Biodegradable Photonic Melanoidin for Theranostic Applications.

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

[Lymph node image with ultrasmall superparamagnetic iron oxide and comparison with pathological result].

OBJECTIVE: To assess the characteristics of enhanced magnetic resonance image with ultrasmall superparamagnetic iron oxide (USPIO) in the inflammatory and tumor metastatic rabbit model, and explore its relevance with histologic ultrastructural findings. METHODS: Totally 36 New Zealand white rabbits were randomly divided into lymphadenitis group and metastatic group. Complete Freund's adjuvant was injected into the bilateral dorsal footpads of 18 rabbits to set up ipsilateral lymphadenitis model. The other 18 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/ml) in both thighs to set up metastatic lymph node model. Magnetic resonance scan were performed 24 hours before and after USPIO (90 micromol Fe/kg) injection. T2 values of each lymph node were measured and lymph node T2 enhancement rate was calculated as well. HE staining, Prussian blue staining, and electronic microscopy were performed to observe the pathological microstructure changes and the distribution of the iron particle in lymph node. Relationship between lymph nodes USPIO enhancement and its microstructures were further analyzed. Results Thirty-six lymph nodes in lymphadenitis group showed different degrees of reactive hyperplasia. Twenty-six lymph nodes in metastatic group were invaded by tumor cell. Non-enhanced scan showed mild difference between T2 signal intensity of the two pathological lymph node types. After USPIO enhancement, inflammatory lymph nodes showed distinct T2 signal reduction at the center, and metastatic lymph nodes showed homogenous and faint T2 signal reduction. Enhancement rate of benign and malignant lymph nodes were 57.39% and 29.45% respectively (P < 0.01). HE staining and Prussian blue staining indicated USPIO particles located mainly in the macrophages at inflammatory lymphatic medulla, while paracortical area and cortical area contained relatively much less USPIO particles due to less macrophages distribution. MRI findings were correlated with the pathological results. Electronic microscopy also verified that the majority of USPIO particles were located in the numerous cytophagic bubbles of macrophages. Lymph nodes metastasis including 4 lymph nodes with completed structure destruction due to entire tumor infiltration, 19 lymph nodes with partially lymph node structure destruction but reduced USPIO-contained macrophage numbers or reduced USPIO particles in macrophages, and 3 lymph nodes with only localized foci tumor metastasis at subcapsular area. Conclusions USPIO enhancement pattern of different lymph nodes is closely related to distribution and functional status of the intra-node macrophages. It may affect the accuracy of the lymph node property diagnosis based on USPIO enhanced image.

The relation between the acupoint structures and the clinical therapeutic effects.

We performed a histological study upon the acupuncture points and their effectiveness of clinical treatment; the background was the clinic evidence that a multitude of points are used in treating a disease, but only some of which may have an efficacy, since the others did not. After a comparative histological and anatomic study, it comes out that those points, which are more effective from a structural point of view, identify a neural fibrillar concentration, a well developed capillary network and an increased mucopolysaccharides (MPS) concentration, in particular, acid mucopolysaccharides. The present paper presents histological data, which demonstrate the difference in the structure of the acupuncture points, postulating their specific influence on clinical treatment.

Regulating effect of Chinese herbal medicine on the peritoneal lymphatic stomata in enhancing ascites absorption of experimental hepatofibrotic mice.

AIM: To observe the regulatory effect of Chinese herbal medicine on peritoneal lymphatic stomata and its significance in treating ascites in liver fibrosis model mice. METHODS: Two Chinese herbal composite prescriptions were used separately to treat the carbon tetrachloride-induced mouse model of liver fibrosis. The histo-pathologic changes of the liver sections (HE and VG stainings) were observed. The peritoneal lymphatic stomata was detected by scanning electron microscopy and computer image processing. The changes of urinary volume and sodium ion concentration were measured. RESULTS: In the model group, lots of fibrous tissue formed in liver and extended into the hepatic lobules to separate them incompletely. In the treated and prevention groups, the histo-pathologic changes of liver was rather milder, only showed much less fibrous tissue proliferation in the hepatic lobules. The peritoneal lymphatic stomata enlarged with increased density in the experimental groups (diameter: PA, 3.07 +/- 0.69 microm; PB, 2.82 +/- 0.37 microm; TA, 3.25 +/- 0.82 microm and TB, 2.82 +/- 0.56 microm; density: PA, 7.11 +/- 1.90 stomata.1000 microm(-2); PB, 8.76 +/- 1.45 stomata.1000 microm(-2); TA, 6.55 +/- 1.44 stomata.1000 microm(-2)and TB, 8.76+/-1.79 stomata.1000 microm(-2)), as compared with the model group (diameter: 2.00+/-0.52 microm density: 4.45+/-1.05 stomata.1000 microm(-2)). After treatment, the urinary volume and sodium ion excretion increased in the experimental groups (PA, 231.28+/-41.09 mmol.L(-1); PB, 171.69 +/- 27.48 mmol.L(-1) and TA, 231.44 +/- 34.12 mmol.L(-1)), which were significantly different with those in the model group (129.33 +/- 36.75 mmol.L(-1)). CONCLUSION: Chinese herbal medicine has marked effects in alleviating liver fibrosis, regulating peritoneal lymphatic stomata, improving the drainage of ascites from peritoneal cavity and causing increase of urinary volume and sodium ion excretion to reduce the water and sodium retention, and thus have favorable therapeutic effect in treating ascites.

[Structure of the rat lymphoid organs after prenatal exposure to indomethacin during antigenic stimulation]. / Stroenie limfoidnykh organov krys posle prenatal'nogo vozdeistviia indometatsina pri antigennoi stimuliatsii.

Primary immune response of thymus and mesenteric lymph nodes to prenatal action of indomethacin was studied in one month rats. Indexes of cell reactions in the experimental rat thymus were found to coincide with control during all phases although blast transformation intensity was slightly reduced. In mesenteric lymph nodes primary immune response was suppressed which was connected with lymphocyte functional insufficiency. This is manifested through less intensive intercellular cooperation in the first phase, suppression of blast transformation in B lymphocytes in the second and decrease of functional activity of the node B zones in the third ones.

Ex vivo expansion of tumor-draining lymph node cells using compounds which activate intracellular signal transduction. II. Cytokine production and in vivo efficacy of glioma-sensitized lymphocytes.

We have investigated the anti-tumor activity of ex vivo activated and expanded T cells which had been sensitized in vivo to one of two different syngeneic rat glioma cell lines; D74 or RT-2. Rats were sensitized by inoculation of irradiated tumor cells into each hind foot pad. After 10 days, the tumor-draining lymph node (DLN) from each popliteal region was excised and prepared as a single cell suspension. Tumor-DLN lymphocytes were next activated overnight in RPMI-1640 medium containing 10% fetal bovine serum (FBS), Bryostatin-1 (5 nM), ionomycin (1 microM), and 20 U human recombinant interleukin-2 (IL-2) per ml. Culture for seven days in RPMI-1640 supplemented with FBS and IL-2 resulted in approximately 100-fold expansion of the lymphocyte population. Both D74- and RT-2-sensitized T cells constitutively secreted tumor necrosis factor-alpha, and both lymphocyte populations produced comparable amounts of the cytokine when co-cultured with either glioma cell line. Neither D74- and RT-2-sensitized effectors constitutively secreted gamma-interferon (gamma-IFN), but both populations produced gamma-IFN when exposed to either glioma cell line in vitro. D74-sensitized T cells released significantly more gamma-IFN than the RT-2 DLN lymphocytes. In vitro Chromium-release assays indicated that RT-2-sensitized T cells were more cytotoxic for RT-2 targets than for the D74 line and that D74-sensitized effectors were also more cytotoxic for RT-2 targets. To assess in vivo therapeutic efficacy, rats who had been inoculated intradermally with RT-2 cells three days earlier received an intravenous injection of RT-2- or D74-sensitized DLN cells (10(6) cells/gram body weight) expanded after activation with Bryostatin-1 and ionomycin or an equal number of lymphokine-activated killer (LAK) cells. Tumor diameters were measured daily and revealed that injection of glioma-sensitized lymphocytes led to the elimination of tumor while treatment with LAK cells had no therapeutic benefit. These results indicate, that at least for these two glioma lines, gamma-IFN release, rather than in vitro cytotoxicity, was a better predictor for in vivo immunotherapeutic efficacy of the glioma-sensitized, expanded T cells.

Lesions associated with mineral deposition in the lymph node and lung of the dog.

This report includes details of the clinical and pathologic features of 31 dogs with a range of systemic illness and granulomatous lymphadenopathy associated with the presence of birefringent crystalline material within lymph nodes. Similar crystalline material was found in the lymph nodes of dogs with lymphoma (n = 9) and as an incidental finding within the canine lung (n = 9). The mineral content of these crystals was determined by electron microprobe analysis and interpreted in light of the composition of known geological or human-made compounds. A wide range of elements was identified including silicon, sulfur, copper, calcium, and aluminium, with lesser proportions of phosphorus, sodium, potassium, iron, magnesium, titanium, nickel, and chromium. Many of these compounds may have originated from exogenous natural and human-made sources, but some compounds (notably phosphates and sulfates) are uncommon or not found in nature and may have been formed within the tissues of the body (biomineralization). The inflammatory response induced by the presence of these minerals within lymphoid tissue may trigger altered immunoregulation, accounting for the spectrum of disease observed.

[Effect of He-Ne laser acupuncture on lymph-nodes in rats].

The lymphocytes and antigen presenting cells in lymph node of rats stimulated by He-Ne laser acupuncture were observed by using TEM and SEM to investigate the ultrastructural changes of them. There were numerous activated T-cells which showed deeply indented nucleus, abundant small void mitochondria and free ribosomes in the paracortex area. The B-cells were gradually differentiated into large lymphocytes, immature and mature plasmatic cells which with a lot of rough endoplasmic reticulum. They were prominently increased in the pulp area. The macrophages had short processes with numerous folds and microvilli and tended to neighboring lymphocytes. The nucleus pores were increased. There were a lot of pinocytosomes, phagosomes, lysosomes in various size of macrophages. The bundles (5-6 nm in diameter) of microfilaments of the macrophages were extended from the cytoplasm to the processes. The interdigitating cells which contained the characterized single layer of rER, numerous polysomes, mitochondria and well-developed Golgi-complex were closed to macrophages and lymphocytes. In conclusion the activities of the cellular immunity and humoral immunity were enhanced by laser.

Effects of the adjuvant DEAE-dextran and Staphylococcus aureus on the lymph pathways and filtering capacity of popliteal lymph nodes in sheep.

The effects of subcutaneous injections of the adjuvant DEAE-dextran and, or killed Staphylococcus aureus on the structure of the lymph pathways of popliteal lymph nodes in sheep were examined using light and electron microscopy and Microfil casts. Dextran with or without killed S aureus caused significant changes in the lymph pathways both within the node and outside it. However, killed S aureus alone did not. The changes included anastomoses among afferent lymph vessels and between afferent and efferent lymph vessels; proliferation of vessels around the node; joining of parts of the capsule and trabeculae to adjacent parenchyma with loss of parts of the subcapsular and trabecular sinuses; enlargement of medullary sinuses; and reduction of the number of reticular processes in sinuses throughout the node. These changes were accompanied by a reduced ability of the node to filter chicken red blood cells labelled with chromium-51 which were injected into an afferent lymph vessel.

An electron microscopic study of the acupuncture or moxibustion stimulated regional skin and lymph node in experimental animals.

Ultrastructures of the electro-acupuncture or moxibustion stimulated skin and regional lymph nodes in experimental animals were examined by scanning and transmission electron microscopy. In the scanning electron microscopy, small numbers of infiltrating erythrocytes and lymphocytes were found in the vicinity of the penetrated acupuncture needle in the acupuncture-stimulated skin, whereas moxibustion-treated instances revealed a large number of immunocyte infiltrations in the region. Transmission electron microscopically revealed that immunocytes consisted of lymphocytes, monocytes and some granulocytes and mast cells. In addition, the moxibustion-stimulated regional lymph nodes increased in weight after the stimulation and induced numerous immunocyte influx through afferent lymphatics. The acupuncture-stimulated nodes, however, revealed no remarkable change in the weight and morphology. A functional significance of the acupuncture and moxibustion-stimulated skin and regional nodes was discussed in reference to previous immunohistological descriptions of immune-reacted lymph node of the same animals.

Staining reticulin in beef dorsal lymph nodes for electron microscopy.

Reticulin has been classically identified by virtue of its argyrophilia, as observed by light microscopy. The similiarity between reticulin and collagen has been a matter for considerable discussion. This paper describes the application of a silver-staining procedure which demonstrates the fine structure of these fibres when studied by electron microscopy, giving a direct indication of the morphological identity of the argyrophilic structures, i.e. reticulin, with collagen. Beef lymph node tissue was used for this study.