen, bone marrow, liver, kidney, and heart of animals fed solid pelleted diet than those maintained on a fluid-diet 4 hr after oral administration of particles. The increase in particle number in rats fed the solid diet was only statistically significant (P < 0.05) for brain tissue in the analysis for trend. However, the number of particles retained in the proximal region of the gut at the end of this period was greater in animals fed the fluid diet. This work demonstrates that diet composition is important in gastrointestinal transepithelial translocation of microspheres.

Demonstration and organization of duct-associated lymphoid tissue (DALT) of the main excretory duct in the monkey parotid gland.

Duct-associated lymphoid tissue (DALT) of the main excretory duct in the monkey parotid gland was first demonstrated by light microscopy and by transmission and scanning electron microscopy. The DALT included a follicular area, a parafollicular area and a specialized overlying epithelium with distinct fine-structural elements. There was usually a solitary lymphoid follicle located in the subepithelial area near the orifice of the parotid duct. The lymphoid follicles typically had a distinct germinal center. Numerous immune cells often infiltrated into the epithelium overlying the lymphoid follicle. The superficial epithelial cells of the DALT were larger and flatter than the ordinary duct epithelial cells, and had short irregular microvilli on their luminal surface. They were also in close contact with immune cells such as dendritic cells and lymphocytes. Goblet cells were rare in this area. In addition, bacteria, seen at the duct orifice, were sometimes taken up by the flattened epithelial cells near the orifice. Latex microspheres administrated as particulate antigens at the duct orifice were selectively taken up by the flattened epithelial cells and also by the intraepithelial dendritic cells of the DALT. These morphological findings suggest that the epithelial cells of the DALT in parotid glands take up antigens from the duct lumen and transport them to adjacent immune cells, and that the DALT in parotid glands may serve as one of the inductive sites in the common mucosal immune system.