Dilated Glomerular Capillaries Research Articles

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation

BackgroundThis article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature.Case presentationThe young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient’s mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient’s urinary protein was partially controlled, and the albumin level was recovered.ConclusionPatients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient’s symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.

In the present study, we aimed to explore the effect and underlying mechanism of metformin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). A total of 24 BALB/C mice were randomly divided into four groups: control group, LPS group and metformin group (50 or 100mg/kg). The histological changes and cell apoptosis in kidney tissues were detected by hematoxylin-eosin staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling assay, respectively. Enzyme-linked immunosorbent assay was applied to determine serum levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), creatinine (Cre), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Western blotting analysis were carried out to confirm the expressions of monocyte chemotactic protein-inducible protein 1 (MCPIP1), silent information regulator sirtuin 1 (SIRT1), and NF-κB p65 (acetyl K310). Compared with the control group, the mice in LPS group had glomerular capillary dilatation, renal interstitial edema, tubular cell damage and apoptosis. The serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1β in LPS group were significantly higher than those in control group. Moreover, LPS also elevated the expressions of MCPIP1 and NF-κB p65 (acetyl K310) but decreased the expression of SIRT1 in kidney tissues. However, metformin distinctly decreased LPS-induced renal dysfunction, the serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1β. In addition, metformin markedly increased the expressions of MCPIP1 and SIRT1 but decreased the expression of NF-κB p65 (acetyl K310) in kidney tissues. Metformin prevented LPS-induced AKI by up-regulating the MCPIP1/SIRT1 signaling pathway and subsequently inhibiting NF-κB-mediated inflammation response.

Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway

To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1β (P < 0.01), enhanced renal expressions of TNF-α, IL-1β and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1β (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.

Screening for polystyrene nanoparticle toxicity on kidneys of adult male albino rats using histopathological, biochemical, and molecular examination results

Polystyrene Nanoparticles (PS-NPs) used for packaging foam, disposable cups, and food containers. Therefore, this study aimed to evaluate PS- NPs toxic effects on kidney of adult male albino rats. A total of 30 rats divided into three groups (n = 10): group I negative control group; group II orally administered 3% PS-NPs (3 mg/kg body weight/day) and group III orally administered 3% PS-NPs (10 mg/kg body weight/day) for 35 days. Blood and kidney samples collected and processed for biochemical, histopathological, and immunohistochemical examinations. Results showed that low and high doses PS-NPs had significantly increased serum blood urea nitrogen (BUN), creatinine, malondialdehyde, significantly further reduced glutathione, downregulation of nuclear factor erythroid 2–related factor 2 and glutathione peroxidase, upregulation of caspase-3 and Cytochrome-c. Histopathological examination revealed several alterations. Low dose of PS-NPs exhibited dilated glomerular capillaries, hypotrophy of some renal corpuscles significantly decreases their diameter to 62 μm. Some proximal convoluted tubules and distal convoluted tubules showed loss of cellular architecture with pyknotic nuclei. Hyalinization and vacuolation in renal medulla. In high dose PS-NPs, alterations increased in severity. A significant increase in percentage area of cyclooxygenase-2 in low and high-doses. In conclusion, PS-NPs are a nephrotoxic causing renal dysfunction.

Kidney Histopathology Features of Suspected Intra-Kidney Venous Thromboembolism in Patients with Primary Glomerulonephritis

Introduction: Renal vein thromboembolism is a severe complication of nephrotic syndrome. Small thrombus in the intra-kidney venous system cannot be recognized by ultrasonography. The current study was to investigate the kidney pathological features of intra-kidney venous thrombus and their values in clinical practice. Methods: Kidney pathological features of glomerular capillary dilatation and congestion, peritubular capillary dilatation and congestion, and intraglomerular neutrophil infiltration were screened and scored during kidney biopsy information interpretation. Eighty-four consecutive patients with these features and primary glomerulonephritis were analyzed, comparing to another 84 control patients without these features who were matched according to the pathological types of glomerulonephritis. Results: In the patients with pathological features of suspected intra-kidney venous thrombus, the levels of proteinuria (5.2 vs. 3.2 g/24 h, p = 0.005), serum creatinine (80.9 vs. 71.2 μmol/L, p < 0.001), platelet count (274.0 vs. 254.5 ×10⁹/L, p = 0.020), D-dimer (0.2 vs. 0.2 mg/L, p = 0.002), and fibrin degradation products (1.9 vs. 1.0 mg/L, p = 0.003) were significantly higher than those in control patients. The levels of serum albumin (24.2 vs. 28.6 g/L, p = 0.003) and eGFR (92.1 vs. 103.9 mL/min/1.73 m², p < 0.001) were significantly lower. The scores of these pathological features were positively correlated with the levels of D-dimer (r = 0.21, p = 0.05). During follow-up, 9 (10.7%) patients with pathological features of suspected intra-kidney venous thrombus developed venous thromboembolism, which was significantly more than that of control patients (0%, p = 0.006). Conclusions: Kidney pathological features could indicate intra-kidney venous thromboembolism, and their scores represent the possibility of thrombus. The notice of these features may provide clinical alerts for venous thromboembolism possibility.

VEGF-VEGFR2 inhibitor-associated hyaline occlusive glomerular microangiopathy: a Japanese single-center experience.

Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients. We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients. All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients. Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.

Bacopa Monnieri Protects the Directly Affected Organ as Well as Distant Organs Against I/R Injury by Modulating Anti-Inflammatory and Anti-Nitrosative Pathways in A Rat Model for Infra-Renal Aortic Occlusion

Objective To investigate the protective effect and underlying mechanisms of B. monnieri, a medicinal plant, on kidney and skeletal muscle injury induced by infra-renal abdominal aorta clamping for 2-hours (ischemia) and following removal of the clamp (reperfusion, 2-hours). Methods Rats were divided into four groups (n = 6): (I) animals given only saline (sham-control); (II) animals given B. monnieri extract for 10-days (300 mg/kg/day) (Bacopa-treated sham); (III) animals subjected to ischemia/reperfusion (I/R); (IV) animals given B. monnieri extract and then subjected to I/R. Kidneys and lower extremity muscles were examined for GPx, CAT, iNOS, 3-NT, IL-1β and TNF-α. Apoptosis and injury were evaluated by TUNEL and H&E staining, respectively. Results I/R resulted in TUNEL positive cells, periarterial edema and glomerular capillary dilatation, decreased GPx activity, unchanged CAT, iNOS, 3-NT, IL-1β and TNF-α in kidney. B. monnieri minimized renal remote reperfusion injury, and Group IV showed a lower degree of renal histopathology score when compared to the others. B. monnieri mitigated muscle I/R injury, decreased muscle hypertrophy, myofibril abnormalities and apoptosis. Muscle 3-NT and cytokine levels were increased by I/R, and B. monnieri inhibited iNOS and 3-NT both in sham-control and I/R groups. Muscle GPx unaffected by I/R or B. monnieri, but CAT was inhibited only in B. monnieri-treated I/R group. Muscle iNOS, 3-NT, IL-1β, TNF-α levels and CAT activity of B. monnieri-treated I/R rats were lower than those in sham-control or Bacopa-treated sham. Conclusions B. monnieri can protect the directly affected organ as well as distant organs against I/R injury by modulating anti-inflammatory and anti-nitrosative pathways.

Hematologic, biochemical, genetic, and histological biomarkers for the evaluation of the toxic effects of fipronil for Rhamdia quelen

This study aimed to determine the lethal concentration 50% (LC$_{50}$) and behavioral, hematological, biochemical, histopathological, and genetic disorders of fipronil for Rhamdia quelen in acute toxicity tests for 96 h. To determine the LC$_{50}$, 42 juveniles were distributed in groups of 0, 0.1, 0.2, 0.3, 0.4, 0.5, and 0.8 mg L$^{-1}$ of fipronil. For other evaluations 36 silver catfish were divided into control, 0.3 mg L$^{-1}$, and 0.4 mg L$^{-1}$ groups. Blood, kidneys, livers, and gills were collected for evaluation. The LC$_{50}$ calculated with probit-type regression was 0.811 mg L$^{-1}$ at 48 h of study. There was total mortality of 0.8 mg L$^{-1}$, reduction in hematocrit values, and increase in liver enzymes. Liver samples showed cytoplasmic vacuolization and cellular degeneration, among other changes. Gills presented vascular congestion, complete fusion of secondary lamellae, and epithelial cell hypertrophy. In the kidneys, changes such as Bowman?s capsule clearance, tubular degeneration, and glomerular capillary dilatation, among others, were common. Erythrocytes showed morphological alterations without increased micronucleus development. Fipronil induces a clinical condition of anemia, alterations in liver enzyme levels, nuclear erythrocyte changes, and liver, gill and kidney damage in the silver catfish.

Environmentally induced nephrotoxicity and histopathological alternations in Wallago attu and Cirrhinus mrigla.

Fish kidneys are sensitive to chemical changes in the freshwater ecosystem because they are directly and constantly exposed to chemicals dissolved in the water. This study evaluated nephrotoxicity in Wallago attu and Cirrhinus mrigala harvested from the Chenab River in an area of industrial and sewage waste disposal. Induced histological alternation data were correlated to the severity of environmental degradation in order to determine whether this biological system can be used as a tool for environmental monitoring programs. Kidneys from two fish species occupying different niches were collected and stored for 24 h in 10% formalin. Control fish were collected upstream of the polluted river area. Specimens were processed using topical histological methods. The major histological alterations observed in both species were renal tubule myxospora, hyperemia, glomerulonephritis, degeneration of renal tubule cells, dilation of glomerular capillaries, presence of pycnotic nuclei in the hematopoietic tissue, epithelial hypertrophy, vacuolization, reduced lumen of renal tubules, and shrinkage of glomeruli. Renal tubular atrophy, degeneration due to extensive degranulation, necrosis of glomeruli, glomerular expansion, absence of Bowman’s space, hypertrophied nucleus, necrosis and hyalinization of the interstitium, clogging of tubules, and regeneration of tubules was also observed. Wallago attu exhibited the maximum incidence of moderate to severe changes and was defined as having the highest “histopathologic alteration index”. These severe alterations were found to be related to environmental degradation, indicating the presence of stressors in freshwater. Control groups showed normal tissue morphology in the kidneys.

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function.

Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM‐1, CTSL by qRT‐PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM‐1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM‐1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker.

Hepatic and renal histology and mercury concentrations of North West and North East Greenland narwhals (Monodon monoceros)

ABSTRACTNarwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males). The zoological length was significantly larger and hepatic and renal concentrations significantly higher in adults compared to subadults. When comparing tissues, the Hg levels were significantly the highest in liver, while a correlation between metal levels in liver and kidneys was positive and significant. Histological examination of renal tissues presented four types of glomerular lesions (capillary dilatation [0–100%], membrane thickening [0–100%], dilatation of space [0–80%], and sclerosis [0–70%]) and two tubular lesions (atrophy/hyalinization [0–40%] and casts [0–60%]). Hepatic tissues exhibited three portal lesions (fibrosis [0–33%], cell infiltrates [0–40%], and bile duct proliferation [0–40%]) and two parenchymal lesions (steatosis [83–100%] and lipid-filled Ito cells [0–33%]). All 12 lesions were found in adult whales from North West Greenland while eight were present in adult whales from North East Greenland. Six lesions were detected in subadults from North East Greenland and four in subadults from North West Greenland. A significantly higher frequency of dilatation and hyalinization of Bowman’s space and capsule and glomerular capillary dilatation was found in adult narwhals from West Greenland. There was no marked difference in Hg concentrations in whales with and without histological lesions. In conclusion, the prevalence of histological changes and Hg levels were the highest in adults and therefore both age and metal are important factors to include when evaluating liver and kidney lesions in narwhals.

A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I.

Lipoprotein glomerulopathy (LPG) is a rare inherited disease characterized by histopathological features of lipoprotein thrombi in dilated glomerular capillaries and type III like hyperlipoproteinemia with heterozygous mutation of the apolipoprotein (apo) E gene. We herein present the case of a 50-year-old woman with LPG complicated by neurofibromatosis type 1 (NF1). To the best of our knowledge, this is the first report of a case of LPG complicated by NF1. On the other hand, she had not only a heterozygous apoE-Sendai mutation, which is one of the most frequent apoE variants in LPG patients, but also a rare isoform of ApoE5 (Glu3Lys). Although apoE mutation has been recognized as having a principal role in the pathogenesis of LPG, some other factors are assumed to be present in the pathogenesis of LPG, because many asymptomatic carriers of apoE variants are recognized. The coexistence of NF1 or apoE5 (Glu3Lys) allele might play a role as an additional factor in the development of LPG.

Histological and Immunohistochemical Study of Titanium Dioxide Nanoparticle Effect on the Rat Renal Cortex and the Possible Protective Role of Lycopene

Introduction: Titanium dioxide nanoparticles (TNPs) have a wide range of applications in industry, medicine and environmental technology. Nowadays, TNPs have raised researcher’s concerns on their toxicity. Lycopene is a dietary carotenoid having a potent antioxidant effect.Aim: To evaluate the effect of TNPs on the structure of renal cortex of rats and to assess the possible protective effect of lycopene against TNPs nephrotoxicity.Material and methods: Forty five adult male rats were divided into four groups. Group I (the control group) included 20 rats, which were divided equally into 4 subgroups. Subgroup IA was the negative control, Subgroup IB given one ml corn oil by gastric tube, Subgroup IC given one ml distilled water intraperitoneally (i.p) and Subgroup ID given one ml corn oil by gastric tube and one ml distilled water (i.p). Group II included 5 rats received a daily dose of 10 mg/kg body weight (BW) of lycopene by gastric tube for 4 weeks. Group III included 10 rats injected with 150 mg/kg BW (i.p.) of TNPs daily for 4 weeks. Group IV included 10 rats received both TNPs and lycopene at the same aforementioned doses for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin and Masson’s trichrome. Immunohistochemical detection of desmin, anti-proliferating cell nuclear antigen (PCNA) and caspase-3 was done.Results: Our results revealed that group II had similar findings nearly as group I. Group III showed congested dilated glomerular capillaries. The convoluted tubules showed exfoliation of some lining epithelial cells and degenerative changes. There were interstitial haemorrhage, mononuclear cell infiltration and increase in collagen fibers around degenerated convoluted tubules and glomeruli. A significant increase in desmin-expression in the glomerular cells was observed. Besides, there were significant increases of PCNA positive nuclear and caspase-3 cytoplasmic reactions in renal tubular cells. Group IV revealed amelioration of these changes.Conclusion: Lycopene protected rat’s renal cortex against TNPs nephrotoxicity.

Induction of histopathological lesions in renal tissue of the fish Labeo rohita upon exposure to municipal wastewater of Tung Dhab Drain, Amritsar, India

Labeo rohita were subjected to chronic (15, 30, and 60 days) and recovery (60 days) experiments for kidney histopathology studies using sublethal concentrations (35.4%, 26.6%, and 17.7%) of municipal wastewater collected from Tung Dhab Drain, Amritsar, India. Control fish were maintained simultaneously using laboratory tap water, and exhibited normal structures. The results exhibited both dose- and duration-dependent alterations in exposed tissues. The mean degree of tissue change (DTC) values in treated groups ranged from 37.5 ± 6.60 (17.7%, 15 days) to 149.33 ± 7.75 (35.4%, 60 days), demonstrating reparable to irreparable structural changes. The recorded observations showed changes in tubules that included nuclear and cellular hypertrophy, cytoplasmic vacuolation, narrowing of the tubular lumen (stage I), hyaline droplet degeneration, occlusion of the tubular lumen (stage II), and tubular necrosis (stage III). Clear damage was also witnessed in corpuscles that included enlargement of glomerulus, dilatation of glomerular capillaries (stage I), and reduction of Bowman's space (stage II). The recovery experiments showed statistically significant improvement, as the intensity of damage was less than that recorded after 60 days of treatment. The present study indicates toxicity of drain water at the cellular and organ levels, and recommends the use of kidney histopathology as an analytical tool in toxicology and water surveillance studies.

Application of biomarkers in Epaulet grouper (Epinephelus stoliczkae) to assess chromium pollution in the Chabahar Bay and Gulf of Oman

In the present study plasma levels of erythropoietin (EPO) hormone and kidney histological changes were assessed as biomarkers to evaluate the chromium pollution in Epaulet grouper (Epinephelus stoliczkae) obtained from different areas in Chabahar Bay and Gulf of Oman. Chemical analyses included the evaluation of chromium in the fish kidney tissue and sediment. The highest and lowest concentrations of chromium were measured in the kidney of fish and sediment collected from Konarak (47.53±1.23 and 110±1.4μg g–1) and the mouth of Chabahar Bay (3.43±1.31 and 13.5±3.23μg g–1), respectively. There was significant difference (P<0.05) of EPO plasma levels between Konarak, Beris and Ramin stations with the mouth of Chabahar Bay as the cleanest station. Reduction of Bowman's space, occlusion of the tubule lumen, leukocytes infiltration, melanomacrophage centers aggregation, nuclear vacuolation, nuclei hypertrophy of tubule cells, necrosis of the tubules, lifting of the tubular basement membrane and dilatation of glomerular capillaries were the most alterations observed in the kidney. The HAI values of Epaulet grouper from Konarak, Beris and Ramin stations were significantly higher than other stations (P<0.05). It was concluded that selected biomarkers as a first investigation could be useful tools to environmental biomonitoring programs.

Topical nitrogen mustard exposure causes systemic toxic effects in mice

Vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) are reported to be easily absorbed by skin upon exposure causing severe cutaneous injury and blistering. Our studies show that topical exposure of NM (3.2mg) onto SKH-1 hairless mouse skin, not only caused skin injury, but also led to significant body weight loss and 40–80% mortality (120h post-exposure), suggesting its systemic effects. Accordingly, further studies herein show that NM exposure initiated an increase in circulating white blood cells by 24h (neutrophils, eosinophils and basophils) and thereafter a decrease (neutrophils, lymphocytes and monocytes). NM exposure also reduced both white and red pulp areas of the spleen. In the small intestine, NM exposure caused loss of membrane integrity of the surface epithelium, abnormal structure of glands and degeneration of villi. NM exposure also resulted in the dilation of glomerular capillaries of kidneys, and an increase in blood urea nitrogen/creatinine ratio. Our results here with NM are consistent with earlier reports that exposure to higher SM levels can cause damage to the hematopoietic system, and kidney, spleen and gastrointestinal tract toxicity. These outcomes will add to our understanding of the toxic effects of topical vesicant exposure, which might be helpful towards developing effective countermeasures against injuries from acute topical exposures.

Histopathological alterations of mercuric chloride toxicity in marine fish (Acanthopagrus latus)

The present study was conducted to understand the mechanisms of mercury toxicity in marine yellowfin seabream, Achanthopagrus latus fish. The histopathological effects of mercuric chloride exposure (10, 20, 40, 80 μg/L), for 3 weeks were studied. Samples of gills, liver, intestine and kidneys were studied by light microscopy. The gill at all doses of HgCl2 showed desquamation, aneurism in secondary lamellae, lifting of the lamellar epithelium, oedema, epithelial hyperplasia and fusion of the secondary lamellae. Degenerative changes in hepatocytes, aggregation of macrophages and focal necrosis were found in the liver in dose dependent manner. Lesions in the kidney were characterized by degeneration in the epithelial cells of renal tubules, dilation of glomerular capillaries, hypertrophy of tuber epithelial cells, narrowing of tubular lumen, and hyaline degeneration. Focal degeneration of villi with swollen tips, increased goblet cells activity, leukocytic infiltration and mast cells aggregation were observed in intestinal folds.

Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis

Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation. Hu and colleagues investigated the genetic and clinical features of a large group of patients with lipoprotein glomerulopathy who carried APOE Kyoto, a major APOE variant. Their findings suggest its descent through a founder effect. Fibrate therapy in this group showed favorable results in the patient and renal survival rates.

Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation

Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.

Histological Alterations on the Structure of the Excretory Renal System in Tench (Tinca tinca) After Exposure to 17-Alpha-Ethynylestradiol

This study describes the effects of 17-alpha-ethynylestradiol (EE2) on the structure of the excretory system of the kidney in tench. Adult male tench were exposed to sub-lethal doses of EE2 (50, 100 and 500μg/kgb.w.) under semistatic conditions for a period of 30days. The nephrosomatic index and histology (including a morphometric analysis) of the kidney were examined. Histopathological lesions in the kidney of exposed tench were: dilation of glomerular capillaries and increase in the area of the renal corpuscle, hyaline degeneration in the epithelial cells of the proximal tubules leading to necrotic changes, hemorrhages in the interstitial tissue and deposits of eosinophilic material. These lesions were observed with a greater degree of severity as the exposure doses were increased. These results indicate that long-term exposure to EE2 could produce clear negative effects on the excretory system of the kidney in tench and consequently on their physiological functions.