ABSTRACT
Lysosomal storage diseases (LSDs) is a group consisting of over 50 disorders caused mostly by dysfunctions of lysosomal proteins and resultant accumulation of particular compounds inside cells and extracellular volumes in affected organisms. Genetic diseases are among the most difficult targets for medical treatment. Nevertheless, understanding of molecular bases of LSDs made it possible to develop novel procedures of treatment, employing molecular medicine. Although various therapeutic approaches have been proposed, and some of them were introduced into clinical practice, none of them was found to be effective in correcting all symptoms in treated patients. Central nervous system and skeleton appear to be the most difficult targets to be improved. Therefore, a proposal appeared that perhaps no single therapeutic procedure may be fully effective in treatment of LSD patients, and only combination of two or more approaches could be a successful therapy. In this review, we present and discuss current stage of various combination therapies for LSDs, based on already available published data.
Subject(s)
Combined Modality Therapy , Lysosomal Storage Diseases/therapy , Animals , Combined Modality Therapy/methods , Humans , Lysosomal Storage Diseases/diagnosis , Lysosomal Storage Diseases/etiology , Lysosomal Storage Diseases/metabolismABSTRACT
BACKGROUND: Over 70-95% patients with PR3 ANCA pulmonary vasculitis present with upper respiratory tract symptoms or sings. Nasal cavity usually presents with obstruction and chronic refractory infections (rhinosinusitis) which commonly manifest as bloody discharge or crusting obstruction. Mucopurulent discharge may occur in the acute phase or remission, along with other symptoms suggesting sinusitis. Later on, saddle nose deformities can occur due to collapse of the nasal septum. Other common destruction areas are the maxillary ostia, erosion of the tubinates or damage of soft palate. OBJECTIVE: The aim of the study was to characterize pathologies of nasal and sinonasal CT scans in patients with PR3 pulmonary ANCA vasculitis and to establish the CT diagnostic criteria for WG. Between 2005-2009 sinonasal CT visualization was performed in 35 patients (19 female, 16 male) with PR3 ANCA positive WG. RESULTS: Bony destruction of the nasal cavity was revealed in 15 (42.8%), damage or distortion of the paranasal sinuses in 20 (57.1%), the mastoid cells in 7 (20%), and the orbits in 7 (20%) patients. Sclerosing osteitis of the nasal cavity and paranasal sinuses were observed in 11 (31.4%) and in 24 (68.5%), respectively. Bony thickening of the nasal cavity was shown in 5 (14.2%) patients and of the paranasal sinuses in 7 (20%) (unilateral in 2 and bilateral in 5 patients). Seven patients (20%) had orbital masses; all unilateral. Septal perforation was observed in 11 (31.4%) and saddle nose deformity in 7 (20%) patients. CONCLUSIONS: Maxillary sinuses are regions which are most frequently affected during the course of PR3 ANCA pulmonary vasculitis. CT imagines may be a useful supplement to clinical and activity scoring of WG disease with pulmonary involvement.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/analysis , Granulomatosis with Polyangiitis/pathology , Nasal Cavity/pathology , Paranasal Sinuses/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
A case of the tumor of the orbita is presented. It caused large exophthalmus and partial damage of orbital bones without any loss in the visual acuity in the 20-year period of increasing. Before operation a tumor of the lacrimal gland or an angioma was suspected. A histopathological examination of the whole removed tumor revealed the presence of mixed tumor cells.
Subject(s)
Eye Neoplasms/pathology , Lacrimal Apparatus/pathology , Exophthalmos/etiology , Eye Neoplasms/surgery , Female , Humans , Lacrimal Apparatus/surgery , Magnetic Resonance Imaging , Middle AgedABSTRACT
The studies of microsomal liver enzyme activity by means of a respiratory test with 14C-aminopyrine (ABT) were carried out in 20 patients with duodenal ulcer treated for eight weeks with famotidine. The respiratory test was performed before the introduction of treatment (group I), after four weeks of treatment (group II), and after eight weeks of treatment (group III). The mean value of the respiratory test before treatment was 5.32% of the dose/h. After four weeks of treatment with famotidine a significant decrease was found of the test value (x = 4.79% of the dose/h). An even stronger inhibitory action of famotidine on the microsomal system was shown after eight weeks of the treatment (x = 4.46% of the dose/h). These results evidence a depressive effect of famotidine on the activity of liver monooxygenases. In patients taking this drug, other drugs metabolised in the hepatocyte microsomal system should be used with high caution, as well as those which are known to be inhibitors of this system.
Subject(s)
Duodenal Ulcer/drug therapy , Famotidine/therapeutic use , Microsomes, Liver/enzymology , Adult , Duodenal Ulcer/metabolism , Female , Humans , Male , Middle AgedABSTRACT
The transforming growth factors are endogenous polypeptide substances having own cell receptors. Among them two main factors have been isolated--transforming growth factor alpha (TGF alpha) and beta (TGF beta). TGF alpha is secreted by activated proliferating hepatocytes and by certain neoplastic cells. It stimulates the synthesis of DNA and migration of hepatic epithelial cells. In chronic liver diseases it is produced in increased amounts and stimulates then proliferation and regeneration. TGF beta is released by non-parenchymal liver cells, thrombocytes, and neoplastic cells. It inhibits the synthesis of DNA in many cells, inhibits the synthesis of albumins and fibrinogen and regulates the production of acute phase proteins. In chronic liver diseases it increases the production of fibronectin and collagen, inhibiting at the same time their enzymatic breakdown. TGF beta participates in the development and progression of hepatic fibrosis.
Subject(s)
Liver Diseases/physiopathology , Transforming Growth Factors/physiology , Animals , Chronic Disease , HumansABSTRACT
Functioning of hepatocytes has been assessed with respiratory test with aminopyrine labelled with 14C radioisotope in patients with duodenal ulcer treated with ranitidine. Reversibility of changes in liver microsomal system at different intervals after the completion of therapy has also been evaluated. Altogether 30 patients with duodenal ulcer treated with ranitidine have been examined: prior to the treatment--group Ia, after one day of ranitidine administration--group Ib, within 4 weeks of therapy--group Ic, within 8 weeks of therapy--group Id, and one week after the completion of the treatment--group Ie, as well as after a 4-week follow-up period--group If. Significant decrease in the results of respiratory test has been noted in patients treated with ranitidine after both four and eight weeks. Activity of liver mono-oxidases approached baseline values after one week following the completion of therapy. The results of routine liver functioning tests in all patients of groups I and II have been within normal values. The obtained results suggest that patients treated with ranitidine should cautiously be given other medicines, especially those affecting liver functioning or metabolized in the liver.
Subject(s)
Duodenal Ulcer/enzymology , Microsomes, Liver/enzymology , Ranitidine/therapeutic use , Adult , Duodenal Ulcer/drug therapy , Female , Follow-Up Studies , Humans , Liver Function Tests , Male , Middle AgedABSTRACT
The functional status of hepatocytes was evaluated using the breathing test with 14C-aminopyrine in a group of patients with duodenal ulcer treated with cimetidine, and the reversibility of liver microsomal system activity changes was assessed at various time intervals after the completion of treatment with the above mentioned drug. Thirty patients with duodenal ulcer treated with cimetidine were examined: before the treatment (Ia), after one day of treatment (Ib), after four weeks of treatment (Ic), after eight weeks of treatment (Id), one week after completion of treatment (Ie), and four weeks after completion of treatment. A significant decrease was found of the value of the breathing test already after one day of treatment with cimetidine which was more pronounced after four and eight weeks of treatment. An impaired microsomal system activity was shown even one week after completion of the treatment with cimetidine. The obtained results indicate the necessity of caution when other drugs are administered to patients treated with cimetidine, and this refers particularly to drugs impairing liver function, or metabolized in this organ.
Subject(s)
Cimetidine/therapeutic use , Duodenal Ulcer/enzymology , Microsomes, Liver/drug effects , Adult , Aminopyrine , Breath Tests , Carbon Radioisotopes , Duodenal Ulcer/drug therapy , Female , Humans , Male , Middle AgedABSTRACT
The liver microsomal enzymes activity was measured by aminopyrine breath test in 20 subjects with duodenal ulcer disease treated with famotidine for 8 weeks. Aminopyrine breath test was performed, before treatment (group I), after 4 weeks of therapy (group II) and after 8 weeks of treatment with famotidine (group III). The mean aminopyrine breath test value before treatment was 5.32% dose/h. After 4 weeks of treatment with famotidine statistically significant decrease of breath test values (x = 4.79% dose/h) was found. More strong microsomal enzymes inhibition was found after 8 weeks of famotidine therapy (x = 4.46% dose/h). These data indicate an inhibitory effect of famotidine on liver monooxygenases activity. In patients taking this drug, treatment with other drugs metabolised in liver and with drugs inhibiting the microsomal system must be very cautions.
Subject(s)
Duodenal Ulcer/drug therapy , Duodenal Ulcer/enzymology , Famotidine/therapeutic use , Microsomes, Liver/enzymology , Adult , Aminopyrine , Breath Tests , Female , Humans , Male , Middle AgedABSTRACT
Assessment of the functional state of the liver microsomal enzymes with 14C-aminopyrine breath test (ABT) was performed in 42 patients with small cell lung cancer before treatment (group I), in 30 patients with small cell lung cancer treated with cytostatic drug after remission induction of Houston program (group II) and in 30 healthy volunteers of control group (group III). The classic liver tests were determined. Statistically low values of aminopyrine breath test in patients with advanced cancer (stadium III) were found. Values of ABT decreased further after the cytostatic drugs treatment. Abnormal results were found in 83% of patients in the group II. Values of classic liver tests in whole population (group I, II, III) were within normal limits. Abnormal values of ABT that indicate inhibition of aminopyrine demethylation may indicate early functional hepatocytes lesion after cytostatic treatment. This test should be done previously in patients needing treatment with other metabolised in liver or with microsomal system inhibitors.
Subject(s)
Carcinoma, Small Cell/enzymology , Lung Neoplasms/enzymology , Microsomes, Liver/enzymology , Adult , Antineoplastic Agents/therapeutic use , Breath Tests , Carcinoma, Small Cell/drug therapy , Female , Humans , Liver Function Tests , Lung Neoplasms/drug therapy , Male , Middle Aged , Reference ValuesABSTRACT
The effect of Triton X-100, sodium deoxycholate and saponin upon the solubilization of 5'-nucleotidase, the membrane enzyme derived from pig thyroid was studied. Triton X-100 at the concentration of 0.1% did not cause enzyme solubilization, whereas at the concentration of 1.0% it caused only partial release of the former from the membranes. Saponin (1.0% concentration) brought about a marked (about threefold) increase in the enzyme activity which resulted from the exposing active loci of the enzyme, however it did not cause total solubilization of it. 1% sodium deoxycholate increased the enzyme activity by 5 times and also caused its almost total solubilization (over 90%). The results indicate the 5'-nucleotidase is strongly bound to the cell membranes and the non-ionic detergents like Triton X-100 and saponin do not fit for the solubilization of this enzyme.
