Biomedical subjects

E Marchi

Publications and source records attributed to E Marchi.

At least 19 recordsLinked to original sources

PubMed2006

Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis.

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.

Animals↗

PubMed2006

Early positron emission tomography (PET) restaging: a predictive final response in Hodgkin's disease patients.

BACKGROUND: It is important to distinguish between responders to standard treatment and non-responders Hodgkin's disease (HD) patients. PATIENTS AND METHODS: Between June 2003-September 2004, in our institute, 40 newly-diagnosed patients with advanced stage HD were consecutively treated with ABVD chemotherapy for six cycles. All these patients underwent staging/restaging: computed tomography (CT) and positron emission tomography (PET) at time 0, PET after two cycles, CT and PET after four and six cycles. RESULTS: After two cycles (PET-2), the PET was negative in 28/40 (70%), positive in 8/40 (20%), and minimal residual uptake (MRU) was present in the remaining four (10%) patients. After treatment, among eight patients who were PET-2+, seven showed refractory disease and one had relapse after 3 months. All four patients with MRU at the PET-2 became PET- during the further four cycles and, after treatment, three were in complete response (CR) and one relapsed after 5 months. All 28 PET negative patients at the PET-2 remained PET negative and all of them were in CR after treatment. CONCLUSIONS: The PET use for early (after two cycles) response assessment in HD patients is a significant step forward and has the potential to help physicians make crucial decisions about further treatment.

Adolescent↗

PubMed2004

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Adolescent↗

PubMed2001

Diagnosis of late-infantile neuronal ceroid lipofuscinosis: a new sensitive method to assay lysosomal pepstatin-insensitive proteinase activity in human and animal specimens by capillary electrophoresis.

Batten disease, or human late-infantile neuronal ceroid lipofuscinosis (LINCL) is a familiar progressive degenerative disease affecting children, caused by a deficiency of a lysosomal proteinase (tripeptidyl peptidase I, TPP-I) and characterized by the accumulation of autofluorescent storage bodies in the brain and other tissues of the body. Current methodology used to diagnose this disease needs to be improved in order to have less invasive techniques with higher resolution and shorter assay time. In this report, we discuss the potential merits of micellar electrokinetic chromatography as an excellent tool that requires minute samples but offers high resolution and a short running time for monitoring TPP-I activity in human and animal specimens.

Aminopeptidases↗

PubMed2001

Cholesterol in the separation of transudates and exudates.

The Light criteria represent the most acceptable method to separate transudates and exudates. However, approximately 10% of patients with transudates, especially those with congestive heart disease, are misdiagnosed with these criteria. To improve diagnostic accuracy, many biochemical markers have been proposed as alternatives to differentiate transudates and exudates. Cholesterol has raised particular interest because only pleural fluid is needed, which makes blood samples unnecessary and simplifies the procedure. In most clinical studies, cholesterol has been shown to be as sensitive as the Light criteria, although it is less specific. Other randomized studies are necessary to determine the real potential value of pleural-fluid cholesterol measurements. Studies of pleural-fluid cholesterol are aimed at better understanding the mechanisms by which cholesterol enters the pleural cavity and its role in diseases. The ideal cutoff point of cholesterol to differentiate transudates and exudates is still unknown. Recently, aspects of the cholesterol turnover in diseases have raised great interest. Cholesterol generated great interest after it was related to coronary artery diseases. The involvement of cholesterol in the atherosclerotic process is well known, although its importance in body cavities is still unclear.

Cholesterol↗

PubMed2001

Experimental pleurodesis in rabbits induced by silver nitrate or talc: 1-year follow-up.

STUDY OBJECTIVE: To compare the pleurodesis results from the intrapleural injection of silver nitrate and talc slurry over an observation period of 12 months in rabbits. DESIGN: Rabbits were randomized to receive 2 mL of 0.5% silver nitrate or 400 mg/kg of talc slurry in 2 mL intrapleurally. Ten rabbits in each group were killed at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, and 12 months after intrapleural injection. The degree of gross pleurodesis and the amount of microscopic pleural fibrosis and inflammation were graded on a scale of 0 to 4. RESULTS: The mean +/- SEM gross pleurodesis score in the 70 rabbits that received silver nitrate was 3.34 +/- 0.08, which was significantly higher than the score of 2.32 +/- 0.09 in the 70 rabbits that received talc. The mean gross pleurodesis score was significantly higher at each of the observation times (p < 0.05), except at 2 months, in the rabbits that received silver nitrate. The pleurodesis was distributed throughout the thorax in the rabbits that received silver nitrate, while it was only in the ventral thorax in the rabbits that received talc slurry. The gross pleurodesis scores showed no tendency to decrease during the 12-month observation period in either treatment group. The persistence of talc in the pleural space did not lead to chronic inflammatory changes because the inflammation scores were similar in both groups at all observation times. The microscopic pleural fibrosis score tended to decrease with time in the silver nitrate group but not in the talc slurry group. CONCLUSIONS: The intrapleural injection of 2 mL of 0.5% silver nitrate produces a better pleurodesis than does the intrapleural injection of 400 mg/kg of talc slurry in rabbits. The pleurodesis induced by silver nitrate persists for at least 1 year. The efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.

Animals↗

PubMed2000

Mesothelial cell apoptosis is confirmed in vivo by morphological change in cytokeratin distribution.

Apoptosis of mesothelial cells has been demonstrated in vitro but not in vivo. To identify apoptotic pleural cells as mesothelial, we used cytokeratin as a marker and found a striking spheroid, aggregated appearance of cytokeratin in apparently apoptotic mesothelial cells. In in vitro studies, we found that the aggregated cytokeratin pattern correlated with apoptosis in primary mesothelial cells from mice, rabbits, and humans and was not seen with necrosis. In in vivo studies in mice, we then used this cytokeratin pattern to identify and quantitate apoptotic mesothelial cells. Apoptotic mesothelial cells were best harvested by pleural lavage, indicating that they were loosely adherent or nonadherent. Instillation of RPMI 1640 medium or wollastonite for 24 h induced apoptosis in 0.1 +/- 0. 1 (SE) and 1.0 +/- 0.7%, respectively, of all mesothelial cells recovered, whereas instillation of known apoptotic stimuli, crocidolite asbestos (25 microg) for 24 h or actinomycin D plus murine tumor necrosis factor-alpha for 12 h, induced apoptosis in 5. 1 +/- 0.5 and 22.4 +/- 4.5%, respectively (significantly greater than in control experiments, P < 0.05). By analysis of cytokeratin staining, mesothelial cell apoptosis has been confirmed in vivo.

Animals↗

PubMed2000

Silver nitrate is superior to talc slurry in producing pleurodesis in rabbits.

STUDY OBJECTIVE: The ideal agent for producing pleurodesis has not been identified. Although talc is the agent most commonly used at the present time, there are concerns about its safety. Silver nitrate is a possible alternative agent. The purpose of the present study was to compare the effectiveness of intrapleural silver nitrate and talc slurry in producing pleurodesis in rabbits. Additionally, the total amount of pleural collagen and the distribution of thick and thin collagen fibers were studied. DESIGN: Two groups of 10 rabbits received either 0.50% silver nitrate or 400 mg/kg talc in a total volume of 2 mL intrapleurally. The animals were killed 28 days after injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. Collagen was assessed with the van Gieson's and picrosirius stains. RESULTS: The macroscopic pleurodesis (scale, 0 to 4; mean +/- SEM) resulting from the intrapleural injection of silver nitrate (3.4+/-0.2) was significantly better (p<0.001) than that resulting from talc (1.6+/- 0.1). The mean degree of microscopic pleural fibrosis induced by silver nitrate (3.3+/-0.3) was significantly higher (p = 0.003) than that induced by talc (1.8+/-0.1). The mean amount of microscopic pleural collagen (van Gieson's) was significantly greater (p<0.001) in the rabbits that received silver nitrate (3.0+/-0.2) than in those that received talc (1.6+/-0.2). The distribution of thick and thin collagen fibers did not differ between the groups. CONCLUSIONS: We conclude that, in our rabbit model, intrapleural silver nitrate was more effective than talc in producing a pleurodesis.

Animals↗

PubMed1998

Effectiveness of ethanolamine oleate as a pleural sclerosing agent in rabbits.

The ideal pleural sclerosing agent should be easily administered, without significant side effects, inexpensive, and widely available. None of the agents presently used meets all of these criteria. Ethanolamine oleate (ETH) is a sclerosing agent used in the sclerotherapy treatment of varicose veins of the legs and esophagus. The objective of the present study was to assess the efficacy of ETH as a pleural sclerosant in rabbits. An additional objective was to assess if better results were obtained when dextrose 50% (D50) as opposed to saline was used as the diluent. Each group of 10 rabbits received a total volume of 2 ml intrapleurally. The eight treatments were as follows: (1) 2 ml saline; (2) 2 ml D50; (3) 25 mg ETH plus 1.5 ml saline; (4) 25 mg ETH plus 1.5 ml D50; (5) 50 mg ETH plus 1.0 ml saline; (6) 50 mg ETH plus 1 ml D50; (7) 75 mg ETH plus 0.5 ml D50, and (8) 100 mg ETH. The rabbits were sacrificed 28 days after the injection. The intrapleural instillation of ETH resulted in evident pleurodesis, which was dose-dependent; 100 mg ETH induced significantly (p<0.05) more adhesions than did any other treatment. The selection of the diluent had no effect on the pleurodesis. The microscopic examination of the right visceral pleura showed that the mean degree of fibrosis after 100 mg ETH was significantly (p<0.05) greater than that after the other solutions. The mean degree of pleural inflammation, lung inflammation and lung fibrosis was minimal in all the groups. From this study we conclude that undiluted ETH produces pleurodesis in our experimental model. At the doses used, the pleurodesis was less than that produced after talc, tetracycline derivatives or silver nitrate in the same model.

Analysis of Variance↗

PubMed1998

Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.

Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine.

Administration, Oral↗

PubMed1997

Lacidipine inhibits the activation of the transcription factor NF-kappaB and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells.

OBJECTIVE: The adhesion of monocytes to endothelium, an early event in atherosclerosis is mediated by cell adhesion molecules. Signal-transduction pathways for these binding molecules include the translocation of the transcription factor NF-kappaB; moreover, intracellularly generated oxygen-derived free radicals play a major role in this process. In this study we evaluated the extent to which lacidipine, a calcium antagonist with antioxidant properties, affects the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells, induced by different pro-oxidant signals such as oxidized low density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-alpha). METHODS: We incubated 5 micromol/l Cu2+-oxidized LDL and TNF-alpha (2 ng/ml) with human umbilical vein endothelial cells for 48 and 6 h, respectively. ICAM-1, VCAM-1 and E-selectin were measured by flow cytometry. NF-kappaB was evaluated by electrophoretic mobility shift assay. RESULTS: The incubation of 5 micromol/l Cu2+-oxidized LDL not only caused a dose-dependent increase in ICAM-1, VCAM-1 and E-selectin (P < 0.001), but also synergically increased their TNF-alpha-induced expression (P < 0.001). The addition of lacidipine to human umbilical vein endothelial cells significantly reduced the expression of ICAM-1, VCAM-1 and E-selectin induced by TNF-alpha alone or with oxidized LDL (P < 0.001). The reduction in adhesion molecule expression caused by lacidipine was paralleled by a significant fall in NF-kappaB translocation. CONCLUSIONS: The results suggest that lacidipine may have prevented NF-kappaB-mediated adhesion molecule expression by exerting its effects on oxygen-derived free radicals. The results support previous observations that lacidipine may have therapeutic effects in atherosclerosis.

Calcium Channel Blockers↗

PubMed1997

Mechanisms of pleural liquid formation in pleural inflammation.

Inflammatory processes are a major cause of pleural effusion. Besides being important clinically for diagnosis and treatment of patients with pleural effusions, studies of inflammatory pleural effusions shed light on the mechanisms of pleural liquid formation and also on general mechanisms of inflammation. In this current review, we have chosen papers within the past year that highlight aspects of clinical and research interest concerning inflammation and inflammatory pleural effusions. In some studies, investigators have investigated basic mechanisms of the roles of cytokines and adhesion molecules in inflammatory cell recruitment and leakage of liquid. In other studies, clinicians have attempted to measure inflammatory markers as a means of diagnosis. In light of these studies, we discuss the current understanding of inflammatory pleural effusions and suggest future avenues for exploration.

Adenosine Deaminase↗

PubMed1997

Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits.

We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.

Animals↗

PubMed1996

Capillary electrophoresis of heparin and dermatan sulfate unsaturated disaccharides with triethylamine and acetonitrile as electrolyte additives.

Capillary electrophoresis at constant voltage with the addition of triethylamine as electrolyte to a running buffer containing borate using fused-silica capillaries permits the complete resolution in less than 30 min of 11 standard heparin and 8 standard dermatan sulfate disaccharides, which represent degradation products of heparin and dermatan sulfate by specific lyases. Triethylamine influences the migration time of disaccharides by reducing both their electrophoretic mobility towards the anode and the electroosmotic flow towards the cathode. A modulated combination of these effects together with borate-disaccharide complex formation is responsible for separation, especially in the case of isomers which differ in the position of the sulfate groups. The addition of acetonitrile did not introduce any favourable effect in the separation of disaccharide mixtures. Under these conditions different dermatan sulfates were analysed to assess the source of the preparations.

Acetonitriles↗

PubMed1995

Heparin modulates proliferation and proteoglycan biosynthesis in murine mesangial cells: molecular clues for its activity in nephropathy.

Glycosaminoglycan administration has favourable effects on morphological and functional renal abnormalities in different models. The possibility that exogenous glycosaminoglycans modulate glomerular matrix synthesis was explored in both primary and SV40-MES13 murine mesangial cell cultures. On both cell types, both low-molecular-weight heparin and different glycosaminoglycans showed dose-dependent inhibition of proliferation and increase of 35SO4(2)-uptake. After 36 h the cell compartment contained a spectrum of 35S-molecules of less than 200 kDa; under heparin treatment, the two main 35SO4(2)-components (high and medium MW) increased by 16 and 37% respectively. Susceptibility to glycosidases revealed that heparin promotes the expression of heparan sulphate and increases that of chondroitin sulphate. Moreover, heparin modifies the expression of decorin and biglycan, involved in adhesion and fibrillogenesis, while not affecting perlecan. The extracellular matrix modulation in renal cells, for which the sulphation type and ratio of heparin are crucial, may thus explain the beneficial renal effects of heparin.

Animals↗

PubMed1995

Desmin 370, a low molecular weight dermatan sulfate, reduces the weight of preformed thrombi in rats made afibrinogenemic by ancrod.

Desmin 370 (D370), a low molecular weight dermatan sulfate, has been shown to induce a marked reduction of the weight of preformed venous thrombi in rats and rabbits by mechanisms that appeared largely independent of inhibition of thrombus accretion. In order to provide further support for such a mechanism, we exploited the defibrinating capacity of ancrod to obtain a thrombosis model characterized by the lack of thrombus growth and thus sensitive only to agents promoting thrombus lysis. Thrombus formation in anesthetized rats was induced by vena cava ligature. Injection of ancrod (5 U/kg) 5 h after induction of venous stasis caused a more than 95% reduction in plasma fibrinogen and prevented thrombus accretion as indicated by the lack of thrombus weight increase during the 3 h experimental period (12.2 +/- 0.6 vs 14.5 +/- 1 as compared to 12.6 +/- 0.6 vs 19.6 +/- 0.8, p < 0.01, in control rats) and by the almost complete (> 90%) inhibition of 125I-fibrin(ogen) binding to thrombi. Moreover, when ancrod was given 1 h before vena cava ligature, no thrombi were formed within 2 h whereas at the same time interval visible thrombi were present in all control rats. Administration of D370 (10 mg/kg) to thrombus bearing rats, 1 h after induction of afibrinogenemia, resulted in a significant reduction in thrombus weight (43% after 2 h, p < 0.01) which was only slightly lower than that recorded in normofibrinogenemic rats (54%). Enhancement of plasma fibrinolytic activity by ancrod had no influence on thrombus lysis and was not all affected by administration of D370.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod↗

PubMed1994

Improved intestinal absorption of an enteric-coated sodium ursodeoxycholate formulation.

A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycoursodeoxycholate were measured by specific enzyme immunoassay after oral administration of their sodium salts in an enteric-coated formulation at equimolar doses of 475 and 540 mg. The same subjects also received in separate experiments ursodeoxycholic acid, sodium ursodeoxycholate, and glycoursodeoxycholic acid in gelatin capsules. The mean area under the curve (mumol/L.hr) following administration of enteric-coated sodium ursodeoxycholate (45 +/- 8) was significantly higher than that of either ursodeoxycholic acid (26 +/- 5; P < 0.01) or sodium ursodeoxycholate (25 +/- 6; P < 0.001) administered in a conventional gelatin capsule. No differences were found when glycoursodeoxycholic acid was administered as an enteric-coated sodium salt or in acid form in gelatin capsules. Ursodeoxycholic was administered at a dose of 10 mumol/min/kg over 1 hr to bile fistula rats both intraduodenally (i.d.) and intravenously (i.v.). The experiment included administration of the sodium salt in solution and the acid as a suspension. A similar experiment was performed with glycoursodeoxycholic acid. The ratio of the amount recovered from bile in the i.d. to that in the i.v. experiment is almost 1 for the sodium salt of ursodeoxycholate in solution, while it drops to 0.55 for ursodeoxycholic acid. No differences were found between i.v. and i.d. administration when glycoursodeoxycholic acid was administered in acid form and as a soluble sodium salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy.

Previous studies have indicated that administration of glycosaminoglycans can prevent some of the morphological and physiological alterations which occur in experimental diabetic nephropathy. The aims of this study were to further elucidate the effect of these drugs on glomerular basement membrane permeability by dextran clearance studies, to test the ability of glycosaminoglycans to revert established diabetic nephropathy and to examine the effect of glycosaminoglycans on renal extracellular matrix synthesis. Five groups of Sprague-Dawley rats were studied for 12 months: two control groups (treated or untreated non-diabetic), three streptozotocin diabetic animal groups, two of which received a glycosaminoglycan formulation, one from the induction of diabetes and the other after the fifth month of diabetes. At five months the 35S-sulfate glomerular incorporation, albuminuria, glomerular basement membrane thickness and anionic charge density were determined. At 12 months albuminuria, renal collagen IV and perlecan mRNA levels, anionic and neutral dextran clearances, glomerular basement membrane morphometry, and mesangial cell proliferation were evaluated. We demonstrate that long-term administration of glycosaminoglycans prevents renal morphological and functional alterations in diabetic rats and appears to revert established diabetic renal lesions. Glycosaminoglycan administration modified renal matrix composition by the normalization of collagen gene expression and increasing glomerular 35S-sulfate incorporation.

Animals↗