ABSTRACT
In this study, we analyzed poly(L-lactide-co-glycolide) (PLGA) scaffolds modified with artificial extracellular matrices (aECM) consisting of collagen type I, chondroitin sulphate, and sulphated hyaluronan (sHya). We investigated the effect of these aECM coatings on proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSC) in vitro. We found that scaffolds were homogeneously coated, and cross-linking of aECM did not significantly influence the amount of collagen immobilized. Cell proliferation was significantly increased on cross-linked surfaces in expansion medium (EM), but was retarded on cross-linked and non-cross-linked collagen/sHya coatings. The alkaline phosphatase activity was increased on sHya-containing coatings in EM even without the presence of differentiation supplements, but was six to ten times higher in differentiation medium (DM) and comparable for cross-linked and non-cross-linked collagen/sHya. The highest amount of calcium phosphate mineral was deposited on day 28 on cross-linked collagen/sHya. Therefore, coatings of PLGA scaffolds with collagen/sHya promoted the osteogenic differentiation of hMSCs in vitro and might be an interesting candidate for the modification of PLGA for bone reconstruction in vivo.
Subject(s)
Cell Differentiation/drug effects , Collagen/pharmacology , Glycosaminoglycans/pharmacology , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Polyglactin 910/pharmacology , Tissue Scaffolds/chemistry , Adult , Alkaline Phosphatase/metabolism , Animals , Calcium/metabolism , Cell Adhesion/drug effects , Cell Count , Cell Proliferation/drug effects , Cell Shape/drug effects , Cells, Cultured , Coated Materials, Biocompatible/pharmacology , Densitometry , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Humans , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/enzymology , Microscopy, Electron, Scanning , Rats , Young AdultABSTRACT
The influence of the chain microstructure on release process of doxorubicin from polymeric matrices was analyzed. Aliphatic polyester copolymers with optimal chain microstructure, i.e. poly(glycolide-co-L-lactide, 15/85) (PGLA) and poly(glycolide-co-epsilon-caprolactone, 10/90) (PGCA) were synthesized for long-term doxorubicin delivery systems. Various release profiles from PGLA and PGCA matrices were obtained. The investigations revealed the most steadily doxorubicin release from PGCA matrices with 5% (w/w) of drug content. Degradation of matrices with and without drug was monitored by means of NMR spectroscopy and confirmed stability of degradation process. From PGCA matrices the increase of released doxorubicin amount was observed during first 60 days. On the contrary in case of matrices obtained from PGLA the delay of doxorubicin release was observed during first 50 days, what was caused by interaction of drug molecules with polylactide chain of polymer matrix. The interaction between doxorubicin molecules and polylactide chains was confirmed by IR spectroscopy. This fact can be used for designing of delivery systems consisting of combination of matrices with different microstructure of copolymer chains in order to adjust concentration of released doxorubicin and stabilization of drug release process.
Subject(s)
Antibiotics, Antineoplastic/chemistry , Brain Neoplasms/drug therapy , Doxorubicin/chemistry , Drug Carriers , Glioma/drug therapy , Lactic Acid/chemistry , Polyesters/chemistry , Polyglycolic Acid/chemistry , Animals , Antibiotics, Antineoplastic/therapeutic use , Cerebrospinal Fluid/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Doxorubicin/therapeutic use , Drug Compounding , Humans , Hydrolysis , Kinetics , Magnetic Resonance Spectroscopy , Molecular Conformation , Polylactic Acid-Polyglycolic Acid Copolymer , Solubility , Spectroscopy, Fourier Transform Infrared , Technology, Pharmaceutical/methodsABSTRACT
We assessed the rate of release of a model nucleoside (adenosine, 5%, w/w) from nine different lactide-glycolide or lactide-caprolactone polymers. The polymer discs were eluted every second day with an artificial cerebrospinal fluid at the elution rate roughly approximating the brain extracellular fluid formation rate. Adenosine in eluate samples was assayed by HPLC. Three polymers exhibited a relatively constant release of adenosine for over four weeks, resulting in micromolar concentrations of nucleoside in the eluate. This points to the necessity of further development of polymers of this types as intracerebral nucleoside delivery systems for local treatment of brain tumors.
Subject(s)
Polyesters/chemistry , Brain/metabolism , Chromatography, High Pressure Liquid , Kinetics , Polyesters/metabolismABSTRACT
In the Department of Otolaryngology, Medical Academy in Warsaw, 332 patients were surgically treated between 1986 and 1995 because of parotid gland tumors. In 275 cases benign tumors, in 57 cases--malignant tumors were observed. The majority of benign tumors were pleomorphic adenoma (61.45%) and lymphadenoma (22.54%); the majority of malignant tumors were adenocarcinoma (28%), adenoid cystic carcinoma (21%), mucoepidermoid carcinoma (15.78%). All patients with benign tumors were surgically treated, patients with malignant tumors were operated on and irradiated. The surgical procedure used superficial parotidectomy and total parotidectomy with preservation of facial nerve where possible. Ten patients required total parotidectomy with facial nerve resection because of malignant tumors, six patients had neck dissection performed. Of the 57 patients treated on account of malignant tumors 43 survived; 14 patients died of a local recurrence or generalization neoplasm disease.
Subject(s)
Adenocarcinoma/surgery , Otolaryngology , Parotid Neoplasms/surgery , Academic Medical Centers , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Catchment Area, Health , Female , Hospital Departments , Humans , Male , Middle Aged , Parotid Neoplasms/mortality , Poland , Retrospective Studies , Survival RateABSTRACT
The microspheres made of the copolymers of lactide and epsilon-caprolactone were used for the controlled release of progesterone and beta-estradiol. The copolymers contained 83-94% of l or d,l-lactide. The influence of the microstructure of lactidyl blocks in the copolymer chains on the drug release rate was studied. More uniform release rate was observed in the case of the copolymer derived from d,l-lactide as composed to l-lactide. For the copolymer containing 83-94% of d,l-lactide units the progesterone and beta-estradiol release rate in vitro was found to be practically constant within over 40 days. The in vivo studies performed on rats revealed that the period of constant release rate of beta-estradiol can be prolonged to about 70 days. The microspheres made of the applied poly-(d,l-lactide-co-epsilon-caprolactone) are the convenient system for long time release of steroids.
Subject(s)
Estradiol/administration & dosage , Estradiol/chemistry , Polyesters/chemistry , Progesterone/administration & dosage , Progesterone/chemistry , Animals , Chemistry, Pharmaceutical , Delayed-Action Preparations , Estradiol/pharmacokinetics , Male , Microspheres , Polyesters/administration & dosage , Polyesters/pharmacokinetics , Progesterone/pharmacokinetics , Rats , Rats, Wistar , StereoisomerismABSTRACT
In this study, four cases of patients with retrocochlear hearing loss are presented (acoustic neuroma, cerebellopontine angle tumour, the fourth ventricle region tumour, inflammatory or vascular lesions in the fourth ventricle region). Standard audiometric tests, auditory brainstem response and radiological examinations such as CT scan and MRI were performed in all patients. The abnormal ABR observed in all cases suggested retrocochlear hearing loss. The presence of retrocochlear disorders was confirmed by CT or MRI. The analysis of presented cases showed that the abnormal ABR results should be a sufficient basis for referring the patient to MRI examination.
Subject(s)
Brain Neoplasms/diagnosis , Cerebellar Neoplasms/diagnosis , Cerebellopontine Angle/pathology , Cerebral Ventricles/physiopathology , Cochlea/physiopathology , Evoked Potentials, Auditory, Brain Stem , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/physiopathology , Neuroma, Acoustic/diagnosis , Vestibulocochlear Nerve/physiopathology , Adult , Brain Neoplasms/complications , Cerebellar Neoplasms/complications , Female , Hearing Loss, Sensorineural/etiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroma, Acoustic/complications , Tomography, X-Ray ComputedABSTRACT
The authors presents 14 cases Wegener's granulomatosis diagnosed in ORL Clinic in Warsaw. Localisation of the disease, clinical manifestation and difficulties of histopathological examination was described, emphasizing the role of ANCA test (antineutrophil-cytoplasm antibodies).
Subject(s)
Granulomatosis with Polyangiitis/diagnosis , Adult , Aged , Antibodies, Antineutrophil Cytoplasmic/analysis , Female , Granulomatosis with Polyangiitis/pathology , Granulomatosis with Polyangiitis/therapy , Humans , Male , Middle AgedABSTRACT
We describe a 3 patients with Wegener's granulomatosis in remission while taking cyclophosphamide and prednisone who developed upper airway obstruction. The diagnosis was confirmed by parotid gland, pharynx, kidney biopsy. The stenosis developed in the area of previously noted tracheal ulceration and responded satisfactorily to bronchoscopic dilatation. Tracheotomy for progressive upper airway obstruction has remained the mainstay of treatment and was necessary in one of cases. We presented the others techniques of treatment subglottic stenosis-the surgical intervention and carbon dioxide laser photoresection. No antineutrophil cytoplasmic antibodies were found in the patients serum. These antibodies are of auxiliary value in recognizing Wegener's granulomatosis as well as in monitoring the activity of the disease process.
Subject(s)
Granulomatosis with Polyangiitis/complications , Laser Therapy , Tracheal Stenosis/complications , Tracheal Stenosis/surgery , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Carbon Dioxide , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Granulomatosis with Polyangiitis/drug therapy , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Male , Prednisone/administration & dosage , Prednisone/therapeutic use , Tracheal Stenosis/physiopathologyABSTRACT
Our previous work demonstrated that 12(S)-HETE, a lipoxygenase metabolite of arachidonic acid, promoted B16 amelanotic melanoma (B16a) cell spreading on fibronectin. In the current study, we investigated the biochemical mechanisms of the 12(S)-HETE induced response. 12(S)-HETE treatment resulted in a time-dependent increase in B16a cell spreading on fibronectin, which was blocked by either calphostin C or by genistein but not by H8. Two hours following cell plating, both spontaneous and 12(S)-HETE promoted cell spreading reached their maximum (nearly 100%). Spontaneous cell spreading was inhibited by the select 12-lipoxygenase inhibitor, BHPP, whose inhibitory effect could be overcome by increasing doses of exogenous 12(S)-HETE. 12(S)-HETE-treated B16a cells plated on either fibronectin or cultured on their own extracellular matrix demonstrated increased vinculin and tyrosine-phosphorylated proteins, which were colocalized at focal adhesions. The increase in vinculin localization to focal adhesions appeared to be a post-transcriptional process, since 12(S)-HETE treatment did not alter the overall protein level of vinculin in tumor cells, but resulted in a specific enrichment of vinculin to focal adhesions. Pretreatment of B16a cells with either calphostin C or genistein abolished 12(S)-HETE-increased formation of vinculin- and phosphotyrosine-containing focal adhesions. Immunoblotting using antiphosphotyrosine antibody 4G10 demonstrated, following 12(S)-HETE stimulation, an increased tyrosine phosphorylation of several proteins in focal adhesions; most prominently, a approximately 155 kd protein, a 120-130 kd protein cluster, a 76 kd protein, and a 42/44 kd complex. Immunoprecipitation with anti-phosphotyrosine antibody PY20 revealed increased tyrosine phosphorylation, post 12(S)-HETE stimulation, of proteins migrating at 120, 76, and 42/44 kd, of which the 120 kd protein co-migrated with pp125FAK. Immunoprecipitation with anti-FAK antibody BC-3 followed by immunoblotting with anti-phosphotyrosine antibody RC20H demonstrated a time-dependent hyperphosphorylation of pp125FAK. The present study suggests that 12(S)-HETE promoted melanoma cell spreading on fibronectin involves tyrosine phosphorylation of pp125FAK and protein kinase C- and tyrosine kinase-dependent focal adhesion formation.
Subject(s)
Cell Adhesion Molecules/metabolism , Fibronectins , Hydroxyeicosatetraenoic Acids/pharmacology , Melanoma, Amelanotic/pathology , Protein Kinase C/physiology , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/physiology , Tissue Adhesions/etiology , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid , Animals , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , Mice , Phosphorylation , Receptor, Insulin/metabolism , Tumor Cells, Cultured , Tyrosine/metabolismABSTRACT
A case of ceruminoma was described. The authors also presents actual opinions about glandular tumors of the middle and external ear, their classification and treatment.
Subject(s)
Ear Neoplasms/pathology , Ear, External/pathology , Ear, Middle/pathology , Neoplasms, Glandular and Epithelial/pathology , Adult , Ear Neoplasms/complications , Ear Neoplasms/surgery , Ear, External/surgery , Ear, Middle/surgery , Evoked Potentials, Auditory, Brain Stem , Hearing Disorders/diagnosis , Hearing Disorders/etiology , Humans , Male , Neoplasm Staging , Neoplasms, Glandular and Epithelial/complications , Neoplasms, Glandular and Epithelial/surgery , TympanoplastyABSTRACT
The authors presented a case of ethmoid glioma which had performed as nasal polyp. They also discussed about problems of classification and treatment this type of neoplasm.
Subject(s)
Bone Neoplasms/pathology , Ethmoid Bone/pathology , Glioma/pathology , Adult , Bone Neoplasms/surgery , Diagnosis, Differential , Ethmoid Bone/surgery , Glioma/diagnosis , Glioma/surgery , Humans , Male , Nasal Polyps/diagnosisABSTRACT
The parapharyngeal space, an area of complex anatomic relationships, is involved in a wide variety of benign and malignant neoplasms. This paper reported in managing 16 patients with parapharyngeal primary tumors. The cervical approach as surgical treatment was used in whole group. Recurrent tumors accounted for 4 of 16 cases. Discussion of the indications, surgical technique and select points to using this operative procedure is based on operative experience gained from these 16 patients.
Subject(s)
Neoplasm Recurrence, Local/surgery , Pharyngeal Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Mediastinal Neoplasms/surgery , Middle Aged , Neoplasm Recurrence, Local/mortality , Pharyngeal Neoplasms/mortality , Pharyngectomy/mortality , Survival RateABSTRACT
The authors present 26 cases of malignant lymphoma hospitalized in E.N.T. Clinic in Warsaw for the period of 1985-1994. Results of aspiration biopsy in all presented cases were not-diagnostic. Patients were hospitalized for further diagnostics. This fact caused prolongation of diagnostic procedure.
Subject(s)
Lymphoma/epidemiology , Aged , Biopsy, Needle , Female , Humans , Incidence , Lymphoma/diagnosis , Male , Middle Aged , Poland/epidemiology , Sex DistributionABSTRACT
Tracheobronchopathia osteochondroplastica (TO) is a rare disease with accumulation of bony and cartilaginous nodules in the tracheal and bronchial mucosa. In some cases rhinitis atrophica (ozena) has been associated. A case of TO coexisting with ozena and iron deficiency anaemia was described.
Subject(s)
Anemia, Hypochromic/complications , Osteochondrodysplasias/etiology , Rhinitis, Atrophic/complications , Tracheal Diseases/etiology , Calcinosis/diagnostic imaging , Female , Humans , Osteochondrodysplasias/diagnosis , Radiography , Tracheal Diseases/diagnosis , Tracheal Stenosis/etiologyABSTRACT
This study was conducted to investigate the differences between auditory brainstem responses--ABR recorded in men with temporary or permanent threshold shifts (TTS or PTS). Behaviorally, the tested ears showed insignificant differences in the hearing thresholds at frequencies in the range 0.25-8 kHz. The latency of waves I, III, V and interwave intervals I-III, III-V, I-V were analysed as functions of stimulus intensity. The comparisons between recordings obtained in groups with TTS and PTS showed significant differences in latencies of wave V at 90 dB nHl only. The latencies of waves I, III and interwave intervals were unaltered.
Subject(s)
Auditory Fatigue/physiology , Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Loss, Noise-Induced/physiopathology , Noise/adverse effects , Adult , Humans , Male , Reaction Time/physiologyABSTRACT
Two cases of Wegener's granulomatosis are presented. The first case due to improper diagnosis died five months following initial clinical symptoms. The second case was diagnosed basing on clinical findings. Cyclophosphamide produced a quick and full remission. Both cases illustrate the need of proper diagnosis and introduction of treatment.
Subject(s)
Glomerulonephritis/diagnosis , Granulomatosis with Polyangiitis/diagnosis , Lung Diseases/diagnosis , Vasculitis/diagnosis , Adult , Cyclophosphamide/administration & dosage , Diagnosis, Differential , Diagnostic Errors , Drug Therapy, Combination , Female , Glomerulonephritis/complications , Glomerulonephritis/drug therapy , Granulomatosis with Polyangiitis/drug therapy , Humans , Lung Diseases/complications , Lung Diseases/drug therapy , Male , Prednisone/administration & dosage , Vasculitis/complications , Vasculitis/drug therapyABSTRACT
The relationship between temporary threshold shift (TTS) and latency changes of auditory brainstem responses (ABR) induced by noise exposure was studied in 23 normal-hearing subjects. Shift in latency wave V at 40 dB nHL of stimulus intensity as a result of auditory fatigue showed no significant correlation with TTS at 4 kHz. The great intersubject variability of shifts in latency wave V as a result of auditory fatigue suggests that this shift may be a useful measure of individual susceptibility to noise.
Subject(s)
Auditory Fatigue/physiology , Brain Stem/physiology , Evoked Potentials, Auditory , Acoustic Stimulation , Adult , Audiometry, Evoked Response , HumansABSTRACT
The effects of auditory fatigue on auditory brainstem responses (ABR) were investigated in 23 normal-hearing subjects. ABR was recorded before and after exposure to fatiguing noise. Behaviourally, the auditory fatigue was tested using a temporary threshold shifts (TTS) paradigm. The latency of waves I, III, V and interwave intervals I-III, III-V, I-V were analysed as functions of stimulus intensity. In post-exposure recordings a threshold elevation, significant increase of all waves latency, increase of interwave-interval III-V at 40,50,60 dB nHL and unaltered intervals I-III, I-V were observed.