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Biomedical subjects

G Münch

Publications and source records attributed to G Münch.

At least 37 records · Page 2Linked to original sources
PubMed2001

Advanced glycation end products (AGEs)-induced expression of TGF-beta 1 is suppressed by a protease in the tubule cell line LLC-PK1.

BACKGROUND: Advanced glycation end products (AGEs) are assumed to play a key role in diabetic nephropathy (DN). Since little is known about their action in tubule cells, we investigated in LLC-PK1 cells: (i) whether AGE-bovine serum albumin (AGE-BSA) affects cell proliferation and expression of transforming growth factor-beta (TGF-beta 1); and (ii) whether the AGE-induced effects can be modulated by trypsin due to interference with its binding proteins at the cell surface. METHODS: Arrested cells were exposed to vehicle (control), AGE-BSA (19--76 microM) and BSA (38 microM) in the presence or absence of trypsin (0.625--5.0 microg/ml) (2.5 microg/ml) for 24 h. We evaluated cell proliferation by cell count and by [(3)H]thymidine incorporation, TGF-beta 1 expression by reverse transcription-polymerase chain reaction (RT-PCR), and TGF-beta 1 protein by ELISA. In addition, cell accumulation of AGEs was studied by immunohistochemical staining of the AGE imidazolone. RESULTS: AGE-BSA inhibited [(3)H]thymidine incorporation, lowered cell number and increased cell protein content as well as TGF-beta 1 mRNA and protein as compared with control and BSA. Immunohistochemical staining revealed a marked intracellular accumulation of the AGE imidazolone. Co-incubation of AGE-BSA with trypsin ameliorated the impaired thymidine incorporation, the decreased cell count and the enhanced cell protein content. TGF-beta 1 overexpression was normalized, while TGF-beta 1 protein declined insignificantly. Intracellular imidazolone accumulation was strikingly suppressed. CONCLUSIONS: In the tubule cell line LLC-PK1, AGE-BSA exerts an antiproliferative effect, most probably due to TGF-beta 1 overproduction. The co-administration of trypsin abrogated this alteration, very likely as a result of an interaction with AGE-binding protein(s), which is supported by the decreased intracellular AGE accumulation. These findings may be the starting point for the development of specific proteolytic enzymes to interfere with the interaction between AGEs and their receptors/binding proteins.

Animals↗
PubMed2000

Evaluation of sympathetic nerve terminals with [(11)C]epinephrine and [(11)C]hydroxyephedrine and positron emission tomography.

BACKGROUND: The goal of the present study was to directly compare the new radiopharmaceutical agent [(11)C]epinephrine (EPI) with [(11)C]hydroxyephedrine (HED) through the use of PET. METHODS AND RESULTS: Seven healthy volunteers and 10 patients were investigated after heart transplantation. PET images of both tracers were of excellent quality in the volunteers. Values for radiolabeled metabolites (measured in percent of blood activity) at 5, 20, and 60 minutes after injection were approximately 35%, approximately 82%, and approximately 86% for EPI and approximately 13%, approximately 47%, and approximately 78% for HED, respectively. At 35 minutes, metabolite-corrected mean myocardial retention fraction of EPI (0. 235+/-0.022 min(-1)) was significantly greater (P<0.01) than that of HED (0.142+/-0.012 min(-1)). Corrected tracer retention fractions of both EPI and HED were significantly reduced in transplant recipients (0.055+/-0.004 min(-1), P<0.0001; and 0.050+/-0.006 min(-1), P<0. 0001, respectively) compared with volunteers. Normalization of retention fractions of patients with transplantation within 1 year to volunteers resulted in a value (ratio expressed in percent) of 20. 6+/-1.8% for EPI, significantly (P<0.03) smaller than 27.8+/-0.8% for HED. In patients with transplantation later than 1 year, the values were 26.0+/-2.9% for EPI compared with 44.2+/-5.6% for HED (P<0.014). CONCLUSIONS: Both tracers showed high selectivity for neuronal uptake in the heart, with a significant reduction in tracer retention in transplant recipients compared with volunteers. Compared with HED, EPI showed greater retention in volunteers and a lower retention ratio in transplant recipients, suggesting that EPI may be the superior tracer with higher sensitivity to neuronal abnormalities. Because EPI reflects neuronal uptake, metabolism, and storage, it may be more suitable for the study of neuronal integrity than HED, which primarily traces uptake-1 capacity.

Adult↗
PubMed2000

Isoform expression of the sarcoplasmic reticulum Ca2+ release channel (ryanodine channel) in human myocardium.

The Ca2+ release channel of the sarcoplasmic reticulum (SR) is essential for the release of Ca2+ from intracellular stores and is expressed widely in various excitable cells. It plays a key role particularly in excitation contraction coupling in myocytes in skeletal and cardiac muscle. Three isoforms of the SR Ca2+ release channel have been cloned. Recently coexpression of different isoforms was reported in different animal species and various tissues. In human cardiac tissue, however, isoform expression is not yet established. Therefore the aim of this study was to characterize isoform expression of the SR Ca2+ release channel in the human heart. We examined specific isoform expression of mRNA and proteins of the SR Ca2+ release channel in the four different chambers of the heart and the interventricular septum from explanted human hearts from nonfailing organ donors (n=8). Reverse transcriptase PCR from total cardiac RNA with isoform specific primers and western blots from myocardial homogenates with isoform specific antibodies were performed. Quantification of protein expression was achieved by densitometric scanning and computer analysis and is expressed as densitometric units per microgram of protein. A single band DNA signal was detected by reverse transcriptase PCR for the skeletal isoform 1 and the cardiac isoform 2 and isoform 3 in all regions of the human heart investigated. Specific protein expression was detected in all five myocardial regions of the human heart in western blots for the skeletal isoform I and cardiac isoform 2, and a weaker specific band was also detectable for isoform 3 of the SR Ca2+ release channel. Quantification of protein expression showed significant (P=0.008) lower expression of isoform 1 in the right ventricle (42+/-4 densitometric units/g tissue) and similar expression in all other regions (right atrium 58+/-3; septum 51+/-5, left atrium 54+/-5; left ventricle 51+/-6). Isoform 2 of the SR Ca2+ release channel was also significantly lower (P=0.001) in the right ventricle (33+/-4 densitometric/g tissue) and similar in the other heart chambers (right atrium 42+/-5: septum 41+/-3, left atrium 52+/-6, left ventricle 42+/-3). Differences in isoform 3 of the SR Ca2+ release channel for the various myocardial regions did not reach significant levels (right atrium 45+/-6, right ventricle 38+/-5, septum 49+/-8, left atrium 46+/-7, and in left ventricle 45+/-3 densitometric units/g tissue). In conclusion, all three isoforms of the SR Ca2+ release channel were determined in the human heart at both mRNA and protein levels with different quantitative expression in the different heart chambers. Coexpression of the three different isoforms with different functional properties might increase the complexity of regulation of excitation contraction coupling in the human heart in a chamber specific mode.

Adult↗
PubMed2000

Crosslinking of alpha-synuclein by advanced glycation endproducts--an early pathophysiological step in Lewy body formation?

An excess of reactive carbonyl compounds (carbonyl stress) and their reaction products, advanced glycation endproducts (AGEs), are thought to play a decisive role in the pathogenesis of neurodegenerative disorders and Parkinson's disease (PD) in particular. Accumulation of AGEs in various intracellular pathological hallmarks of PD, such as Lewy bodies, densely crosslinked intracellular protein deposits formed from neurofilament components and alpha-synuclein, have already been described in patients in advanced stages of the disease. There is, however, no indication of the involvement of AGE-induced crosslinking of alpha-synuclein in very early stages of the disease. In this study, we observed that AGEs and alpha-synuclein are similarly distributed in very early Lewy bodies in the human brain in cases with incidental Lewy body disease. These cases might be viewed as pre-Parkinson patients, i.e. patients who came for autopsy before the possible development of clinical signs of PD. AGEs are both markers of transition metal induced oxidative stress as well as, inducers of protein crosslinking and free radical formation by chemical and cellular processes. Thus, it is likely that AGE promoted formation of Lewy bodies reflects very early causative changes rather than late epiphenomenons of PD.

Aged↗
PubMed2000

Transition metal-mediated glycoxidation accelerates cross-linking of beta-amyloid peptide.

beta-Amyloid deposits, hallmarks of Alzheimer's disease, contain both sugar-derived 'advanced glycation end products' (AGEs) and copper and iron ions. Our in vitro experiments using synthetic beta-amyloid peptide and glucose or fructose show that formation of covalently cross-linked high-molecular-mass beta-amyloid peptide oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions. Formation of these covalent AGE cross-links can be inhibited by capping agents of amino groups, redox-inactive metal chelators and antioxidants, suggesting that these drugs may be able to slow down the formation of insoluble beta-amyloid deposits in vivo and possibly the progression of Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

[Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis]

Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis. HISTORY AND ADMISSION FINDINGS: A 60-year-old woman was admitted for the diagnosis of pulmonary infiltrates. A year before she had been exposed to tuberculosis when working as a doctor in Manila, the Philippines. Ten days before admission she had spent 10 days in Sao Paulo, Brazil. On admission she complained of fatigue, dry cough and nocturnal sweating. Her body temperature was 37.8; C. At auscultation of the chest fine rales were heard with diminished percussion sounds over both lungs. INVESTIGATIONS: The chest radiogram showed bilateral apical infiltrates. Blood count indicated normal white and red cells, but platelets were raised to 606 x 10 9/l. The differential blood count revealed an eosinophilia of 30%, ESR was raised at 91 mm/h and C-reactive protein increased to 103 mg/l. Angiotensin-converting enzyme, IgG, IgA, IgM, IgE, C3 and C4, paraproteins, antinuclear antibodies and double-strand DNA antibodies were all within normal limits. There was no direct or indirect evidence of tuberculosis and no parasites were found in sputum, stool, urine and blood. DIAGNOSIS, TREATMENT AND COURSE: After bronchoscopy with bronchial biopsy had failed to establish a diagnosis, an open lung biopsy with partial lung resection was performed. This revealed histologically an eosinophilic pneumonia with intra-alveolar protein precipitation and multinucleated giant cells, as well as interstitial fibroblast proliferation without demonstrable mincroorganisms. Under cortisone administration there was striking improvement of symptoms within a few days, and C-reactive proteins fell to 3 mg/l, ESR to 25 mm/h and the eosino-philia to 2%. CONCLUSION: Eosinophilic pneumonia should be included in the differential diagnosis of unclear pulmonary infiltrations with eosinophilia, once parasitological and malignant diseases, tuberculosis and allergic pulmonary aspergillosis have been excluded.

Journal Article↗
PubMed2000

SERCA2a activity correlates with the force-frequency relationship in human myocardium.

The present investigation addresses whether protein expression and function of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban (PLB) correlate in failing and nonfailing human myocardium. SERCA2a activity and protein expression, PLB phosphorylation, and the force-frequency relationship (FFR) have been determined in right atrium (RA) and left ventricle (LV) from nonfailing (NF, n = 12) and terminally failing [dilated cardiomyopathy (DCM), n = 12] human hearts. Only in LV of DCM hearts was SERCA2a activity significantly decreased [maximal turnover rate (V(max)) = 196 +/- 11 and 396 +/- 30 nmol. mg(-1). min(-1) in LV and RA, respectively], whereas protein expression of SERCA2a in the different chambers was unchanged in NF (3.9 +/- 0.3 and 3.2 +/- 0.4 densitometric units in LV and RA, respectively) and DCM hearts (4.8 +/- 0.8 and 3.4 +/- 0.1 densitometric units in LV and RA, respectively). Phosphorylation of PLB was higher in LV than in RA in NF (Ser(16): 180.5 +/- 19.0 vs. 56.8 +/- 6.0 densitometric units; Thr(17): 174.6 +/- 11.2 vs. 37.4 +/- 8.9 densitometric units) and DCM hearts (Ser(16): 132.0 +/- 5.4 vs. 22.4 +/- 3.5 densitometric units; Thr(17): 131.2 +/- 10.9 vs. 9.2 +/- 2.4 densitometric units). SERCA2a function, but not protein expression, correlated well with the functional parameters of the FFR in DCM and NF human hearts. Regulation of SERCA2a function depends on the phosphorylation of PLB at Ser(16) and Thr(17). However, direct SERCA2a regulation might also be affected by an unknown mechanism.

Adult↗
PubMed2000

Low-molecular but not high-molecular advanced glycation end products (AGEs) are removed by high-flux dialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) display very high levels of advanced glycation end products (AGEs). These compounds are suspected to play a pathophysiological role in diabetic nephropathy and late diabetic cardiovascular complications. We investigated to what extent AGE levels can be reduced by high-flux dialysis. PATIENTS AND METHODS: Ten ESRD patients were treated three times each with DIAPES and HF60, two different synthetic, high-flux hemodialysis membranes. The kinetics of AGE removal was studied by fluorescence spectroscopy (excitation 370 nm/ emission 440 nm) and by ELISA of serum samples and the removal of beta2-m was studied by immunonephelometry of plasma samples. Samples were taken during dialysis sessions at t = 0, 30 and 180 min. In addition, molecular weight distribution of AGE products in serum of three patients was analyzed by gel filtration and fluorescence detection. RESULTS: A significant difference could be found when AGE levels in serum of controls (n = 10) were compared with serum AGE levels of ESRD patients (p < 0.01/fluorescence; p < 0.0001/ ELISA). After 3 h of dialysis AGE-related fluorescence in serum decreased by 25.5 +/- 6.8% for HF60 (p < 0.0001) and 24.3 +/- 6.9% tor DIAPES (p < 0.0001). The corresponding decline measured by ELISA was 23.3 +/- 8.9% for HF60 (p < 0.0001) and 26.1 +/- 7.0% for DIAPES (p < 0.0001). Both methods showed no significant differences for both types of dialysis membranes. Gel filtration revealed that the decrease of fluorescence can be attributed to the removal of AGE peptides with a molecular mass < 12 kDa, only. In the high molecular range (> 12 kDa) no removal but hemoconcentration was observed independent of the dialyzer type used. The reduction of beta2-m during 3 hours of dialysis was 61.8 +/- 6.9% for HF60 (p < 0.0001) and 161.7 +/- 7.0% for DIAPES (p < 0.0001). CONCLUSION: Both high-flux dialyzers were equally effective to remove low-molecular AGE products, while AGE-modified proteins of higher molecular weight were only marginally affected. On the basis of our data we suggest the study of molecular mass-dependent uremic toxicity of AGEs and the examination of the influence of other treatment modalities on the level of high-molecular AGEs.

Adult↗
PubMed1999

N(2)-(1-Carboxyethyl)deoxyguanosine, a nonenzymatic glycation adduct of DNA, induces single-strand breaks and increases mutation frequencies.

N(2)-(1-Carboxyethyl)deoxyguanosine (CEdG) is a major nonenzymatic glycation product of DNA. The effect of CEdG modification, which was specifically prepared by incubation with dihydroxyacetone, on plasmid DNA topology was evaluated by gel electrophoresis. A time-dependent decrease of supercoiled plasmid-DNA was observed in parallel to the increase of CEdG adducts; the half-life time of the supercoiled plasmid-DNA was estimated to be approximately 16-18 h. CEdG-modified plasmid DNA showed a 25-fold reduced transformation efficiency. When modified DNA was used to transform Escherichia coli cells, a 6-fold increase in mutation frequency was determined by measuring loss of alpha-complementation. For the mutator strain BMH71-18mutS, an 8-fold increase in mutation frequency was observed. Although the exact mechanism of DNA damage is unclear, the occurrence of spontaneous depurination is likely. These findings suggest that a defined DNA glycation reaction can lead to DNA damage in vivo.

DNA Adducts↗
PubMed1999

Experimental induction of AGEs in fetal L132 lung cells changes the level of intracellular cathepsin D.

The effect of the carbonyl compound glyoxal on the induction of advanced glycation end products (AGEs) in the fetal epithelial lung cells L132 was investigated using immunohistochemical, immunoelectron microscopic, and biochemical methods. It was found that glyoxal treatment resulted in morphological changes of the cells and in the membranous and cytosolic localization of AGEs such as methyl-glyoxal-derived compounds, N-(carboxymethyllysine) (CML) and imidazolone. The formation of AGEs was accompanied with a change in the intracellular expression of cathepsin D and a loss of enzymatic activity.

Antibodies↗
PubMed1999

High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappaB activation and cytokine expression.

Advanced glycation endproducts (AGEs), which accumulate on long-lived proteins and protein deposits (amyloids), induce the expression of proinflammatory cytokines through NF-kappaB-dependent pathways. Hyaluronic acid with a molecular weight above 1.2 MDa (HMW-HA) inhibits the AGE-induced activation of the transcription factor NF-kappaB and the NF-kappaB-regulated cytokines interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha. Since the molecular weight of hyaluronic acid in humans decreases with age and under conditions of oxidative stress, it is likely that the protective effect of HMW-HA against AGE-induced cellular activation is lost at sites of chronic inflammation and in older age.

Animals↗
PubMed1999

Reduced Ca(2+)-sensitivity of SERCA 2a in failing human myocardium due to reduced serin-16 phospholamban phosphorylation.

It is still a matter of debate, whether decreased protein expression of SERCA 2a and phospholamban (PLB), or alterations in the phosphorylation state of PLB are responsible for the reduced SERCA 2a function in failing human myocardium. Thus, in membrane preparations from patients with terminal heart failure due to idiopathic dilated cardiomyopathy (NYHA IV. heart transplants) and control hearts (NF), SERCA 2a activity was measured with an NADH coupled assay with as well as without stimulation with protein kinase A (PKA). The protein expression of SERCA 2a, PLB and calsequestrin as well as the phosphorylation status of PLB (Back-phosphorylation technique: Serine-16-PLB specific antibody) were analysed using Western blotting technique and specific antibodies. In NF, the maximal activity (Vmax) and the Ca(2+)-sensitivity of SERCA 2a activity were significantly higher compared to NYHA IV. Protein expression of SERCA 2a, PLB and calsequestrin were unchanged, whereas both, the phosphorylation status of PLB as well as serine-16-PLB-phosphorylation, were significantly reduced in NYHA IV. After stimulation with PKA only the Ca(2+)-sensitivity, but not Vmax increased concentration-dependently. Therefore, in human myocardium, the Ca(2+)-sensitivity but not the Vmax of SERCA 2a is regulated by cAMP-dependent phosphorylation of phospholamban at position serine-16. Threonine-17-PLB-phosphorylation or direct phosphorylation of SERCA 2a may be candidates for regulation of maximal SERCA 2a activity in human myocardium.

Adult↗
PubMed1999

Investigations on oxidative stress and therapeutical implications in dementia.

Alzheimer's disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death and formation of amyloid plaques and neurofibrillary tangles (NFTs) NFTs are composed of hyperphosphorylated tau protein, and senile plaques contain aggregates of the beta-peptide. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Advanced glycation endproducts (AGEs), which are formed by a non-enzymatic reaction of glucose with long-lived protein deposits, are potentially toxic to the cell, are present in brain plaques in AD, and its extracellular accumulation in AD may be caused by an accelerated oxidation of glycated proteins. The microtubuli-associated protein tau is also subject to intracellular AGE formation. AGEs participate in neuronal death causing direct (chemical) radical production: Glycated proteins produce nearly 50-fold more radicals than non-glycated proteins, and indirect (cellular) radical production: Interaction of AGEs with cells increases oxidative stress. During aging cellular defence mechanisms weaken and the damages to cell constituents accumulate leading to loss of function and finally cell death. The development of drugs for the treatment of AD remains at a very unsatisfying state. However, pharmacological approaches which break the vicious cycles of oxidative stress and neurodegeneration offer new opportunities for the treatment of AD. Theses approaches include AGE-inhibitors, antioxidants, and anti-inflammatory substances, which prevent radical production. AGE inhibitors might be able to stop formation of AGE-modified beta-amyloid deposits, antioxidants are likely to scavenge intracellular and extracellular superoxide radicals and hydrogen peroxide before these radicals damage cell constituents or activate microglia, and anti-inflammatory drugs attenuating microglial radical and cytokine production.

Aged↗
PubMed1999

Amino acid specificity of glycation and protein-AGE crosslinking reactivities determined with a dipeptide SPOT library.

Advanced glycation end products (AGEs) contribute to changes in protein conformation, loss of function, and irreversible crosslinking. Using a library of dipeptides on cellulose membranes (SPOT library), we have developed an approach to systematically assay the relative reactivities of amino acid side chains and the N-terminal amino group to sugars and protein-AGEs. The sugars react preferentially with cysteine or tryptophan when both the alpha-amino group and the side chains are free. In peptides with blocked N-terminus and free side chains, cysteine, lysine, and histidine were preferred. Crosslinking of protein-AGEs to dipeptides with free side chains and blocked N termini occurred preferentially to arginine and tryptophan. Dipeptide SPOT libraries are excellent tools for comparing individual reactivities of amino acids for nonenzymatic modifications, and could be extended to other chemically reactive molecules.

Amino Acid Sequence↗
PubMed1998

cAMP-dependent protein kinase A-stimulated sarcoplasmic reticulum function in heart failure.

It is unclear whether decreased protein expression of SERCA2 (SR-Ca(2+)-ATPase) and phospholamban (PLB), or alterations in the phosphorylation state of PLB leading to increased inhibition of SERCA2 are responsible for the reduced SERCA2 function in failing human myocardium. In crude membrane preparations from patients with terminal heart failure due to idiopathic dilated cardiomyopathy (DCM) and control hearts (NF), SERCA2 activity was measured with a NADH coupled assay. Protein expression of SERCA2 and PLB and the phosphorylation state at the two phosphorylation sites, serine-16-PLB and threonine-17-PLB, were investigated with specific (phosphorylation) antibodies and Western blot technique. In NF, the Vmax and the Ca2+ sensitivity of SERCA2 activity were significantly higher compared to DCM. Protein expression of SERCA2 and PLB were unchanged, whereas the phosphorylation status at both serine-16-PLB and threonine-17-PLB were significantly reduced in DCM. The native phosphorylation status of PLB measured by the back-phosphorylation technique was reduced in DCM as well. After stimulation with protein kinase A only the Ca2+ sensitivity, but not Vmax, increased. The reduced phosphorylation state of PLB may lead to decreased Ca2+ sensitivity of SERCA2 in failing human myocardium. The altered regulation of the SR-CA(2+)-ATPase in human heart failure may offer an opportunity for an improvement in the therapy of heart failure.

Calcium-Binding Proteins↗
PubMed1998

Advanced glycation endproducts are associated with Hirano bodies in Alzheimer's disease.

One of the structural posttranslational modifications contributing to the formation of insoluble, and protease-resistant protein deposits in Alzheimer's disease (AD), such as neurofibrillary tangles (NFT) and beta-amyloid plaques are 'advanced glycation endproducts' (AGE). Using a polyclonal antibody against AGE in frozen sections of fixed brain tissue from Alzheimer's disease patients, AGE were identified in a further characteristic protein deposit in AD, namely in Hirano bodies. AGE are localized to ovoid, spherical, and rod-like Hirano bodies in the hippocampus, particularly numerous in the stratum lacunosum-moleculare of CA1. Since Hirano bodies are known to contain mainly cytoskeletal and cytoplasmic components and are localized within the soma of neurons our study suggests that AGE formation and intracellular protein crosslinking represent early stages during neuronal degeneration.

Alzheimer Disease↗
PubMed1998

Distribution of advanced glycation end products in the cerebellar neurons of dogs.

Nonenzymatically glycated proteins and their advanced stage, the 'advanced glycation end products' (AGEs), have been detected in long-lived proteins and protein deposits in human and animal tissues. They are thought to be associated with normal aging and particularly with the pathogenesis of diabetic complications and Alzheimer's disease. AGEs accumulate in human neurons in an age-dependent manner and, in Alzheimer's disease patients, particularly in amyloid plaques and neurofibrillary tangles. In this study, we demonstrate AGE immunoreactivity in the canine brain, particularly in cerebellar Purkinje cells and brainstem neurons. In addition, distinct AGE-positive granules can be detected in the Purkinje cells which accumulate in an age-dependent manner. Staining with PAS and oil-red suggests that these AGE-positive granules contain the protein, but not the lipid constituents associated with lipofuscin. Our results show that the pattern of AGE distribution in the canine cerebellum resembles the situation in the human brain, but that the time course of AGE formation is much faster in dogs reflecting their much shorter life span.

Animals↗