carbocyanines and Chronic-Disease

A pH-sensitive near-infrared fluorescent probe with alkaline pKa, AlkaP-1, was developed by incorporating a benzoyl hydrazine group into a cyanine dye. The significant fluorescence changes in the alkaline regions enable the probe to monitor the alkalization process from acute wounds to chronic wounds in diabetic mice.

Topics: Animals; Carbocyanines; Cell Line, Tumor; Chronic Disease; Diabetes Mellitus, Experimental; Fluorescent Dyes; Humans; Hydrazines; Hydrogen-Ion Concentration; Infrared Rays; Mice, Transgenic; Optical Imaging; Wounds and Injuries

Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells and endothelial cells associated with obliteration of small pulmonary arterioles and formation of plexiform lesions. To date, no curative treatments have been identified for pulmonary arterial hypertension. There are various therapeutic options, including conventional medical therapies and oral, subcutaneous, intravenous, and inhalation delivery. We have previously shown that miR-143/145 knockout can prevent the development of chronic hypoxia-induced pulmonary hypertension (PH) in mice. Here, we use chronic hypoxia-induced PH as a disease model to evaluate miR-143/145 inhibition after delivery of antimiRNAs via the subcutaneous or intranasal routes. We use qRT-PCR and immunofluorescence to confirm that both delivery strategies efficiently inhibit miR-143/145 in lung tissue from mice with chronic hypoxia-induced PH.

Topics: Administration, Intranasal; Animals; Antagomirs; Carbocyanines; Chronic Disease; Disease Models, Animal; Female; Fluorescent Antibody Technique; Gene Transfer Techniques; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Mice, Inbred C57BL; MicroRNAs; Real-Time Polymerase Chain Reaction

Idiopathic pulmonary fibrosis is a devastating disease characterized by a progressive, irreversible, and ultimately lethal form of lung fibrosis. Except for lung transplantation, no effective treatment options currently exist. The bleomycin animal model is one of the best studied models of lung injury and fibrosis. A previous study using mouse tumor models observed that liposome-encapsulated bleomycin exhibited reduced lung toxicity. Therefore, we hypothesized that airway delivery of synthetic phosphatidylcholine-containing liposomes alone would protect mice from bleomycin-induced lung toxicity. C57BL/6 mice were administered uncharged multilamellar liposomes (100 μl) or PBS vehicle on day 0 by airway delivery. Bleomycin (3.33 U/kg) or saline vehicle was then given intratracheally on day 1 followed by four additional separate doses of liposomes on days 4, 8, 12, and 16. Fluorescent images of liposomes labeled with 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate confirmed effective and widespread delivery of liposomes to the lower respiratory tract as well as uptake primarily by alveolar macrophages and to a lesser extent by type II alveolar epithelial cells. Results at day 22, 3 wk after bleomycin treatment, showed that airway delivery of liposomes before and after intratracheal administration of bleomycin significantly reduced bleomycin-induced lung toxicity as evidenced by less body weight loss, chronic lung inflammation, and fibrosis as well as improved lung compliance compared with controls. These data indicate that airway-delivered synthetic liposomes represent a novel treatment strategy to reduce the lung toxicity associated with bleomycin in a mouse model.

Topics: Administration, Inhalation; Animals; Bleomycin; Carbocyanines; Chronic Disease; Female; Fluorescent Dyes; Intubation, Intratracheal; Liposomes; Lung; Mice; Mice, Inbred C57BL; Pneumonia; Pulmonary Fibrosis; Weight Loss

The present study was carried out to determine the effects of a combined peripheral phrenicotomy and rostral spinal cord hemisection on the synaptic architecture in the ipsilateral rat phrenic nucleus. Young adult female Sprague-Dawley rats were divided into a hemisection-alone and two hemisection-plus-phrenicotomy (HPP) groups. In all animals, DiI, a fluorescent carbocyanine dye was injected into the left hemidiaphragm to retrogradely label the ipsilateral phrenic motoneurons. In the HPP groups, left intrathoracic phrenicotomies were carried out at 2 and 4 weeks prior to sacrificing. Hemisection-alone animals were not subjected to phrenicotomy. In all animals, a left C2 spinal cord hemisection was performed 24 h prior to death. Quantitative morphometric analysis of the phrenic nucleus showed that the number of synapses contacting phrenic profiles is significantly less in the HPP (2 week) group as compared to the hemisection-alone group, but this number returns to a level not significantly different from the hemisection-alone value in the HPP (4 week) group. The results suggest that the transient change in the number of synapses might contribute to the differential expression of the crossed phrenic phenomenon documented in another group of animals subjected to the same surgical procedures. Furthermore, the different stages of glial reaction induced by phrenicotomy/spinal cord hemisection might underlie the change in synaptic number.

Topics: Animals; Carbocyanines; Cell Size; Chronic Disease; Cordotomy; Dendrites; Electrophysiology; Female; Fluorescent Dyes; Microscopy, Electron; Motor Neurons; Neuronal Plasticity; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Synapses