Interstitial Mononuclear Cell Infiltration Research Articles

Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology.

Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed in immune privileged sites, including the testis. However, in spite of considerable progress the relevance of endogenous and exogenous Gal-1 in testis pathophysiology have not yet been explored. Here we evaluated the in vivo roles of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility. A significant reduction in the incidence and severity of EAO was observed in mice genetically deficient in Gal-1 (Lgals1−/−) versus wild-type (WT) mice. Testicular histopathology revealed the presence of multifocal testicular damage in WT mice characterized by an interstitial mononuclear cell infiltrate and different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and assessment of active caspase-3 expression, revealed the prevalence of apoptotic spermatocytes mainly localized in the adluminal compartment of seminiferous tubules in EAO mice. A significant increased number of TUNEL-positive germ cells was detected in EAO testis from WT compared with Lgals1−/− mice. In contrast, exogenous administration of recombinant Gal-1 to WT mice undergoing EAO attenuated the severity of the disease. Our results unveil a dual role of endogenous versus exogenous Gal-1 in the control of autoimmune testis inflammation.

Effects of the mTOR inhibitor everolimus and the PI3K/mTOR inhibitor NVP-BEZ235 in murine acute lung injury models

The mammalian target of rapamycin (mTOR) is a key signaling kinase associated with a variety of cellular functions including the regulation of immunological and inflammatory responses. Classic mTOR inhibitors such as rapamycin or everolimus are commonly used in transplant as well as cancer patients to prevent transplant rejection or cancer progression, respectively. Noninfectious drug-induced pneumonitis is a frequent side effect in mTOR-inhibitor-treated patients. Therefore, we tested the effects of the mTOR inhibitor everolimus and the novel dual PI3K/mTOR inhibitor NVP-BEZ235 in a murine lipopolysaccharide (LPS)-induced acute lung injury model. C57BL/6 mice were treated with either everolimus or NVP-BEZ235 on two consecutive days prior to intratracheal administration of LPS. LPS administration induced a significant increase in total cell, neutrophil and erythrocyte numbers in the bronchoalveolar lavage fluid. Histological examination revealed a serious lung injury as shown by interstitial edema, vascular congestion and mononuclear cell infiltration in these mice after 24h. Everolimus as well as NVP-BEZ235 did not noticeably affect overall histopathology of the lungs in the lung injury model. However, NVP-BEZ235 enhanced IL-6 and TNF-α expression after 24h. In contrast, everolimus did not affect IL-6 and TNF-α levels. Interestingly, both inhibitors reduced inflammatory cytokines in an LPS/oleic acid-induced lung injury model. In conclusion, the mTOR inhibitors did not worsen the overall histopathological severity, but they exerted distinct effects on proinflammatory cytokine expression in the lung depending on the lung injury model applied.

Clinical and Histological Characteristics in Patients with Non-IgA Mesangioproliferative Glomerulonephritis

Background: Mesangioproliferative glomerulonephritis is the most common type of chronic glomerulonephritis (CGN). However, the clinical characteristics and prognosis are not fully understood in patients without Immunoglobulin A (IgA) deposition. To explore the clinical and pathological characteristics of patients with mesangioproliferative glomerulonephritis without IgA deposition (N-IgAN), we performed dual retrospective analyses. Methods: A single-center study was performed in 60 patients with biopsy-proven N-IgAN. 98 ageand sex-matched IgA nephropathy (IgAN) patients were randomly selected as a control group. The clinical and histopathological data at the time of renal biopsy were compared between N-IgAN and IgAN. In a second study, the data for 477 patients who had undergone maintenance renal replacement therapy (RRT) was collected and examined for the causal primary diseases. Results: Duration from onset of renal symptoms to renal biopsy in patients with N-IgAN (71.2 ± 123.3 months) was significantly longer than that in patients with IgAN (65.9±74.9 months) (p=0.0328). Urinary protein excretion in N-IgAN patients (0.6±1.1 g/gCr) was significantly lower than that in IgAN (1.0 ± 1.3 g/gCr) (p < 0.0001). Ratio of global sclerosis, segmental sclerosis, crescents, interstitial mononuclear cell infiltration, interstitial fibrosis, and tubular atrophy were significantly lower in N-IgAN patients. Of the 477 patients who had undergone maintenance RRT, 95 patients had CGN (19.9%). Among them, 37 patients had received a renal biopsy, only one patient was N-IgAN (1%). Conclusion: It appears that N-IgAN can be recognized as a benign disease entity in comparison with IgAN.

Isolation and detection of avian nephritis virus by RT-PCR from commercial broiler flocks affected with visceral gout in India

The present study reports pathomorphology, isolation and detection of Avian Nephritis Virus (ANV) by RT-PCR from a field outbreak in commercial broiler in Raipur, Chhattisgarh. Clinical signs and age wise mortality were recorded and detailed post mortem examination were performed in died chicks. The kidney tissues were collected for histopathology and isolation of virus. Clarified suspensions (10% w/v) of homogenate were prepared and inoculated into allantoic cavity of 11 day old embryonated SPF eggs. After three passages the embryos were examined for any lesions and the collected tissue samples were used for RNA extraction. The mortality was ranged from 3 to 8% in different affected flocks with 6% average mortality. During post mortem examination, the major gross lesions were renal damage and visceral uricosis. The kidneys were pale and enlarged with dilated ureters indicated acute tubular nephrosis. Microscopically moderate, multifocal, peri glomerular and interstitial mononuclear cells infiltration were the most prominent lesions. Cytoplasmic eosinophilic inclusion bodies were found in necrotized epithelial cells and desquamated tubular epithelial cells. After three passages, three embryos revealed pale swollen kidneys with full of chalky deposits and dilatation of ureters. For RT-PCR, RNA extract from pooled kidney samples of five embryos were processed. The visualization by agarose gel electrophoresis showed a product of expected size of 325 bp Avian Nephritis Virus (ANV) specific product. The RT-PCR used in the present study can be a potential tool for routine diagnosis of samples submitted from cases of gout and nephropathy in chickens.

Protective Effect of Probiotic Bactosac Against Induced Sub Chronic Lead Toxicity in Broiler Chicks

ABSTRACT: The protective role of the probiotic Bactosac® in minimizing the negative oxidative stress and the biochemical and morphological alterations induced by sub-chronic exposure of broiler chicks to 2500 ppm lead (pb) acetate in drinking water for 5 consecutive weeks was evaluated. Results revealed that body weight in Pb acetate treated broiler chicks was significantly decreased (47 %). However, the co-administration of Bactosac® with Pb acetate succeeded to improve this percent to 19.62 % in comparison to control group. Also, antioxidants parameters of hepatic and renal tissues were significantly changed in Pb acetate exposed chicks, where the GSH concentration was significantly enhanced, while, GST and CAT activities, were significantly inhibited. Lipid peroxidation indicator MDA was also significantly increased. Activity of hepatic transaminases ALT and AST were significantly elevated in Pb acetate treated chicks while serum creatinine and blood urea showed no significant changes. The accumulation pattern of Pb in treated chicks revealed that the highest and significant concentration was recorded in bone (160 times), then kidneys (13 times), followed by Liver (2.2 times) and brain (1.6), while muscles showed the lowest (1.3 times) accumulation to Pb when compared to control values. Histopathological examination revealed presence of hepatocytic degeneration, necrosis and hemorrhages, as well as, vascular congestion of the inter tubular blood vessels, interstitial mononuclear cell infiltration, glomerular hypercellularity and some areas of inter tubular mononuclear cell infiltrations and aggregations in kidneys of pb-intoxicated birds. Concurrent treatment of Bactosac® with Pb acetate in drinking water of broiler chicks revealed a significant improvement of the previous antioxidant parameters, liver transaminases, accumulation pattern of Pb and morphological alterations. It is concluded that probiotics Bactosac® play an important and promising tool to prevent/reduce pb toxicity in broiler chicks.

Renal changes in the early stages of diet-induced obesity in ovariectomized rats.

The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-kappaB), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-kappaB.

Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.

Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

Clinical and Pathological Study of Polyomavirus-Associated Nephropathy after Renal Transplantation

Polyomavirus infection has emerged as an important cause of polyomavirus-associated nephropathy (PVAN) leading to allograft dysfunction and loss. The aim of this study is to investigate pathological features and clinical characteristics of PVAN. We prospectively investigated 351 renal allografts performed in Jinling Hospital. PVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. 31 patients were diagnosed with PVAN (8.8%). The patients with PVAN typically presented as allograft dysfunction with an asymptomatic rise in serum creatinine about 3 to 39 months posttransplant. Urinary decoy cells were positive in 4 patients (12.9%). The histologic changes of PVAN are not pathognomonic and can be mistaken for allograft rejection, i.e. tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis, tubular atrophy and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining is positive in allograft. CD3, CD4, CD8, CD68 positive cells are increased in PVAN group than the non-PVAN group, but none of HLA-DR and IL-2R expression is positive in PVAN patients. MPA AUC 0-12 and TAC trough levels are increased in PVAN group than non-PVAN group at biopsy. We have treated 31 patients with biopsy-proven PVAN with leflunomide. Increased intensity of immunosuppression appears to increase the likelihood of PVAN. The definitive diagnosis of PVAN requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of PVAN.

A Case of Acute Kidney Injury in a Patient with Pulmonary Tuberculosis Receiving Ethambutol Therapy

Ethambutol is commonly used as a first-line drug for the treatment of tuberculosis. The most serious adverse effect of ethambutol therapy is optic neuropathy. However, ethambutol-induced acute kidney injury is extremely rare. We report herein a case of acute kidney injury secondary to ethambutol-associated acute interstitial nephritis. A 65-year-old man with pulmonary tuberculosis presented with a > 7-day history of nausea and vomiting. He had begun antituberculosis medications including ethambutol 3 weeks previously. His laboratory findings showed elevated blood urea nitrogen and serum creatinine levels (32.6 and 3.6 mg/dL, respectively). Examination of percutaneous renal biopsy specimens showed diffuse interstitial mononuclear cell infiltration with mild interstitial edema. The patient was treated by cessation of ethambutol and supportive care. His renal function completely recovered (creatinine, 1.1 mg/dL) and his clinical symptoms improved. (Korean J Med 2014;87:352-356)

Dramatic early event in chronic allograft nephropathy: increased but not decreased expression of MMP-9 gene

ObjectiveThe infiltration of mononuclear cells and replication and migration of smooth muscle cells (SMCs) from media into the intima in the vascular wall are the cardinal pathological changes in the early stage of chronic allograft nephropathy (CAN). But the mechanism is unclear. Therefore we investigated the role of matrix metalloproteinase 9 (MMP-9) and its interaction with TGF-beta1, tubulointerstitial mononuclear cells infiltration and migration of SMCs in the early stage of CAN.MethodsKidneys of Fisher (F334) rats were orthotopically transplanted into bilaterally nephrectomized Lewis (LEW) recipients. To suppress an initial episode of acute rejection, rats were briefly treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days. Animals were harvested at 12 weeks after transplantation for histological, immunohistochemistry and molecular biological analysis.ResultsThe expression of MMP-9 was up-regulated in interstitium and vascular wall in the early stage of CAN, where there were interstitial mononuclear cells infiltration and SMCs migration and proliferation. Moreover the expression of MMP-9 were positively correlated with the degree of interstitial mononuclear cells infiltration, the quantity of SMCs in arteriolar wall, and also the increased TFG-beta1 expression in the tubulointerstitium and arteriolar wall.ConclusionsMMP-9 may play an important role in the mechanism of pathological changes during the earlier period of CAN.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1582313332832700.

A case of polymyositis associated with Hashimoto's thyroiditis

A case of polymyositis associated with Hashimoto's thyroiditis

3 Year Immunological Follow Up of the First Bilateral Arm Transplant World Wide

Introduction: On July 27 - 28, 2008 for the first time worldwide two arms were grafted to the 54-year-old patient. He had lost his two arms in a corn chopping machine accident 6 years before. Attempts to use a myoelectric prosthesis failed due to the weight of the device and the length of the stumps. After thorough physical and psychological examination he was put on a waiting list with EUROTRANSPANT. After a suitable local donor with a good compatibility regarding age, gender, skin color, height, weight and length of the arms was found, immunological investigations showed blood group identity, a five allele HLA mismatch and a negative crossmatch. Immunosuppression: Initial immunosuppression consisted of intravenous application of 500 mg Methylprednisolone, antithymocyte globulin at a dose of 1.25 mg per kilogram body weight and Tacrolimus at a dose of 0.25 mg per kilogram body weight. Topical Tacrolimus and Mycophenolate Mofetil (1.5 g BID) started on POD 1. Intravenous thymoglobulin administration was continued for a total of five days. Tacrolimus dosis was adjusted to a trough level from 10-15 ng/ml. Immunological and clinical follow-up consisted of daily examination of the skin, biopsies from both arms once a week and MRI every two weeks. Result: No clinical or histological signs of rejection were visible within the first three month. Then a focal rash on the left upper arm in combination with focal petechiae on both fingers occurred. Biopsies showed typical signs of mild rejection (Banff II) with interstitial swelling and mononuclear perivascular cell infiltration. As intravenous injection of 250 mg methylprednisolone on three consecutive days could not solve the problem, subcutaneous injection of efalimzumab (0.5 mg/kgBW weekly for 3 months) was started. Two weeks later the lesions were completely resolved. After six months again a rash occurred on both upper arms. Biopsies revealed signs of rejection grade Banff II-III. Anti thymocyte globuline (ATG-F; Fresenius) was administered intravenously on five consecutive days. Within two weeks all clinical and histological signs of rejection disappeared. Since then no signs of rejection occurred, the current immunosuppression regime is tacrolimus (Trough level 5-8ng/ml), MMF and steroids (5mg/day) Discussion: With this first bilateral arm transplantation we have shown that the transplantation of a large amount of composite tissue is possible. At no time point signs of graft versus host disease could be detected despite a huge amount of bone marrow transplanted with both upper arms. Maintenance immunosuppression is not different from the medication renal transplant recipients receive fort the long run. Since the second rejection episode 6 months after the transplantation no further immunological problems evolved.

Immunopathology, Diagnosis, and Management of Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by a wide variety of organic particles and certain small-molecular weight chemical compounds that provoke an exaggerated immune response in susceptible individuals. The clinical manifestations are heterogeneous and have been classically described as acute, subacute and chronic. The chronic form has an insidious onset over a period of months or years, with progressive dyspnea and often evolves to fibrosis. The pathology is characterized by a bronchiolocentric interstitial mononuclear cell infiltration, nonnecrotizing poorly formed granulomas, cellular pneumonitis and variable degrees of fibrosis. However, morphological diagnosis of HP is complicated because the subacute/chronic forms may be difficult to distinguish from idiopathic pulmonary fibrosis/usual interstitial pneumonia and nonspecific interstitial pneumonia. In general, diagnosis of HP represents a challenge for clinicians that need to weigh a constellation of clinical, laboratory, radiographic and (when available) pathological evidence for each patient to assess the certainty of the diagnosis. The cornerstone of therapy is antigen avoidance. Although clinical trials are scanty, corticosteroids are usually indicated based upon expert opinion. In this review we summarize the current evidence regarding the diagnostic criteria and therapeutic strategies as well as the immunopathological mechanisms putatively implicated in the development of the disease.

Comparative Study on the Effects of Chloroquine and Artesunate on Histopathological Damages Caused by Plasmodium berghei in Four Vital Organs of Infected Albino Mice

The aim of the present study was to investigate the positive influence of chloroquine and artesunate on the pathological damages caused by Plasmodium berghei on vital organs of mice in an established infection. Healthy adult albino mice with average weight of 25 g were used for the study. Treated group was administered orally with 100 mg/kg of chloroquine and artesunate, respectively. Control animals were given water for the same period. Histological examination of the liver, spleen, lungs, and kidney revealed absence of accumulation of iron (haemosiderosis) in the liver, thickened alveolar wall, and interstitial mononuclear cells infiltration in the lungs of the artesunate group, while absence of emphysema in the lungs and megakaryoblast hyperplasia in the spleen was observed in the chloroquine group. Lymphoid hypoplasia in the chloroquine group and megakayoblast hyperplasia in the artesunate group were observed but not in the control group. Thus, the use of these drugs especially under the practice of self-medication should be prohibited in lands where they are still in use as antimalaria medicine.

Exercise may offset nicotine-induced injury in lung tissue: A preliminary histological study based on a rat model

ABSTRACTNicotine appears to be the primary pharmacologic agent that causes smoking-related pulmonary diseases. An understanding of the effect of nicotine on lungs is essential to develop interventions that can be used to counter smoking-related diseases. Further, it is shown that physical exercise may partially reverse smoking-induced pathological changes in experimental animals. Hence, this study focuses on the pathological changes in rat lung following nicotine administration and the role of exercise in reversing the nicotine-induced lung injury. This is a randomized controlled trial with 3 groups of rats. Control (CG), nicotine-exposed (NG), and nicotine-exposed and exercise group (NEG). Control group received no intervention. Both NG and NEG were given 1.5 mg/kg nicotine base, daily, subcutaneously, but NEG were also subjected to an intensive daily swimming protocol. The rats were sacrificed and the lung tissue was processed for light and transmission electron microscopic and immunohistochemical studies. Compared with the control group, the nicotine group showed enlargement and destruction of the alveolar septum, cellular hyperplasia and interstitial fibrosis, and interstitial mononuclear cell infiltration with increased intraluminal macrophages. There was only modest morphological change between the nicotine administered and nicotine and exercise groups. Expression of superoxide dismutase (SOD) and catalase showed a mild increase in the NEG, whereas glutathione peroxidase (GPX) showed mild and moderate increase in the expression in the NG and NEG, respectively. This study shows that nicotine induces substantial pathological changes in the lung and prolonged exercise may have some beneficial effects in partially reversing the nicotine-induced lung injury by inducing the expression of antioxidants.

Surveillance Renal Allograft Biopsy on Diagnosis of BK Virus Nephropathy in Chinese Renal Transplant Recipients

Objective: We prospectively investigated 121 renal allograft biopsy specimens performed in our center. Methods: BKVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. Results: Of the 121 patients, nine were diagnosed with BKVAN (7.4%). Nine patients whith BKVN classically presents as allograft dysfunction with an asymptomatic rise in serum creatinine, about 3 to 39 months posttransplant. Urinary decoy cells are positive in two patients (22.2%). The histologic changes of BKVN are not pathognomonic, and can be mistaken for allograft rejection, ie, tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis and tubular atrophy, and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining were positive in allograft. Graft loss occurred in one patient and the other 8 showed progressive allograft dysfunction. Conclusion: The definitive diagnosis of BKV disease requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of BKVAN.

Interstitial granuloma fungoides： a case report

A 36-year-old woman presented with a 3-year history of pruritic erythema and scaling on the trunk and extremities. Dermatological examination revealed ill-defined light pink maeules with white lamellar scales on the chest, abdomen and buttocks. Histologically, there was a focal mononuclear cell infiltrate in the superficial dermis, with the epidermotropism of some cells and mild atypia of epidermotropic cells, as well as an interstitial mononuclear cell infiltrate and mild deposition of mucin between the collagen fibers in the middle dermis. CD3 and CD4 were expressed by scattered mononuclear cells infiltrating the upper and middle dermis. Based on these data, the patient was diagnosed with interstitial granuloma fungoides. Key words: Granuloma fungoides; Neoplasms by histologic type

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake

High salt intake (HS) is a risk factor for cardiovascular and kidney disease. Indeed, HS may promote blood-pressure-independent tissue injury via inflammatory factors. The lipid-lowering 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors exert beneficial lipid-independent effects, reducing the expression and synthesis of inflammatory factors. We hypothesized that HS impairs kidney structure and function in the absence of hypertension, and these changes are reversed by atorvastatin. Four groups of rats were treated for 6 wk in metabolic cages with their diets: normal salt (NS); HS, NS plus atorvastatin and HS plus atorvastatin. We measured basal and final body weight, urinary sodium and protein excretion (U(Prot)V), and systolic blood pressure (SBP). At the end of the experimental period, cholesterolemia, creatinine clearance, renal vascular reactivity, glomerular volume, cortical and glomerular endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-β1 expression were measured. We found no differences in SBP, body weight, and cholesterolemia. HS rats had increased creatinine clearence, U(Prot)V, and glomerular volume at the end of the study. Acetylcholine-induced vasodilatation decreased by 40.4% in HS rats (P < 0.05). HS decreased cortical and glomerular eNOS and caused mild glomerular sclerosis, interstitial mononuclear cell infiltration, and increased cortical expression of TGF-β1. All of these salt-induced changes were reversed by atorvastatin. We conclude that long-term HS induces inflammatory and hemodynamic changes in the kidney that are independent of SBP. Atorvastatin corrected all, suggesting that the nitric oxide-oxidative stress balance plays a significant role in the earlier stages of salt induced kidney damage.

Detection and characterization of avian nephritis virus in ducklings

The first evidence of avian nephritis virus (ANV) in ducks is described. A diagnostic investigation was performed on three duck farms in Croatia. Samples from dead-in-shell ducklings and ducklings aged 30 days were collected and prepared for molecular and histopathological examination. Intestinal and liver samples were tested by polymerase chain reaction (PCR) for the presence of ANV, duck enteritis virus, duck hepatitis virus 1 and Derzsy's disease virus. Multiple tissues were collected for histological examination and lesions were found to be confined to the kidney and intestine. Moderate focal interstitial and periglomerular mononuclear cell infiltrates (mostly lymphocytes and plasma cells) were detected in the kidney. The duodenum showed rather diffuse pericryptal mononuclear cell hyperplasia (lymphocytes) and fibroplasia. ANV was detected by PCR in all the intestinal samples, while no other viruses were found. Sequence comparisons of the portion of the open reading frame 1b encoding the RNA-dependent RNA polymerase gene confirmed that the virus detected and sequenced from ducklings shared high nucleotide and amino acid identities with ANV-1. Additional work is required to determine the clinicopathological significance of ANV infection in ducks.