Renal Interstitial Tissue Research Articles

Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report.

Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required.

Effects and mechanisms of Rapamycin on renal interstitial fibrosis in rats

Objective To discuss the intervention effects and mechanisms for Rapamycin on renal interstitial fibrosis in rats. Methods A total of 72 Wistar male rats were randomly divided into 3 groups, normal group(n=24), model group(n=24), treatment group(n=24). The model group and treatment group received adenine 200 mg/kg daily, and the treatment group was also given Rapamycin 5 mg/(kg·d) at the 8th day, the normal group was just given the same amount of normal saline for 6 weeks.In the end of the 2nd, 4th and 6th week, 8 rats in each group were sacrificed respectively.The expression of hepatocyte growth factor(HGF), transforming growth factor-β(TGF-β)and neutrophils gelatinases related apolipoprotein(NGAL)in each group were observed.The software of image analysis system was used for semi-quantitative analysis. Results HE and Masson staining results showed that the renal tubular were progressive swelling, and changed with interstitial fibrosis, atrophy and even necrosis in model group from 2 weeks to 6 weeks.The pathological changes of kidney were more ease in the treatment group compared with those in model group.Immunohistochemical staining results showed that HGF expression levels of renal interstitial tissue in model group and treatment group at the 2nd week were significantly higher than those of normal group(P<0.05), and were significantly decreased at the 4th week and 6th week(P<0.05); HGF expression levels of renal interstitial tissue in treatment group were significantly higher than those in model group(P<0.05). NGAL expression levels of renal interstitial tissue in model group and treatment group at the 2nd week were significantly higher than those in normal group(P<0.05), and were significantly decreased at the 4th week and 6th week(P<0.05); NGAL expression levels of renal interstitial tissue in treatment group were significantly higher than those in model group(P<0.05). TGF-β expression levels of renal interstitial tissue in model group and treatment group at the 2nd, 4th, and 6th week were significantly higher than those in normal group(P<0.05), while TGF-β expression levels of renal interstitial tissue in treatment group were significantly lower than those in model group(P<0.05). Conclusion Rapamycin could improve the rat kidney tissue pathology, relieve renal tubular expansion, and slow progression of renal interstitial fibrosis, and has certain protective effect to the kidney. Key words: Rapamycin; Renal interstitial fibrosis; Intervention mechanism

Design and Characterization of a Multicellular, Three‐Dimensional (3D) Tissue Model of the Human Kidney Proximal Tubule

Renal toxicity is a major cause of drug attrition at the clinical trial stage, and the primary site of this toxicity is within the proximal tubule. Conventional renal cell culture models lack the complexity of native tissue and thus have a limited capacity for predicting tissue‐level responses. In addition, the predictive potential of pre‐clinical animal trials is limited due to species‐specific differences between human and animal renal functions, including differential sensitivity to insults. We designed and fabricated a human three‐dimensional (3D) tissue model of the tubulointerstitial interface in which human renal interstitial tissue is supporting proximal tubule epithelial cells to facilitate their optimal morphology and function. Histological characterization demonstrated that the interstitial layer is viable and well organized, containing well‐developed CD31+ endothelial cell networks. Method optimization resulted in the formation of a polarized layer of renal epithelium on top of the interstitial layer, and formation of a basement membrane between the layers. Gene expression analysis showed that the renal tissues expressed key enzymes involved in metabolism and protein processing (CYPs, renin‐angiotensin system), suggesting that physiologic function is retained. These bioprinted human tissues may provide an opportunity to accurately study how compounds affect the renal proximal tubule as well as modeling pathogenic processes that involve tubular transport, cell‐cell interactions, and the development of tubulointerstitial fibrosis.This work was supported with internal funds.

Atazanavir nephrotoxicity.

Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential to yield its crystalline precipitation in urine and renal interstitial tissues, leading to crystalluria, urolithiasis, acute kidney injury (AKI) or chronic kidney disease (CKD). In epidemiological studies, atazanavir/ritonavir alone or in combination with tenofovir has been associated with increased risk of progression to CKD. However, renal biopsies were not provided in these studies. Case reports showing an association between atazanavir use and tubulointerstitial nephritis among HIV-infected individuals provide clues as to the potential causes of atazanavir nephrotoxicity. We now review atazanavir-related kidney disease including urolithiasis, renal dysfunction and interstitial nephritis and illustrate the review with a further case of atazanavir-associated kidney injury with sequential renal biopsies. There are two forms of atazanavir-associated tubulointerstitial nephritis: acute tubulointerstitial nephritis that may develop AKI rapidly (in weeks) after initiation of atazanavir, and chronic tubulointerstitial nephritis that may develop progressive CKD slowly (in years) with granuloma and intrarenal precipitation of atazanavir crystals as well as crystalluria. Caution should be exercised when prescribing atazanavir to patients at high risk of CKD, and therapy should be reevaluated if renal function deteriorates, especially associated with crystalluria and hematuria.

ISOLATION AND IDENTIFICATION OF BACTERIA FROM KIDNEY LESIONS IN BROILERS IN SULAIMANIA PROVINCE

A total of ninety seven broiler chicks in Sulaimania/ Kurdistan region/ Republic of Iraq, were collected from different flocks at different dates suffering from nephritis. Samples of affected kidneys were cultured on blood, Mannitol salt and MacConkey agar plates, the isolates were confirmed by API 20E system. The isolated microorganism included E.coli (89.69%), Proteus milabilis (9.27%) and Klebsiella pneumonia (1.03%). Antimicrobial susceptibility test for E.coli showed high sensitivity to Ciprofloxacin and Co-trimoxazole. Histopathological changes of the kidneys were characterized by enlargement of epithelial cells of renal tubules and pale cytoplasm, engorgement of blood capillaries in both renal glomeruli and interstitial tissues with atrophy of renal glomeruli

Effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats.

To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats. A total of 75 SD rats were randomly divided into A, B, C, D, E groups with 15 in each group. Rats in group A served as the control group received just only but tissue separation without modeling operation, while model of unilateral ureteral obstruction (UUO) was established in B, C, D, E groups. Rats in A, B group were given saline lavage placebo treatment, while rats in C, D, E groups were given diammonium glycyrrhizinate and alprostadil injection. Five rats were sacrificed 1, 2, 3 weeks after modeling, serum creatinine level of femoral venous blood was determined. Transforming growth factor - β1 (TGF - β1) and concentration of connective tissue growth factor (CTGF) were also detected by using ELISA. Line renal interstitial tissue was taken after HE staining, renal interstitial TGF - β1 and CTGF expression were detected by using immunohistochemical method. Serum creatinine levels of B, C, D, E group at different time points in were significantly higher than that of group A (P<0.05); serum creatinine levels in group B were significantly higher than that of C, D, E group at each time point (P<0.05). Serum creatinine level of Group E was significantly lower than C, D group after 2, 3 weeks (P<0.05). Rats in A group at each time point showed no significant changes in TGF - β1 and CREA concentration in serum and kidney tissues (P>0.05); while serum and kidney tissue TGF - β1, concentration of CREA, expression of rats in B, C, D, E groups showed a gradual increasing trend over time. TGF - β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups (P<0.05). TGF - β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B, C, D group at all time points in serum and kidney tissues (P<0.05). Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF - β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis, thus inhibit rat renal interstitial fibrosis process. It has synergy protective effect.

Toxopathological and immunotoxical effects of thiamethoxam in white mice

In order to investigate toxopathological and immunotoxic, effects of thiamethoxam in mice. Forty eight white mice, both sexes were divided into four groups equally, 1st group was immunized twicely with Brucella melitensis Rev1.with two weeks intervals. 2nd group was immunized as in the 1st group and at same time administrated orally with 83.73mg\kg B.W of thiamethoxam daily for 6 weeks.3rd group was administrated with thiamethoxam as in the 2nd group while the 4th group was served as control negative group. Immunological examination DTH and humoral immunity revealed that the thiamethoxam induced depressed in both arms of immune response as comparing with vaccinated non-treatment animals. The pathological examination revealed that the thiamethoxam induced, necrosis, hypertrophy of hepatocytes with multiple granulomatous lesion scatter in liver parenchyma and these lesions were progressive with period time particularly at 6 weeks post-treatment that showed marked proliferation of hepatocytes. The electron microscope examination to liver section showed lipid droplet, proliferation of mitochondria enlargement in addition to distraction of nuclear membrane and presence facular space, also there was severe hemorrhage in the renal interstitial tissue with inflammatory cells infiltration together with fibrosis of the glomeruli wall. Congestion with inflammatory cells infiltration in the red pulp of spleen, in addition to gliosis in the brain parenchyma was seen .The immunized animals showed mild pathological changes characterized by aggregation of mononuclear cells, The electron microscope to liver section showed normal organelles cell. with lymphoid hyperplasia in the spleen and in subepithelial layer of intestinal mucosa. We concluded that thiamethoxam induced toxopathological changes in the internal organs of mice and stimulated the immune response diminished its toxic effects.

High-Intensity Exercise May Compromise Renal Morphology in Rats

We investigated the renal effects of a high-intensity exercise (HIE) program based on strength training. 20 Wistar rats were randomly assigned to 2 experimental groups performing HIE or control over 12 weeks. Urinary volume, pH, citrate and calcium, and plasma urea, total proteins, creatinine, albumin, lactate dehydrogenase, creatine kinase (CK), calcium, magnesium, corticosterone and testosterone were measured. We also studied renal morphology with the Fibrosis HR(®) software. Plasma urea and CK concentrations were higher in the HIE compared to the control group (p < 0.05), whereas plasma creatinine was lower (p < 0.01). Plasma corticosterone was higher (p < 0.05) and testosterone lower (p < 0.01) in the HIE group. Except for the higher urinary volume found in the HIE group (p < 0.05), no differences between groups were observed in the rest of urinary parameters analyzed. Renal interstitial connective tissue was ~30% higher in the HIE group (p < 0.05). Glomerular tufts and mesangial areas were also higher in the HIE group (all, p < 0.05). No differences between groups were observed in the glomerular area. Overall, HIE promoted a worse morphological renal profile that might be associated with a higher risk for incidence of kidney disease in the long-term. The stress induced by the type of exercise performed could be on the basis of this worse morphological renal status.

Enlargement of bilateral kidneys by infiltration of leukemic cells in acute lymphoblastic leukemia at relapse after allogeneic hematopoietic stem cell transplantation

A 65-year-old man was admitted to our hospital because of multiple bullous lesions in the right leg in August 2011. Laboratory examinations showed pancytopenia: WBC 2,500/ll, Hb 12.3 g/dl, and Plt 10.8 9 10/ll, with a few abnormal circulating cells (3 %). Bone marrow aspiration showed a hypercellular marrow with an increase of abnormal blasts. Flow cytometric study of the blasts showed positivity for CD19, CD34, HLA-DR, and KORSA, and negativity for CD10 and CD20. Karyotype analysis using the G-banding method indicated complex abnormalities. Philadelphia chromosome was negative in fluorescence in situ hybridization (FISH) analysis. On the basis of these results, the patient was diagnosed with Philadelphia chromosome-negative, early precursor B cell acute lymphoblastic leukemia (B-ALL). After the diagnosis of B-ALL, induction chemotherapy was started. In the period of neutropenia, he developed sepsis, and wholebody computed tomography (CT) showed diffuse pulmonary infiltrative shadows, mild splenomegaly, and normal kidney size (Fig. 1a). This sepsis was controlled, and the patient achieved complete remission (CR). After 2 courses of consolidation chemotherapy, he received bone marrow transplantation from an HLA/ABO-matched unrelated donor. Engraftment was successful, and acute GVHD was not seen. Unfortunately, he showed relapse in the bone marrow at day 92. At relapse, whole-body CT indicated bilateral renal enlargement without mass formation (Fig. 1b). He received several courses of chemotherapy again, but died due to disease progression 7 months after allogeneic transplantation. Autopsy of the right kidney was performed. Pathological examination showed that numerous abnormal lymphoid leukemic cells had infiltrated into the renal interstitial tissue, although the glomeruli were intact (Fig. 2).

Characterization of Novel Flavobacterium spp. Involved in the Mortality of Coho Salmon (Oncorhynchuskisutch) in their Early Life Stages

Salmonid species in the Laurentian Great Lakes basin suffer from early mortalities that are often associated with low survival rates of swim-up fry. Coho salmon (Oncorhynchus kisutch) alevins exhibiting a spinning swimming behavior and convulsions were presented to the Aquatic Animal Health Laboratory of Michigan State University. Twelve yellow-pigmented bacterial isolates that were motile via gliding were recovered from the brains of dead and moribund fish and identified as Flavobacterium spp. (designated CS: 29-31, 34-38, 40-43). 16S rRNA sequence analysis indicated that 9 of the 12 sequences were grouped into a single clade (CS29, 31, 34-38, 40, 41) and were essentially identical over the 676 aligned bases used in the phylogenetic analysis. This clade is closely related to the eel-pathogenic Flavobacterium johnsoniae-like YO60 recovered from South Africa. The remaining three isolates, CS30, CS42, CS43 were closest to Flavobacterium sp. Wuba46 (100%), Flavobacterium sp. EP125 (100%), and Flavobacterium sp. WB 4.3-15 (99.9%), all of which were reported from European waters. Experimental challenge of five month old coho salmon fry via intra-peritoneal injection with the CS36 isolate resulted in morbidity and mortality rates of approximately 10% in the two highest infection doses. Clinical signs included tachybranchia, hemorrhages, and fin erosion. Stained tissue sections from dead and moribund fish showed degeneration of kidney tubules, edema in the renal interstitial tissues, heterophilic cellulitis and myodegenerative changes within the caudal peduncle, and a proteinaceous exudate in the coelomic cavity. Based on this study, flavobacterial infections with these isolates, which were detected for the first time in North America, can potentially cause losses in yolk sac and swim-up coho salmon fry.

Evaluation of ‘white-spotted kidneys’ associated with leptospirosis by polymerase chain reaction based &lt;i&gt;LipL32&lt;/i&gt; gene in slaughtered cows

The presence of white spots in the kidneys of cattle at slaughter (so-called white-spotted kidneys) can be an indication of infection with Leptospira, a spirochaete of public health concern because it causes zoonotic disease. In this study, 24 kidneys of 180 slaughtered cows (13.3%) showed focal to multifocal white spots at inspection. These kidneys, together with matching urine (n = 18) and blood (n = 24) samples, were examined by polymerase chain reaction (PCR) targeting the LipL32 gene. Leptospiral deoxyribonucleic acid (DNA) was detected in 19 (79.2%) out of 24 kidneys, as well as 7 (29.2%) blood and 10 (55.5%) urine samples of cows with white spots in their kidneys. Histopathological findings revealed multifocal infiltration of mononuclear cells, including lymphocytes and a few plasma cells in the renal interstitial tissues. In addition, 14 apparently normal kidneys and associated urine and blood samples were similarly examined by PCR but did not provide any positive results. In this study, high detection of leptospirosis in kidneys with interstitial nephritis suggests that Leptospira spp. are associated with white spotted kidneys. The present findings indicate that white spotted kidneys can be due to leptospirosis in this region in southwestern Iran, which indicates an increased risk of zoonotic disease. The data show that LipL32-based primers are useful for PCR-based diagnosis of leptospirosis.

The aglomerular kidney of the deep-sea gulper eel Saccopharynx ampullaceus (Saccopharyngiformes: Saccopharyngidae)

We report the presence of an aglomerular kidney in the pelagic deep-sea fish Saccopharynxampullaceus (Saccopharyngiformes: Saccopharyngidae). The thin kidney is unpaired and ribbon-like rostrally, while it is thicker caudally with a rod-like shape. Light microscopic observation of serial sections revealed no glomeruli at all. The kidney is composed of renal tubules, sinusoids and capillaries of the renal portal system and extensive interstitial lymphoid tissues. Each renal tubule is surrounded by well-developed renal portal sinusoids, and the tubules are well separated from each other. There is a large space dorsal to the vertebrae, similar to the situation in the closely related Eurypharynx pelecanoides. We consider that S. ampullaceus possesses an aglomerular kidney to gain neutral buoyancy. The urinary bladder of S. ampullaceus is a distinct vesicular structure, unlike that of E. pelecanoides.

A Case of Acute Renal Failure Caused by Hodgkin's Lymphoma: Concurrent Membranous Glomerulonephritis and Interstitial HL-CD 20 Lymphoid Infiltration

Although acute renal failure developing due to malignancies is a frequent condition, malignant renal infiltration is rarely observed among these causes. Among all malignant diseases, the hematolymphoid malignancies are the most prone to renal infiltration. Other types involved in cases with lymphoma are glomerulopathies, including immune-complex glomerular diseases such as minimal change disease, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and focal segmental glomerulosclerosis. We present herein the rare case of a 22-year-old male with both membranous glomerulonephritis and CD20 (+) lymphoid infiltration related to Hodgkin's lymphoma in the renal interstitial tissue, as detected on biopsy. The patient was treated with adriamycin, bleomycin, vinblastine, and dacarbazine protocol after pulse corticosteroid treatment, and a dramatic improvement in renal function was observed after 2 days of treatment. In this article, an exceptional renal involvement of Hodgkin's lymphoma is discussed in light of the related literature.

Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy

To elucidate the role of mast cells (MCs) in the pathogenesis of tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy specimens and serum creatinine levels, urinary protein excretion in patients with IgA nephropathy. Thirty-five patients with IgA nephropathy were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining. Monoclonal antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2 were used as primary antibodies. Ten cortical interstitial fields were randomly selected and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. In all of the control subjects, few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were positively correlated with the degree of interstitial fibrosis. A close correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha-SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a significant positive correlation was observed between the number of interstitial MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum creatinine level (r = 0.738 for MCs, r = 0.658 for alpha-SMA, r = 0.692 for PAR-2, r = 0.754 for SCF, P < 0.05). Our findings suggest that MC infiltration possibly induced by SCF in renal interstitial tissues seems to be associated with tubulointerstitial fibrosis through PAR-2 in IgA nephropathy.

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion

Objective To improve the diagnosis and treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion. Methods The clinical data of 5 cases with renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion were analyzed retrospectively. Of the 5 patients, 4 were males and 1 was female. Patient age ranged from 17 to 34 years (mean 25 years). The clinical presentations included painless gross hematuria in 1 cases, flank pain in 2 cases, no significant clinical presentation in 2 cases. Ultrasonographic examination showed solid mass in kid-ney with average diameter of 4.3 cm×4.1 cm. Among the 5 patients, contrasted CT scan revealed a solid mass in kidney with uneven enhancement in 4 cases. MRI revealed a solid mass of 5.8 cm × 6.0 cm in the right kidney with long T1 and T2 signals in 1 case. The chest X ray was normal in 4 cases, while 1 case demonstrated metastatic node in right lung. Results One case was treated with nephron sparing surgery. Other 4 cases were treated with radical nephrectomy. During the operations, the traits of tumor, such as tumor's sizes and the relationship with per-renal tissues, were found similar to other types of renal cell carcinoma. The pathological examination showed the tumor cells contained eosinophilic cytoplasm with prominent psammoma bodies in renal interstitial tissue. Immunohistochem-ical study showed that P504S, RCC, CK, and Vim were negative in all cases. They were then diag-nosed with renal cell carcinoma associated with Xp11.2 translocation/TFE3gene fusion. After 4 to 6 months of follow-up, patients remained asymptomatic and no evidence of recurrence. Conclusions Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion is a special type of kid-ney cancers. The diagnosis before operation is difficult because of lacking of specific clinical presenta-tion and image characteristics. It is mainly occurred in enfants and youths. The pathological findings usually show typical psammoma bodies in renal interstitial tissue. Key words: Kidney neoplasms; Xp11.2; TFE3; Psammoma bodies

Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response

Toll-like receptors recognising self-derived nucleic acids may participate in the pathogenesis of autoimmune diseases. Following the description of an enhanced population of toll-like receptor-9 (TLR-9) expressing auto-antibody producing B lymphocytes in active lupus, we explored the expression of TLR-9 in the renal tissue of patients with lupus. TLR-9 expression was studied in the kidneys of 12 lupus and 10 control samples from macroscopically unaffected areas of patients with renal adenocarcinoma by immunohistochemistry. A semiquantitative score was assigned separately for tubular, interstitial and glomerular expression. TLR-9 was expressed in the renal tubules and interstitial tissue in both patients with lupus and controls. Six of 12 patients with lupus with proliferative or membranous nephritis - as compared to none of the controls - exhibited both tubulointerstitial and glomerular TLR-9 expression. Biopsies with glomerular TLR-9 expression had a higher activity index (mean +/- SD, 6.3 +/- 3.5 in the presence of TLR-9 glomerular expression as compared to 1.3 +/- 1.8 in its absence, P = 0.015, t-test). This study documents for the first time the up-regulation of TLR-9 within the glomerulus of patients with lupus nephritis. Activation of TLR-9 expressing glomerular cells by endogenous nucleic acids (nucleosomes) may amplify the inflammatory response.

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction

To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO). In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis. In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05). Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.

The Effect of Seasonality on the Health and Growth of a Newly Recorded Myxobolus Species Infecting Cultured Sharp Snout Seabream (Diplodus puntazzo C.)

The prevalence, intensity, and pathology of a Myxobolus sp. affecting the kidneys of cultured Diplodus puntazzo C. during the period 2003-2005 are described. The study included data collected from the largest farm in southern Greece where a high rate of mortality due to myxosporean infection occurred. Sharp snout seabream reared in sea cages in southern Greece underwent microbiological, parasitological, and histological examinations, while measurement and identification of parasites was performed immediately after sampling. Samplings were made daily from winter 2003 to autumn 2005. Prevalence was estimated for each season (autumn, winter, spring, and summer) each year (2003, 2004, and 2005). The Myxobolus sp. was detected in high numbers and with a high prevalence of infection in the renal interstitial tissue, especially during the summer months. The growth rate of infected D. puntazzo was very slow during the study period in comparison to cultured Sparus aurata L. and uninfected D. puntazzo.

Activation of ATP-sensitive potassium channels protects vascular endothelial cells from hypertension and renal injury induced by hyperuricemia

It has been demonstrated that hyperuricemia induces reno-cardiovascular damage resulting in hypertension and renal injury because of vascular endothelial dysfunction. The pathogenesis of hyperuricemia, endothelial dysfunction, hypertension, and renal injury is progressive, and develops into a vicious cycle. It is reasonable to suggest that an antihypertensive drug with endothelial protection may block this vicious cycle. Iptakalim, a novel antihypertensive drug undergoing phase-three clinical trials, is a new ATP-sensitive potassium channel opener and can ameliorate endothelial dysfunction. We hypothesized that iptakalim could prevent hypertension and retard the pathogenesis of endothelial dysfunction and renal injury in hyperuricemic rats. In rats with hyperuricemia induced by 2% oxonic acid and 0.1 mmol/l uric acid, iptakalim prevented increases in systolic blood pressure, reduced the impairment of endothelial vasodilator function, and attenuated renal dysfunction and pathological changes in glomerular and renal interstitial tissue at 0.5, 1.5, and 4.5 mg/kg orally daily for 4 weeks. Serum levels of nitric oxide and prostacyclin, and gene expression of endothelial nitric oxide synthase in the aortic and intrarenal tissue, were increased, whereas the serum levels of endothelin-1 and gene expression of endothelin-1 in aortic and intrarenal tissue were decreased. However, serum levels of angiotensin II and renin remained unchanged in the hyperuricemic rats treated with iptakalim. In cultured rat aortic endothelial cells, amelioration of endothelial dysfunction by iptakalim was suggested by inhibition of the overexpression of intercellular adhesive molecule-1, vascular cell adhesive molecule-1, and monocyte chemoattractant protein-1 mRNA induced by uric acid, and reversal of the inhibitory effects of uric acid on nitric oxide release in a concentration-dependent manner, which could be abolished by pretreatment with glibenclamide, an ATP-sensitive potassium channel blocker. Iptakalim ameliorated hyperuricemia in this rat model by decreasing renal damage through its antihypertensive and endothelial protective properties, and it had no direct effects on anabolism, catabolism and excretion of uric acid. These findings suggest that the activation of ATP-sensitive potassium channels by iptakalim can protect endothelial function against hypertension and renal injury induced by hyperuricemia. Iptakalim is suitable for use in hypertensive individuals with hyperuricemia.

Pathogenesis of severe acute respiratory syndrome

Pathogenesis of severe acute respiratory syndrome