Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we determined the efficiency of magnetization transfer magnetic resonance imaging (MT-MRI) to differentiate native and enzymatically degraded cartilage, using bovine sesamoid bones from the metacarpophalangeal joint as a model system. Gradual proteoglycan (PG) depletion was achieved by increasing incubation periods with testicular hyaluronidase. For native cartilage a Ms/Mo ratio of 0.303 +/- 0.09 (mean +/- SEM) was measured. Biochemically determined PG diminution up to 50% correlated strongly (r = 0.953) with changes in the Ms/Mo ratio. Further PG loss is not reflected in an equally drastic Ms/Mo increase, whereas subsequent treatment of PG-depleted cartilage samples with collagenase led to an additional rise in the Ms/Mo ratio. Proteoglycan depletion and the beginning destruction of the collagen structure were also assessed histochemically. Our study confirms that collagen contributes to the baseline MT effect observed in articular cartilage. However, the changes in the MT ratio in gradually PG-depleted cartilage with a largely intact collagen network indicate that PG contributes to the MT effect as well. Therefore MT-MRI might become a sensitive technique for the monitoring of subtle degradational changes in articular cartilage, the still inaccessible process in osteoarthritis.
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PMID:Can magnetization transfer magnetic resonance imaging follow proteoglycan depletion in articular cartilage? 921 83

A case of malignant mesothelioma of the pleura and the peritoneum is reported. In April 1996, a 40-year-old men noticed sudden onset of back pain. Radiographic examinations and MRI revealed pleural effusions, ascites, ringed enhanced tumorous lesions in the right posterior diaphragm along the abdominal aorta, and marked thickening of the right diaphragm with moderate signal intensity. On thoracoscopic surgery, there were white small nodules on the intercostal parietal pleura. Tumor cells of a tubulopapillary pattern had large rounded nuclei and eosinophilic cytoplasms in a partially glandlike arrangement. Cytoplasms of tumor cells stained for alcian blue disappeared after hyaluronidase digestion. Immunohistochemical examinations showed positive staining for keratin but negative for CEA. Electron micrographs showed numerous long thin microvilli, desmosomes and intermediate tonofilaments. From these findings, malignant mesothelioma was diagnosed. The malignant mesothelioma cells of the pleura in this case were considered to disseminate the peritoneum directly through the diaphragm or its lymphatic canals. MRI and thoracoscopic surgery were useful for the demonstration of the pleural disseminations and abdominal invasions.
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PMID:[A case of malignant mesothelioma of the pleura and the peritoneum detected by sudden onset of back pain and pleural effusion and ascites]. 939 60

One of the attractions of molecular imaging using 'smart' bioactive contrast agents is the ability to provide non-invasive data on the spatial and temporal changes in the distribution and expression patterns of specific enzymes. The tools developed for that aim could potentially also be developed for functional imaging of enzyme activity itself, through quantitative analysis of the rapid dynamics of enzymatic conversion of these contrast agents. High molecular weight hyaluronan, the natural substrate of hyaluronidase, is a major antiangiogenic constituent of the extracellular matrix. Degradation by hyaluronidase yields low molecular weight fragments, which are proangiogenic. A novel contrast material, HA-GdDTPA-beads, was designed to provide a substrate analog of hyaluronidase in which relaxivity changes are induced by enzymatic degradation. We show here a first-order kinetic analysis of the time-dependent increase in R(2) as a result of hyaluronidase activity. The changes in R(2) and the measured relaxivity of intact HA-GdDTPA-beads (r(2B)) and HA-GdDTPA fragments (r(2D)) were utilized for derivation of the temporal drop in concentration of GdDTPA in HA-GdDTPA-beads as the consequence of the release of HA-GdDTPA fragments. The rate of dissociation of HA-GdDTPA from the beads showed typical bell-shaped temperature dependence between 7 and 36 degrees C with peak activity at 25 degrees C. The tools developed here for quantitative dynamic analysis of hyaluronidase activity by MRI would allow the use of activation of HA-GdDTPA-beads for the determination of the role of hyaluronidase in altering the angiogenic microenvironment of tumor micro metastases.
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PMID:Kinetic analysis of hyaluronidase activity using a bioactive MRI contrast agent. 1719 86

Tuberculous meningitis is primarily a disease of the meninges of brain and spinal cord along with adjacent brain parenchyma. The characteristic pathological changes are meningeal inflammation, basal exudates, vasculitis and hydrocephalus. Tuberculous meningitis has a strong predilection for basal parts of the brain. Exudates, if dominantly present in the interpeduncular, suprasellar and Sylvian cisterns, result in optochiasmatic arachnoiditis and tuberculoma. Optochiasmatic arachnoiditis and tuberculoma are devastating forms of tuberculous meningitis and often associated with profound vision loss. This clinical entity more frequently affects young adults. In a recent study, on the multivariate logistic regression analysis, female sex, younger age and raised cerebrospinal fluid protein content were identified as predictors for developing optochiasmatic arachnoiditis. Frequently, optochiasmatic tuberculoma and optochiasmatic arachnoiditis develop paradoxically while a patient is being treated with anti-TB drugs. MRI reveals confluent enhancing lesions that are present in the interpeduncular fossa, pontine cistern, and the perimesencephalic and suprasellar cisterns. Management of tuberculous optochiasmatic arachnoiditis and optochiasmatic arachnoiditis tuberculoma has been variable. Treatment of optochiasmatic arachnoiditis continues to be a challenge and the response is generally unsatisfactory. In isolated case reports and in small series, corticosteroids, methyl prednisolone, thalidomide and hyaluronidase have been used with variable success. The benefit from neurosurgery is controversial and deterioration may follow the initial temporary improvement. Management of paradoxical optochiasmatic arachnoiditis is also controversial. Some patients regain vision following treatment with anti-TB drugs and continued usage of corticosteroids. Neurosurgery may be considered in the patients with either treatment failure or when diagnosis is in doubt. In conclusion, presence of optochiasmatic arachnoiditis or tuberculoma has important therapeutic and prognostic implications for patients of tuberculous meningitis.
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PMID:Tuberculous optochiasmatic arachnoiditis: a devastating form of tuberculous meningitis. 2190 82

The development of multimodal in situ cross-linkable hyaluronic acid nanogels hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated in the hydrophobic domains of the hybrid hydrogel without leakage. However, hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This allows the utilization of imaging agents as tracers of the hydrogel degradation. UV-vis spectrometry and MRI studies reveal that the degradability of the hydrogels correlates with their structure. The hydrogels presented here are very promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic drugs, as well as imaging of hydrogel degradation and tracking of degradation products in vivo.
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PMID:Injectable in situ forming hybrid iron oxide-hyaluronic acid hydrogel for magnetic resonance imaging and drug delivery. 2486 75

Cosmetic injection of hyaluronic acid (HA) and other fillers is increasingly common, and the late complications of these relatively new procedures are now coming to medical attention. Three patients with delayed periocular swelling that began years after injection of HA are described, with CT, MRI, and histopathologic characterization. While HA fillers are marketed as having a temporary effect of several months, the authors demonstrate that they may persist in the body for up to 9 years. Unlike most previous reports, there was no inflammatory reaction or encapsulation, simply infiltration into more superficial subcutaneous layers. All cases improved after surgical biopsy and hyaluronidase injections. Delayed periocular swelling after filler injections from several years prior can mimic serious medical conditions. With a detailed history and high index of suspicion, one may avoid a costly and invasive workup.
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PMID:Delayed Superficial Migration of Retained Hyaluronic Acid Years Following Periocular Injection. 2590 86

Four derivatives of hyaluronic acid (HA) bearing thiol (HA-SH), hydrazide (HA-hy), 2-dithiopyridyl (HA-SSPy), and aldehyde groups (HA-al) respectively were synthesized. Thiol and 2-dithiopyridyl as well as hydrazide and aldehyde make up two chemically orthogonal pairs of chemo-selective functionalities that allow in situ formation of interpenetrating (IPN) disulfide and hydrazone networks simultaneously upon the mixing of the above derivatives at once. The formation of IPN was demonstrated by comparing it with the formulations of the same total HA concentration but lacking one of the reactive components. The hydrogel composed of all four components was characterized by a larger elastic modulus than those of the control single networks (either disulfide or hydrazone) and the three component formulations gave the softest hydrogels. Moreover, a hydrazone cross-linkage was designed to contain a 1,2-diol fragment. This allowed us to partially disassemble one type of network in the IPN leaving another one unaffected. In particular, treatment of the IPN with either sodium periodate or dithiothreitol resulted in disassembly of the hydrazone and disulfide networks respectively and thus softening of the hydrogel. Contrarily, the single network hydrogels completely dissolved under the corresponding conditions. In corroboration with this, enzymatic degradation of the IPN by hyaluronidase was also substantially slower than the degradation of the single networks. In order to further improve the mechanical properties of the elaborated injectable IPN, it has been in situ hybridized with iron oxide nanoparticles (IONPs). The mesh size of the IPN was smaller than the size of the IONPs resulting in the retention of nanoparticles in the matrix under equilibrium swelling conditions. However, these nanoparticles were released upon enzymatic degradation suggesting their use as MRI tags for non-invasive tracking of the hydrogel material in vivo. Additionally, this injectable hybridized hydrogel with encapsulated IONPs can be used in hyperthermia cancer therapy.
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PMID:In situ forming interpenetrating hydrogels of hyaluronic acid hybridized with iron oxide nanoparticles. 2624 66

Current clinical research into mild traumatic brain injury (mTBI) has focused on white matter changes as identified by advanced MRI based imaging techniques. However, perivascular tau accumulation in the brains of individuals diagnosed with mTBI suggests that the vasculature plays a key role in the pathology. This study used a rat model to examine whether the endothelial glycocalyx, a layer of the vasculature responsible for sensing luminal shear forces, is damaged by exposure to repeated low intensity blast, and whether this layer is associated with observed behavioral deficits. The blast exposure used consisted of 12, 40 kPa blast exposures conducted with a minimum of 24 h between blasts. We found that repeated blast exposure reduced glycocalyx length and density in various brain regions indicating damage. This blast exposure paradigm was associated with a mild performance decrement in the Morris water maze (MWM) which assesses learning and memory. Administration of hyaluronidase, an enzyme that binds to and degrades hyaluronan (a major structural component of the glycocalyx) prior to blast exposure reduced the observed behavioral deficits and induced a thickening of the glycocalyx layer. Taken together these findings demonstrate that the endothelial glycocalyx degradation following repeated blast is associated with behavioral decrements which can be prevented by treatment with hyaluronidase.
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PMID:Repeated Low Intensity Blast Exposure Is Associated with Damaged Endothelial Glycocalyx and Downstream Behavioral Deficits. 3192 May 75

Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (Mn3O4) and hematite (Fe3O4) nanoparticle (GMF). The highly stable HART nanoassembly has enhanced CD44-mediated intracellular uptake along with hyaluronidase (hylase) and redox-responsive drug-gene release. With Bcl-2 gene silencing induced by the successful delivery of HART in multidrug-resistant MCF7 breast cancer cells, the synergistic cytotoxic effect of Bcl-2 silencing and DOX was achieved. In addition, the HART nanoassembly containing GMF exhibited excellent dual MRI contrast (T1/T2) by reducing artifact signals. Overall, the HART nanoassembly with its enhanced theranostic properties has the potential to improve the therapeutic efficacy in future preclinical and clinical trials.
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PMID:Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells. 3092 64

Background and Objectives: The purpose of this retrospective study was to identify predictors of short-term outcomes associated with a lumbosacral transforaminal epidural steroid injection (TFESI). Materials and Methods: The medical records of 218 patients, who were diagnosed with lumbosacral radiculopathy and treated with a TFESI, were reviewed in this retrospective study. A mixture of corticosteroid, lidocaine, and hyaluronidase was injected during TFESI. Patients with >50% pain relief on the numerical rating scale compared with the initial visit constituted the good responder group. Demographic, clinical, MRI, and electrodiagnostic data were collected to assess the predictive factors for short-term outcomes of the TFESI. Results: A multivariate logistic regression analysis demonstrated that a shorter duration of symptoms and a positive sharp wave (PSW)/fibrillation (Fib) observed in electrodiagnostic study (EDx) increased the odds of significant improvement 2-4 weeks after the TFESI. Conclusions: Shorter duration of symptoms and PSW/Fib on EDx were predictors of favorable short-term response to TFESI.
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PMID:Factors Predicting Favorable Short-Term Response to Transforaminal Epidural Steroid Injections for Lumbosacral Radiculopathy. 3110 45


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