The target-specific drug release which is depending on the pH of the medium appears precious approach for increasing of drug selectivity and further efficacy in photodynamic diagnosis (PDD) and therapy (PDT) of cancer. A strongly hydrophobic Zn (II) phthalocyanine (ZnPc) along with its liposomal formulates belongs to the clinically approved phthalocyanines for cancer photodiagnosis PDD and PDT. Nevertheless closed to the ideal photo-physicochemical properties the planar molecular structure of ZnPc easily forms aggregates which finally limit the phototoxic effect. Different strategies are on hand, all aiming to minimize the formation of photo-inactive associates. At present time, the polymeric carrier systems are still under development as carrier systems for biomedical applications. The present work evaluated the efficiency of two recently proposed graft - copolymers namely polyimide (PI)-graft-polymethacrylic acid (PAT2 and PAT3) as vehicles of hydrophobic ZnPc. The potential of the proposed polymeric brushes with great number of carboxylic groups, for conformational changes in different pH media, can be used for ZnPc release as studied by fluorescence spectroscopy. Complexes developed were investigated in vivo on rat model system of gastric carcinoma lesions for photodiagnosis and photodynamic treatment of neoplasia and compared with the application of ZnPcs solely. The contrast achieved of the fluorescence detection using polymer brushes - phthalocyanine conjugate is about twice higher that standard applied photosensitizer using same protocol and doses of application. The photodynamic treatment efficacy was also significantly improved allowing to receive full response using doses of 0,5-1 mg/kg of the conjugates. |To obtain same efficiency for the ZnPc PDT in the gastric lesions treated drug doses of 1,5-2 mg/kg had to be applied. Initially detected fluorescence signal and photo-bleaching dynamics were used for the monitoring of the processes of accumulation and photodynamic treatment processes.
Transcranical photobiomodulation (tPBM, 1267 nm, 32 J/cm2) is effective non-invasive method for clearance of beta-amyloid from the brain in mice with Alzheimer’s disease and for improvemen of their neurological status.
Here in ex vivo (confocal imaging) and in vivo (optical coherent tomography) experiments on adult mice, we clearly demonstrate that the meningeal lymphatic drainage is an important mechanism for the brain clearing that might be also pathway for the brain clearing from metabolites and waste products that requests further detailed studies. Photodynamic effects stimulate the meningeal/cervical drainage opening new ideas for development of novel methods of activation of brain clearing that might be progressive strategies in therapy of neurovegetative diseases.
Gastric cancer often appears without preliminary symptoms that could be detected and recognized at early stages. Its diagnostic is sometime provided based on photodynamic techniques, although the latter are restricted by quite poor tumor selectivity. Due to this, additional experimental and data processing tools are required to improve diagnostic abilities. In this study we analyze how complexity measures can detect early changes in the normal gastric microcirculation. We apply a recently developed approach based on the multiscale entropy and show that the estimated measures of SampEn related to distinct ranges of scales enable the detection of early gastric cancer that is in accordance with the results of histological analysis.
This review highlights two opposing concepts of lymphatics and glymphatics, which are used to explain the drainage and cleansing functions of the brain. "Stumbling blocks" in two concepts and ways of compromise between them are discussed.
Stroke and traumatic brain injury are often associated with formation of brain edema, which is a potentially fatal pathological state provoking extensive accumulation of fluid in the brain tissues resulting in elevation of intracranial pressure and leading to impaired nerve function. There is only symptomatic anti-edema therapy is currently available. Therefore, the development of novel strategies to remove edema fluid is required. The brain edema is classified as vasogenic or cytotoxic edema, which associated with excess accumulation of fluid (edema) around capillaries resulting from disruption of the blood-brain barrier (BBB) or intracellular spaces (cell swelling) of the brain, respectively. In this brief review, we discuss possible mechanisms underlying brain edema formation and new strategies in development of novel of anti-edema drugs.
Here we present preliminary experimental data suggesting about involvement of the meningeal and cervical lymphatics in neurorehabilitation. Using model of hemorrhagic stroke, immunohistochemical analysis and atomic absorption spectroscopy, we clearly demonstrate the lymphatic clearance from the blood after stroke via the meningeal lymphatic vessels with further accumulation of hemosiderin and iron (products of disaggregated hemoglobin) in the deep cervical node (dcLN). The optical coherent tomography (OCT) was used for in vivo monitoring of accumulation of gold nanorods (92 nm in diameter) in the dcLN after their injection into the cisterna magna with the aim of mimicking of the brain clearance from of blood. The both ex vivo and in vivo data show the lymphatic clearance from subjects (the blood/GNRs) injected into the subarachnoid space that might be an important mechanism of neurorehabilitation after the intracranial hemorrhages.
The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.
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