Dilated Glomerular Capillaries Research Articles

Effects of Subchronic Exposure to Phosalone on Oxidative Stress and Histopathological Alterations in Common Carp (Cyprinus carpio, L., 1758)

In this study, possible oxidative stress, biomarkers, and histopathological alterations were investigated in common carp (Cyprinus carpio, L., 1758) that were exposed to various phosalone concentrations in vivo. Fish were exposed to 0.15, 0.3, and 0.6 mg/L phosalone concentrations in a semistatic regime for 14 d. Biomarkers, including Na+, K+-ATPase, reduced glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), and histopathological changes, were determined in gills, liver, and kidney tissues of fish. Sublethal phosalone concentrations produced lipid peroxidation and impairment in the antioxidant defense system by increasing reactive oxygen species (ROS) production. While GSH increased in all groups at d 7 compared to control, GSH fell significantly at medium and high doses at d 14. Reduced GSH levels were diminished in all tissues and a significant induction in lipid peroxidation (TBARS) was observed. Na+,K+-ATPase enzyme activity was significantly inhibited especially in gills. No histopathological effects were observed in the control group. Lamellar aneurysm, lamellar fusion, hyperplasia, epithelial lifting, and hemorrhages were observed in gill tissues exposed to phosalone. Histopathological effects in the liver tissues of fish exposed to phosalone were characterized by cytoplasmic vacuolation, congestion, hypertrophy, and nuclear degeneration. Hypertrophy, tubule degeneration, mononuclear cell infiltration, and dilation of glomerular capillaries were noted in kidney tissues exposed to phosalone. The results indicate that phosalone exposure adversely affected the health of the fish, attributable to oxidative stress.

Liver and renal lesions in mercury-contaminated narwhals (Monodon monoceros) from North West Greenland

Narwhals (Monodon monoceros) from North West Greenland are known to bioaccumulate mercury (Hg) in tissues and internal organs. This is postulated to be a health concern and therefore studies were undertaken to conduct a screening study of Hg concentrations and histopathology of liver and renal tissues in a total of 12 specimens. The sample consisted of two sub-adults (one male, one female) and 10 adult (six males, four females) collected in Qaanaaq (Thule) 2010. In liver, Hg mean ± SD was 11.88 ± 10.47 μg/g ww (range: 0.39−31.8 μg/g ww) while the concentrations in kidneys were 1.85 ± 1.20 μg/g ww (range: 0.41−4.03 μg/g ww). There was no marked difference in Hg concentrations between males and females while sub-adults had significantly lower concentrations. The histological examinations of renal tissue showed glomerular capillary dilatation and basement membrane thickening, dilatation, and hyalinization of Bowman's space/capsule and tubular lesions with hyaline casts accompanied by interstitial fibrosis in the kidneys. In liver tissue, portal cell infiltrates and fibrosis, bile duct proliferation, lipid-filled Ito cells, and steatosis were found. There was no marked difference in histological prevalence between males and females and in Hg concentrations in individuals with or without lesions. Four of seven renal lesions and one liver lesion were found in the two sub-adult whales. Based upon these findings, as well as the nature of the lesions, evidence suggests that histopathological alterations were a result of age but that Hg might be an aggravating co-factor in development of renal lesions in particular.

A case of lipoprotein glomerulopathy with thrombotic microangiopathy due to malignant hypertension

BackgroundLipoprotein glomerulopathy (LPG) is a rare inherited renal disease characterized by intraglomerular lipoprotein within the lumina of severely dilated glomerular capillaries. The common clinical presentation of LPG includes proteinuria or nephrotic syndrome. Hypertension and anemia were thought to be mild in LPG. Thrombotic microangiopathy (TMA) in LPG has not been previously reported. In this report, we present a patient with LPG that developed TMA. To the best of our knowledge, this is the first report of TMA in LPG.Case presentationFour years ago (2005), a 19-year-old Chinese woman was diagnosed with nephrotic syndrome and provided prednisone treatment. A combination of prednisone and cyclophosphamide did not have any effect and was discontinued after six months. Although she was steroid-resistant, over the next subsequent three years, she maintained normal renal function without anemia and thrombocytopenia. In February 2009, she had a severe headache and blurry vision and presented at a local hospital with severe hypertension. Blood pressure was 220/160 mmHg. Laboratory data showed hemoglobin 3.8 g/dL; platelet counts 29×109/L; urinary protein 7.90 g/d; total bilirubin 29.9 umol/L; indirect bilirubin 28.2 umol/L; LDH 1172 U/L; ALB 2.66 g/dL; urea nitrogen 52 mg/dL; serum creatinine 3.2 mg/dL; triglyceride 253 mg/dL; total cholesterol 273 mg/dL. ANA, ds-DNA, ANCA, anti-GBM antibody and anticardiolipin were all negative. A renal biopsy revealed LPG with TMA. Genetic evaluation showed the patient carried the APOE Kyoto mutation. Adequate control of blood pressure improved microangiopathic anemia and thrombocytopenia, however, renal function did not improve and she eventually developed uremia and became hemodialysis dependent.ConclusionWe report on a rare case of TMA probably due to malignant hypertension in LPG. Early lipid-lowering and antihypertensive treatment may improve outcome. The pathophysiologic relationship between LPG and TMA should be investigated further.

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy

Obesity, an ongoing significant public health problem, is a part of complex disease characterized as metabolic syndrome. Medaka and zebrafish are useful aquatic experimental animals widely used in the field of toxicology and environmental health sciences and as a human disease models. In medaka, simple feeding of a high fat diet (HFD) can induce body weight gain, excessive accumulation of visceral adipose tissue, hyperglycemia, hyperlipidemia, and steatohepatitis, which mimics human metabolic syndrome. In the present study, to explore the possibility that the adult medaka fed with HFD (HFD-medaka) can be used as an animal model for human metabolic syndrome-associated glomerular disease, including obesity-related glomerulopathy (ORG), we analyzed structural alterations and protein expression in the mesonephric kidney of HFD-medaka. We found that the histopathology was consistent with glomerulomegaly accompanied by the dilation of glomerular capillaries and proliferative expansion of the mesangium, a condition partially comparable to human ORG. Moreover, expressions of several kinds of kidney disease-related proteins (such as MYH9, SM22α) were significantly elevated. Thus, the HFD-medaka has a high potential as an animal model useful for exploring the mechanism underling human ORG.

Histopathological alterations in gill, liver and kidney of common carp exposed to chlorpyrifos

Histopathological alterations in gill, liver and kidney of common carp, Cyprinus carpio, intoxicated with sub-lethal concentrations of chlorpyrifos (O,O,-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate) pesticide (1 and 100 μg/L) for a period of 14 days were analyzed under light microscope. Gill exhibited hyperplasia and hypertrophy of gill epithelium, blood congestion, dilation of marginal channel, epithelial lifting, lamellar fusion, lamellar disorganization, lamellar aneurysm, rupture of the lamellar epithelium, rupture of pillar cells and necrosis. Alterations in hepatocytes were more pronounced, including nuclear and cellular hypertrophy, cellular atrophy, irregular contour of cells and nucleus, cytoplasmic vacuolation, cytoplasmic and nuclear degeneration, cellular rupture, pyknotic nucleus, necrosis and melanomacrophages aggregations. Histopathological lesions in kidney were cellular and nuclear hypertrophy, narrowing of tubular lumen, cytoplasmic vacuolation, hyaline droplet degeneration, nuclear degeneration, occlusion of tubular lumen, tubular regeneration, dilation of glomerular capillaries, degeneration of glomerulus and hemorrhage in Bowman's space. The most significant conclusion drawn from this study was that with the increased concentration and duration the toxicosis of chlorpyrifos would be enhanced as shown through the analysis of mean assessment value (MAV) and degree of tissue changes (DTC) also.

A Novel Apolipoprotein E Mutation, ApoE Osaka (Arg158 Pro), in a Dyslipidemic Patient with Lipoprotein Glomerulopathy

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by the presence of thrombuslike deposition in markedly dilated glomerular capillaries and is often accompanied by an increased serum apolipoprotein E (apoE) level. Several gene mutations of apoE have been reported to be associated with LPG. In the current study, we report an LPG patient with a novel apoE mutation, apoE Osaka. The patient was a 45-year-old man who was hospitalized due to nephrotic syndrome. Light and electron microscopic observations of renal biopsy clearly showed characteristic findings of LPG, including lamellate thrombi in the lumen of dilated glomerular capillaries. His apoE phenotype was apoE3/2 and he had mild dyslipidemia with a mid-band on polyacrylamide gel electrophoresis. It is intriguing that the serum apoE level was within normal limits. We determined the sequence of the apoE gene using direct sequencing of the polymerase chain reaction (PCR) products. ApoE gene analysis showed a nucleotide substitution of G to C at codon 158 of exon 4. This mutation denoted an amino acid substitution of arginine residue for the proline residue at position 158 of apoE. The result of PCR associated with restriction fragment length polymorphism analysis also suggested that this mutation is heterozygous. It is possible that apoE Osaka mutation causes a conformational change of apoE protein and affects the interaction between abnormal apoE-containing lipoproteins and the endothelial cells of glomerular capillaries. The precise mechanism of LPG related with apoE Osaka, however, remains to be elucidated.

A new apolipoprotein E mutation, apoE Las Vegas, in a European-American with lipoprotein glomerulopathy

Lipoprotein glomerulopathy is a rare disease diagnosed by unique histopathologic findings of glomerular capillary dilatation by lipoprotein thrombi. The disease is caused by mutations in apoE, the gene that encodes apolipoprotein E. To date, <80 cases have been reported in the medical literature, nearly all of which are from Japan or China. Only five cases from the United States have previously been reported, of which three patients were of European ancestry. Here, we present the fourth case of lipoprotein glomerulopathy in a European-American man. Whereas prior European-American patients with lipoprotein glomerulopathy were found to have the previously reported apoE Kyoto genotype, the patient presented here was found to have a novel mutation that we have named apoE Las Vegas.

Liver and renal histopathology of North Atlantic long-finned pilot whales (Globicephala melas) contaminated with heavy metals and organochlorine compounds

Long-finned pilot whales (Globicephala melas) from the Faroe Islands are known to be heavily polluted with contaminants, such as mercury (Hg) and organochlorine compounds (OC). This is postulated to exert adverse health effects on whales as well as the human population who rely on its meat and blubber as food sources. It was therefore decided to conduct a screening pilot study to determine contaminant concentrations and histopathology of liver and renal tissues in a total of 14 specimens from this subpopulation. In blubber, the mean ∑OC concentration was 31,887 ng g−1 lw (range: 18,170–47,425 ng g−1 lw) of which ∑PCB concentration was 23,416 ng g−1 lw (range: 13,947–34,543 ng g−1 lw; n = 3). In liver, mean Hg concentration was 138 µg−1 ww (range: 54–351 µg g−1 ww; n = 7) and mean cadmium (Cd) concentration 15 µg g−1 ww (range: 7–31 µg g−1 ww; n = 7). In the kidney, the mean Cd concentration was 36 µg g−1 ww (range: 23–47 µg g−1 ww; n = 7). Of the liver Hg concentrations, two were at the suggested toxic threshold levels of 60 µg g−1 ww and five were 2–6-fold above. Liver selenium (Se) : Hg was on average 1.11 (range: 0.97–1.41; n = 7) indicating that Se was in excess, which decreased the risk of acute Hg poisoning. Histopathological examinations showed high prevalence (>35%) of renal glomerular arteriosclerosis, glomerular capillary dilatation, dilatation and hyalinization of Bowman's space/capsule and tubular hyaline casts. In liver tissue, high prevalence was found for portal cell infiltrates, lipid granulomas, hepatocytic lipid accumulation, bile duct proliferation, lipid-filled Ito cells, and focal necrosis. In a single juvenile male, 4 of 8 renal and 3 of 7 liver lesions were present. Cadmium concentrations increased significantly in the presence of glomerular arteriosclerosis and a similar trend was found for tubular hyaline casts. Based on these findings, as well as the nature of the lesions, data indicate that the histopathological changes were a result of age and that contaminants are likely to be the co-factors in the development in at least three renal and four liver lesions.

Histological and Ultrastructural studies on the kidneys of albino rat under the effect of tiaprofenic acid and the possibility of recovery after stoppage of the drug

ABSTRAT The present study was performed to evaluated the pathological effect s of tiaprofenic acid (surgam) on the kidneys of adult male albino rat and the possibility of recovery after stoppage of the drug administration. 40 male albino rats divided into 4 equal groups were used in this study. Group I: (the control group) the animals were intramuscularly injected with 0.5 ml physiological saline solution. Group II, the animals were intramuscularly injected with the therapeutic dose of tiaprofenic acid (TA) (18 mg/kg b.w.) every 12 hours for 2 weeks. Group III, the animals were intramuscularly injected with double the therapeutic dose of (TA) (36 mg/kg b.w.) every 12 hours for 2 weeks. Group IV, the animals were intramuscularly injected with double the therapeutic dose of (TA) (36 mg/kg b.w.) every 12 hours for 2 weeks and then left without trea tment for 4 weeks for the possibility of recovery. Animals of groups I,II,III were sacrificed 24 hours after the last dose, while animals of group IV were sacrificed 4 weeks after the last dose, and the kidney samples were obtained and processed for histological and ultrastructural examination s. Histological changes in the rat kidney induced by tiaprofenic acid (TA) included hypertrophied glomeruli, swelling of the parietal epithelial cells, proliferation of the mesangial cells, and narrowing of the urinary spaces. Moreover, the cells of the proximal and distal convoluted tubules showed marked cloudy swelling with hypertrophied nuclei ; some displayed signs of pyknosis and karyolysis. Many infla mmatory cells invading the intertubular spaces were also seen.Ultrastructural observations revealed sw ollen of the parietal epithelial cells of Bo wman’s capsules , narrow urinary spaces, focal fusion of the visceral epithelial cells, thickened glomerular basement membrane and dilated glomerular capillaries with the prescence of amorphous materials as well as blood cells in the capillaries lumina. The proximal convoluted tubules showed erosion of the microvilli constituting the brush borders, with cell debris or cast in the lumina of the tubules; besides, degenerated mitochondria and lysosomes, fragmented rough endoplasmic reticulum and destruction of the basal infolding s were observed. The epithelial cells of the distal convoluted tubules manifested marked loss of some basal infoldings as well as degenerated mitochondria, and destructed endoplasmic reticulum. However, in the recovery group there was marked improvment in the kidney tissues which appeared more or less normal.

Nephrotic Syndrome Induced by Dibasic Sodium Phosphate Injections for Twenty-eight Days in Rats

Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

Identification of Apolipoprotein E Guangzhou (Arginine 150 Proline), a New Variant Associated with Lipoprotein Glomerulopathy

Background/Aims: Lipoprotein glomerulopathy (LPG) is a rare disease characterized by thrombus-like substances in markedly dilated glomerular capillaries and elevated plasma levels of apolipoprotein E (apoE). Previous studies have shown that genetic disorders of apoE may contribute to the pathogenesis of LPG, but LPG may not be caused by apoE gene mutations in Chinese patients. This study investigated the association of a new variant of apoE with LPG in a Chinese family. Methods: The apoE gene in a family with 4 LPG patients was sequenced. The polymerase chain reaction product of coding region of apoE exon 4 was cloned into pMD 18-T vector and then sequenced. Results: A novel point mutation in exon 4 of the apoE gene was identified in all 4 LPG patients and 1 asymptomatic family member. Sequence analysis confirmed a nucleotide G to C point mutation in exon 4 (base 308) of the apoE gene in all patients and the asymptomatic family member. This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 150 of apoE. Those patients were all heterozygotes with apoE Guangzhou. One of 2 grandsons was a heterozygous carrier of apoE Guangzhou, although he did not have proteinuria. Conclusion: The results of this study suggest that apoE (arginine 150 proline) is a novel apoE variant that etiologically related to LPG. This variant (apoE Guangzhou) may cause a marked molecular conformational change of the apoE and thus impair its binding ability to lipids.

The role of the type I insulin-like growth factor receptor (IGF-IR) in glomerular integrity

Insulin-like growth factors (IGFs) have been implicated in normal mammalian kidney development. To confirm a role for the IGF system in podocyte and glomerular integrity, we generated a transgenic mouse that expresses a dominant-negative type 1 IGF receptor (IGF-IR) and determined the structural and functional consequences. Using a 4.25 kb fragment of the murine nephrin promoter, the dominant-negative construct was expressed exclusively in the kidney, confirmed by Southern blot and RT-PCR analysis. IGF-Ir486 FLAGstop protein localized specifically to the glomerular podocyte based on FLAG immunohistochemistry and on co-localization with nephrin and podocin. Wild type and transgenic glomeruli expressed both the α- and β-subunits of the endogenous IGF-IR, with normal expression of both nephrin and podocin. Although the animals were viable and phenotypically normal, histological analysis of the kidneys revealed abnormal and small glomeruli with dilated glomerular capillaries and condensed podocyte nuclei, while ultra-structural examination revealed diffuse but segmental podocyte foot process broadening, fusion, and effacement. Explanted glomeruli from transgenic animals demonstrated a significant inhibition of podocyte cell outgrowth when compared to controls. These studies suggest that IGF signaling is essential for maintaining the integrity of the podocyte and that alterations of IGF signaling may play a role in progressive glomerular disease.

Structural Alterations of the Glomerular Wall and Vessels in Early Stages of Diabetes Mellitus (Light and Transmission Electron Microscopic Study)

Objective: The capillary changes at the initial stage of diabetes may show an angioarchitecture clearly different from those of later stages and/or very severe glomerular change. However, the onset of alterations in the early phases is unclear. This study attempts to determine the structural alterations of the glomerular wall and vessels in the early stage of diabetes. Material and Methods: Twenty-five adult rats were used in this study. They were divided into two groups: the first group of five was used as a control .The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, two months, and four months. Five rats at two months of age with hyperglycemia were treated with insulin for eight weeks. Renal tissues were prepared by routine technique for light and transmission electron microscopic evaluation. Results: By light microscopy after ten days of induced hyperglycemia, there were no structural modifications detected either in renal glomerular fine vessels or in the glomerular basement membrane of the glomerular capillaries. After two months, there was a moderate glomerular enlargement and dilatation of glomerular capillaries, afferent, and efferent arterioles. After four months, glomerular basement membrane thickening was the only structural alteration observed. Recovery of the glomerular alterations was observed after two months of treatment with insulin. Conclusion: In early stages of diabetes mellitus in rats, there was an increase in the diameter of glomerular vessels. In later stages of the disease, the reverse was seen, but insulin treatment had a positive role in reversing these changes in the study subjects.

Structural alterations of the glomerular wall and vessels in early stages of diabetes mellitus: (light and transmission electron microscopic study).

ObjectiveThe capillary changes at the initial stage of diabetes may show an angioarchitecture clearly different from those of later stages and/or very severe glomerular change. However, the onset of alterations in the early phases is unclear. This study attempts to determine the structural alterations of the glomerular wall and vessels in the early stage of diabetes.Material and MethodsTwenty-five adult rats were used in this study. They were divided into two groups: the first group of five was used as a control. The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, two months, and four months. Five rats at two months of age with hyperglycemia were treated with insulin for eight weeks. Renal tissues were prepared by routine technique for light and transmission electron microscopic evaluation.ResultsBy light microscopy after ten days of induced hyperglycemia, there were no structural modifications detected either in renal glomerular fine vessels or in the glomerular basement membrane of the glomerular capillaries. After two months, there was a moderate glomerular enlargement and dilatation of glomerular capillaries, afferent, and efferent arterioles. After four months, glomerular basement membrane thickening was the only structural alteration observed. Recovery of the glomerular alterations was observed after two months of treatment with insulin.ConclusionIn early stages of diabetes mellitus in rats, there was an increase in the diameter of glomerular vessels. In later stages of the disease, the reverse was seen, but insulin treatment had a positive role in reversing these changes in the study subjects.

Gill and kidney histopathology in the freshwater fish Cyprinus carpio after acute exposure to deltamethrin

The histopathological effects of deltamethrin on the gill and kidney tissues of the common carp, Cyprinus carpio were determined by light microscopy. The fish were exposed to 0.029 mg l −1 (50% of 96 h LC 50) and 0.041 mg l −1 (70% of 96 h LC 50) solutions of deltamethrin for short-term (96 h). The most common gill changes at all doses of deltamethrin were desquamation and necrosis. Besides, aneurism in secondary lamellae, lifting of the lamellar epithelium, oedema, epithelial hyperplasia and fusion of the secondary lamellae were reported. Lesions in the kidney tissues of fish exposed to deltamethrin were characterized by degeneration in the epithelial cells of renal tubule, pycnotic nuclei in the hematopoietic tissue, dilation of glomerular capillaries, degeneration of glomerulus, intracytoplasmatic vacuoles in epithelial cells of renal tubules with hypertrophied cells and narrowing of the tubular lumen.

Glomerular changes in BK virus nephropathy

This study seeks to define the glomerular changes that are associated with human BK virus nephropathy (BKVN). It is based on histopathologic review of 124 biopsies showing light-microscopic changes of viral nephropathy. The diagnosis of BKVN was confirmed by immunohistochemistry or by in situ hybridization. Histological lesions were scored by the Banff 97 criteria for renal allograft pathology and were correlated with clinical parameters. Viral cytopathic effect in the parietal Bowman’s capsular epithelium was seen in 21/124 (17%) biopsies. Immunohistochemistry showed infection of Bowman’s capsular epithelium in an additional 15/124 (12%) biopsies. Crescents were found in 15/124 (12%) samples. Glomerulitis exceeding grade Banff g1 was only occasionally shown (4/124 = 3% biopsies). Other pathologic lesions documented include mild increase in mesangial matrix in 23% biopsies, aneurysmal dilatation of glomerular capillaries in 28%, ischemic glomerulopathy in 62%, and chronic transplant glomerulopathy graded as mild (cg1) in 62% of biopsies and as moderate (cg2) in 2/124 (1.9%) biopsies. These findings show that infection of the glomerular epithelium cells can occur in a subset of patients with BKVN, most often in biopsies with high viral load in the tubular epithelium. Isolated crescents can occur in BKVN biopsies, but rapidly progressive glomerulonephritis is not observed. Two biopsies showed electron-dense deposits on ultrastructural examination, but a cause and effect relationship to BK virus infection could not be established.

The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats

Since adrenomedullin (AM) elicits vasodilatation by binding to specific AM receptors consisted of calcitonin-receptor-like receptor (CRLR)/receptor-activity-modifying protein 2 (RAMP2) or CRLR/receptor-activity-modifying protein 3 (RAMP3) on endothelial cells and stimulating nitric oxide production, AM possibly involves in glomerular capillary dilatation in early phase of diabetic nephropathy. Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats at 4 weeks after the injection were employed for expression studies of AM, RAPM2, and RAMP3. The measurement of AM peptide levels in kidney tissue, plasma, and urine was performed. Human aortic endothelial cells (HAEC) were used to investigate functional link between glucose-induced AM production and nitric oxide release. STZ rats showed glomerular hypertrophy and increased urinary NO2- and NO3- excretion. By Northern blot analyses, AM and RAPM2 mRNAs significantly increased in the kidneys of STZ rats, while RAMP3 mRNA was not altered. In STZ rats, AM peptide was actively secreted into urine (1280 +/- 360 fmol/day vs. control 110 +/- 36 fmol/day). AM peptide was mainly detected on cortical and medullary collecting duct cells in control rat kidneys and AM peptide and mRNA were up-regulated on afferent arterioles and glomeruli of STZ rats. RAMP2 expression was detected on afferent arterioles and not in glomeruli in control rats and it was up-regulated on glomerular endothelial cells in STZ rats. In HAEC culture, d-glucose stimulated AM and nitric oxide production and they were suppressed by addition of AM antisense oligodeoxynucleotides. Up-regulated expression of AM and RAMP2 in afferent arterioles and glomeruli may be related to selective dilatation of glomerular capillary in acute phase of type 1 diabetes.

Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.

Chronic Graft-versus-Host Autoimmune Disease in Fc Receptor γ chain-deficient Mice Results in Lipoprotein Glomerulopathy

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.

Histopathology of feral fish from a PCB-contaminated freshwater lake.

The purpose of this study was to evaluate the potential toxic effects of chronic sublethal polychlorinated biphenyl (PCB) exposure on feral fish, using histopathology as an endpoint. Histopathological study of bream (Abramis brama) and asp (Aspius aspius) living in a PCB-polluted freshwater lake revealed abnormal cellular changes in the renal corpuscle of both species. Dilation of glomerular capillaries (DGC), mesangial edema (ME), an adhesion between visceral and parietal layers of Bowman's capsule (ABC), and filling of Bowman's space (FBS), were highly prevalent features in lake fish. The prevalence of each of these lesions was significantly lower, or totally absent in fish caught from reference locations. Cellular alterations in liver, gill, gonads, spleen, and intestine were all linked to seasonal changes. The results suggest that some of the observed histopathological changes in renal glomeruli, particularly DGC and ME, could possibly indicate a prolonged chemical stress caused by PCBs and related compounds. It is also possible that chronic PCB exposure may have suppressed and weakened the immuno systems of exposed fish making them more vulnerable to secondary parasitic infections.