Severity Of Histological Lesions Research Articles

Duodenal and colonic mucosal S100A8/A9 (calprotectin) expression is increased and correlates with the severity of select histologic lesions in dogs with chronic inflammatory enteropathy

BackgroundCalprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE.ResultsMucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes.ConclusionsThese results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.

The Histological and Biochemical Assessment of Monoiodoacetate-Induced Knee Osteoarthritis in a Rat Model Treated with Salicylic Acid-Iron Oxide Nanoparticles.

Iron oxide nanoparticles (IONPs) represent an important advance in the field of medicine with application in both diagnostic and drug delivery domains, offering a therapeutic approach that effectively overcomes physical and biological barriers. The current study aimed to assess whether oral administration of salicylic acid-functionalized iron oxide nanoparticles (SaIONPs) may exhibit beneficial effects in alleviating histological lesions in a murine monoiodoacetate (MIA) induced knee osteoarthritis model. In order to conduct our study, 15 Wistar male rats were randomly distributed into 3 work groups: Sham (S), MIA, and NP. At the end of the experiments, all animals were sacrificed for blood, knee, and liver sampling. Our results have shown that SaIONPs reached the targeted sites and also had a chondroprotective effect represented by less severe histological lesions regarding cellularity, altered structure morphology, and proteoglycan depletion across different layers of the knee joint cartilage tissue. Moreover, SaIONPs induced a decrease in malondialdehyde (MDA) and circulating Tumor Necrosis Factor-α (TNF-α) levels. The findings of this study suggest the therapeutic potential of SaIONPs knee osteoarthritis treatment; further studies are needed to establish a correlation between the administrated dose of SaIONPs and the improvement of the morphological and biochemical parameters.

Development of a multivalent adjuvanted inactivated vaccine against variant arthrotropic avian reoviruses.

Variant avian reoviruses (ARVs) are economically important emerging pathogens of poultry, which mainly affect young broiler chickens and cause significant production losses. Currently, there are no effective commercial vaccines available for control and prevention of emerging variant ARVs. In this study, monovalent inactivated adjuvated (20% Emulsigen D) broiler breeder vaccines containing antigens from ARV genotype cluster (C) group -2, -4, -5, or -6, and a multivalent vaccine containing antigens from all the four indicated genotypic cluster groups were developed and evaluated for their efficacy in protecting broiler progenies against homologous or heterologous ARV challenge. The use of monovalent or multivalent inactivated vaccines in a prime-boost immunization strategy induced the production of ARV specific antibodies in broiler breeders. The maternal antibodies were effectively transferred to broiler progenies. Broiler progenies obtained from immunized breeders demonstrated milder clinical symptoms and reduced gross and histopathological lesions after homologous ARV challenge. More severe gross and histological lesions were observed in challenged progenies from unvaccinated broiler breeders. However, cross protection was not observed when either of the monovalent-vaccine groups were challenged with a heterologous virus. In addition, the progenies from the unvaccinated ARV challenged control or heterologous ARV challenged vaccinated groups had significantly reduced body weight gain (p < 0.01) than the unchallenged-control, challenged-multivalent, or homologous ARV-challenged monovalent vaccine groups. However, homologous ARV challenged progenies in the multivalent or monovalent vaccine groups had similar body weight gain as the control unchallenged group with significantly reduced viral load (p < 0.01) in the gastrocnemius tendon tissue. This study indicates that broad-spectrum protection of broiler progenies from variant ARV infections is feasible through the development of multivalent vaccines after proper characterization, selection and incorporation of multiple antigens based on circulating ARV genotypes in targeted regions.

Temporal changes in pathology and viral RNA distribution in guinea pigs following separate infection with two New World Arenaviruses.

Numerous arenaviruses have been identified throughout the Americas and a subset of these viruses cause viral hemorrhagic fever in humans. This study compared the pathology and viral RNA distribution in Hartley guinea pigs challenged with two human-disease causing New World arenaviruses, Junin virus (JUNV) or Guanarito virus (GTOV). Histopathologic analysis and RNA in situ hybridization revealed similar pathology and viral RNA distribution for both groups of animals challenged with either JUNV or GTOV on days 3, 7, 10 and 12 post exposure (PE). Gross lesions were first observed on day 7 and primarily involved the lungs and liver. The most severe histologic lesions occurred in the lymph nodes, spleen, and thymus and included lymphoid depletion and necrosis which increased in severity over time. Extensive necrosis was also observed in the bone marrow on day 12. Minimal to mild inflammation with and without necrosis was observed in the choroid plexus of the brain, choroid of the eye, intestinal tract, lung and adrenal gland. Significant liver lesions were rare, consisting predominantly of hepatocyte vacuolation. Viral RNA labeling was identified in nearly all organs examined, was often extensive in certain organs and generally increased over time starting on day 7. Our data demonstrate the guinea pig may serve as a useful model to study New World arenavirus infection in humans and for the evaluation and development of medical countermeasures.

Resistive index and kidney biopsy: what correlation in chronic kidney disease?

Introduction. Chronic kidney disease (CKD) represents a global public health problem. Its progression to the end stage is based on the existence and severity of histological lesions, especially interstitial fibrosis and vascular lesions, and exposes a high risk of mortality and cardiovascular events. Renal biopsy remains the reference examination allowing an accurate evaluation of the importance of fibrosis and remains an invasive and risky examination. The assessment of the risk of progression of CKD by a non-invasive examination would be of capital interest to the nephrologist in order to reinforce nephroprotection measures to delay the progression of renal disease and reduce the risk of cardiovascular events, which represents the first cause of mortality in this population. The value of the resistive index (RI), measured by an echo-doppler, seems to be important. The primary objective of this work was to evaluate the correlation between the value of the RI and the severity of the histological lesions. Secondary objectives were to evaluate the correlation of RI with CKD progression, cardiovascular mortality, and to define a prognostic threshold for progression. Material and method. This is a prospective monocentric study including 104 patients hospitalized in the nephrology department of the regional military university hospital of Constantine during the period April 2014-January 2019, presenting with CKD and scheduled for a renal biopsy for diagnostic purposes. RI measurement was performed 24-48 hours before this procedure. Results. We showed that there is a positive and statistically significant correlation of RI with age (r=0.38, p &lt; 103), the number of cardiovascular risk factors (r=0.39, p &lt; 103),systolic blood pressure (r=0.39 , p &lt; 103) and pulse pressure ( r=0.51 , p &lt; 103), percentage of glomerulosclerosis (r=0.51, p &lt; 103), percentage of interstitial fibrosis ( r=0.43 , p &lt; 103) and vascular damage (p &lt; 103). While there is a negative correlation with initial eGFR (r= -0.52 , p &lt; 103) and to a lesser degree with the combined size of the two kidneys (r= -0.26 , p &lt; 103), no correlation was observed with diastolic blood pressure, proteinuria (proteinuria / creatinuria ratio) and the use of antiproteinuric treatment. Switching to renal replacement therapy (RRT) and cardiovascular mortality were associated with the highest RI. Beyond a threshold value of 0.65, histological lesions are more pronounced with a worse evolution of CKD. Conclusion. This study underlines that RI is a non invasive marker of progression and the interest to propose it as a prognostic criterion in the management of chronic kidney disease.

The pathology of co-infection with Usutu virus and Plasmodium spp. in naturally infected Eurasian blackbirds (Turdus merula)

Usutu virus (USUV) is a mosquito-borne zoonotic flavivirus causing mortality in Eurasian blackbirds (Turdus merula) in Europe. In dead blackbirds, avian malaria co-infection due to mosquito-borne hemosporidians (e.g., Plasmodium spp.) has been reported. In humans, a similar co-infection of a flavivirus, Dengue virus, and Plasmodium spp. is causing increased severity of clinical disease. Currently, the effects of co-infection of arboviruses and hemosporidians in blackbirds remain unclear. This study investigates the rate of USUV and Plasmodium spp. co-infection in found-dead blackbirds (n = 203) from 2016 to 2020 in the Netherlands. Presence of Plasmodium spp. was evaluated by cytology (43/203; 21,2%), histopathology (94/186; 50,5%) and qPCR (179/203; 88,1%). The severity of histological lesions in USUV and Plasmodium spp. co-infected dead blackbirds (121/203; 59,6%) were compared with those in Plasmodium spp. single-infected cases. Additionally, since no knowledge is present on the infection rate on live birds and mosquitoes in the Netherlands, a small group of live blackbirds (n = 12) and selected in the field-collected mosquito pools (n = 96) in 2020 were tested for the presence of Plasmodium spp. The latter was detected in the tested live blackbirds by qPCR (8/10; 80%), and cytology (3/11; 27,3%) and in the mosquito pools by qPCR (18/96; 18,7%). For this study, co-infection between USUV and Plasmodium spp. was observed only in the dead blackbirds. The high Plasmodium spp. presence, associated with lower lesions score, in single infected found dead birds suggest a predominantly smaller pathogenic role as single agent. On the other hand, the higher histological lesion scores observed in USUV and Plasmodium spp. co-infected birds suggests a major pathogenic role for the virus or an increased severity of the lesions due to a possible interplay of the two agents.

In Vitro Investigation of the Interaction of Avian Metapneumovirus and Newcastle Disease Virus with Turkey Respiratory and Reproductive Tissue.

In poultry, several respiratory viral infections lead to a drop in egg production associated with high economic losses. While the virus-host interactions at the respiratory epithelium are well studied, less is known about these interactions in the oviduct. To investigate possible differences between virus infections at these epithelial structures, we compared the interactions of two important poultry viruses on turkey organ cultures. Two members of the order Mononegavirales, the Avian Metapneumovirus (AMPV) and the Newcastle disease virus (NDV), were selected to conduct the in vitro experiments since these viruses can infect both the trachea and oviduct. In addition, we used different strains of these viruses, a subtype A and a subtype B strain for AMPV and the NDV strains Komarow and Herts'33, to detect possible differences not only between the tissues but also between different viral strains. Turkey tracheal and oviduct organ cultures (TOC and OOC) were prepared to investigate viral replication, antigen localisation, lesion development, and the expression pattern of interferon-λ and importin-α isoforms. All viruses replicated more efficiently in the oviduct than in the tracheal epithelium (p < 0.05). In addition, we observed higher expression levels of both, IFN-λ and importin-α in OOCs compared to TOCs. Our results indicated strain-dependent differences, with the AMPV-B- and Herts'33 strains being more virulent in organ cultures than the AMPV-A- and Komarow strains, based on the higher viral genome loads, more severe histological lesions, and higher upregulation of IFN-λ. Overall, our findings reveal tissue- and virus strain-dependent differences, which may have consequences for disease development in the host tissue and, subsequently, possible treatment strategies.

Toxic effects of chromium chloride on hematology and histopathology of major carp (Labeo rohita)

Heavy metal contamination caused by human activities is a major threat to aquatic organisms. Therefore, a 28-day trial was designed to evaluate the hematological and histological changes in Labeo rohita exposed to chromium chloride. For this purpose, 240 fish (Labeo rohita) were randomly selected and divided into four groups. Three groups were treated with a sublethal waterborne concentration of chromium (37, 22, and 11 mgL−1); the fourth group was chromium-free control (0 mgL−1). Results demonstrated that noted values of hematological parameters, such as mean cell hemoglobin, red blood cells, hematocrit, platelets, and hemoglobin, were decreased significantly (P < 0.05) in experimental groups compared with control, while mean cell volume and white blood cells were increased. On the 28th day, a decline was observed in white blood cell values. The severity of histological lesions in the liver, kidney, and gills increased as the concentration and duration of chromium exposure increased. No histological change was observed in the control (T0), while T1 showed more severe changes than T2 and T3. Those results suggest that long-term exposure to chromium chloride causes adverse effects on the hematology and histology of major carp, Labeo rohita.

Coinfection with porcine circovirus type 2 and Glaesserella parasuis serotype 4 enhances pathogenicity in piglets

Coinfection of Porcine circovirus type 2 (PCV2) and Glaesserella parasuis type 4 (GPS4) is widespread clinically, resulting in high morbidity and mortality, however, interactions between the two pathogens during coinfection and the coinfection pathogenesis are poorly understood. In this study, a piglet model coinfected with PCV2 and GPS4 was established; coinfection of the piglets' group showed more obvious symptoms, such as high fever and emaciation, and more severe histological lesions appeared in various organs. Importantly, piglets in the coinfection group produced lower levels of PCV2 and GPS4 antibodies, and showed high levels of inflammatory cytokines, TLR2, and TLR4, while the levels of CD4, CD8, MHC II, costimulatory molecules, and IL-12p40 were decreased. In addition, a model of macrophage 3D4/21 cells coinfection with PCV2 and GPS4 was established, coinfected cells exhibited increased expression of the cytokines IL-6, IL-8, TNF-α, IL-1β, and the receptors TLR2, TLR4, while decreased MHC II. We further demonstrate that cytokine production is associated with the activation of NF-κB and NLRP3 inflammasome signaling pathways, and TLR4 is also involved. Altogether, our findings suggest that coinfection with PCV2 and GPS4 exacerbates the inflammatory response, resulting in severe tissue damage, and probably impaired macrophage antigen presentation and T cell activation, resulting in immune dysregulation, aggravating host infection.

Avaliação da troponina I e C em equinos intoxicados por salinomicina

ABSTRACT: Ionophores are antibiotics frequently used in animals of production. The most common are monensin, salinomycin, narasin, and lasalocid. The equine species is highly susceptible to ionophores poisoning. The present study aimed to analyze the serum use of cardiac troponin I (cTnI) and the anti-troponin C immunohistochemistry (IHC) technique (anti-cTnC) as a diagnostic tool for cardiac injuries in horses spontaneously poisoned by salinomycin. Seven horses were affected by a disease lasting for 6-72 hours. Three horses recovered. The primary morphological lesions reported in the four necropsied horses that died spontaneously were necrosis of the myocardium and skeletal muscle. Immunohistochemistry for anti-cTnC was performed in selected sections of the cardiac muscle from the equine submitted for necropsy. A decrease in cTnC expression in the cytoplasm of cardiomyocytes was noticed in all four necropsied horses. Samples of serum from six horses tested for cardiac troponin I levels; the most expressive values were mainly in horses with more severe cardiac histological lesions. The serum detection of cTnI can be considered a good marker to determine cardiac damage in horses intoxicated with salinomycin with a clinical evolution of 48 hours or more. The anti-cTnC IHC aided in the detection of cardiac injury in horses independent of clinical evolution.

Renal Histologic Findings in Necropsies of Type 2 Diabetes Mellitus Patients

Background Very few studies have analyzed early histologic lesions of diabetic nephropathy (DN) in patients without signs of clinical involvement (microalbuminuria). In this study, we analyzed renal histologic lesions in necropsies of diabetic patients with or without previous signs of DN. Methods Histological material was analyzed from 21 autopsies of type 2 diabetes mellitus (T2DM) patients (9 with albuminuria and 12 without albuminuria) and 4 controls. Histologic lesions were evaluated according to the Tervaert classification. Results Kidneys of diabetic patients presented significantly higher scores in most histologic indices analyzed (glomerular basal membrane thickening, mild and severe mesangial expansion, nodular sclerosis, interstitial fibrosis, and tubular atrophy) than in nondiabetic controls (p < 0.01 in all cases). In contrast, no significant differences were detected between histologic scores when comparing the 21 diabetic patients with and without albuminuria. A significant percentage of cases without albuminuria showed moderate to severe histologic lesions, particularly severe mesangial expansion and severe glomerular vascular lesions. No significant differences were found in age, blood pressure, diabetes vintage, BMI, HbA1c, cholesterol, triglycerides, or treatments between the two (albuminuric vs. nonalbuminuric) T2DM patient groups. Conclusions Our data suggest that histologic lesions of DN are present in the early stages of the disease, even without albuminuria presence. More precise and earlier metabolic control is recommended in T2DM, and monitoring of risk factors can play a role in DN development.

Nephrotic Syndrome with Focal Segmental Glomerulosclerosis Histological Feature: A Case Report

Introduction: Nephrotic syndrome is a clinical syndrome of heavy proteinuria and hypoalbuminemia or hypoproteinemia. Renal biopsy is fundamental to assess not only the type but also the degree of disease activity. The overall prognosis and response to treatment often depend on the severity of histological lesions and their reversibility.1,2 Case Presentation: An eighteen years old man with nephrotic syndrome and planned for a kidney biopsy. This case showed a patient with swollen face (especially on the cheek). On Biopsy results showing the glomerulus proliferation of cells and mesangeal matrix, adhesions in (50%) glomerulus, focal sclerosis in some glomeruli, erythrocyte cells visible in the urinary space and thickening of the basement membrane in some glomeruli, partially atrophic tubules, visible erythrocytes in the tubular lumen. Conclusion: An eighteen years old man with nephrotic syndrome with cushing syndrome and hypokalemia who had a renal biopsy. The histological feature from the renal biopsy was focal segmental glomerulosclerosis. The underlying cause of FSGS is still unclear. Assessing the diagnosis and etiology become important to direct the subsequent clinical approach and therapy

Severe lupus nephritis in the present days.

Lupus nephritis (LN) is one of the most frequent and severe organ manifestations of systemic lupus erythematosus (SLE) that is a chronic autoimmune disease. Despite improvement in patient and renal prognosis, the disease continued to be associated with a high rate of end stage kidney disease. Along the last decades, it seems that the epidemiology of LN and its clinical presentation have progressively changed. The forms with renal insufficiency at presentation seem to have progressively reduced in developed countries in favour of more mild clinical presentations with urinary abnormalities only. To this clinical change does not correspond a less severe histological lesions, in fact, the extent of active lesions at kidney biopsy are unchanged, whereas chronic lesions are becoming less frequent and less severe. Meanwhile, new types of severe LN defined by the variable association of demographic, clinical, histological characteristics at diagnosis or during the follow-up are gradually emerging and require attention in assessing the therapy and prognosis. During the last years, randomized controlled trials have reported the efficacy of new drugs in association with standard therapy to improve the rate of short- and medium-term renal response. One of the advantages is that these results were obtained with reduced dosage of corticosteroids whose protracted use is associated with increase of chronic organ damage. Optimization of therapeutical strategies, tailored on the demographic clinical and histological characteristics, with combination of old and new drugs are urgently needed for severe LN.

CORRELATION BETWEEN CLINICAL AND PATHOLOGIC FEATURES OF DIABETIC NEPHROPATHY

Background: Diabetic nephropathy is the most common cause of end stage renal disease in Thailand. Renal biopsy remains the gold standard investigation to diagnose and classify diabetic nephropathy.&#x0D; Objectives: In this study, we aimed to evaluate the correlation between clinical parameters and renal pathology classification among patients with type 2 diabetic and nephropathy.&#x0D; Methods: We conducted an observational study and enrolled 63 patients undergoing renal biopsy between 1 January 2014 and 31 December 2018. Pathologic classification established by the Renal Pathology Society was used to assess the severity of histologic lesions in diabetic nephropathy. Clinical parameters including age, sex, duration, presence of diabetic retinopathy, blood urea nitrogen, creatinine, urine protein creatinine ratio, fasting plasma glucose and hemoglobin A1C were collected.&#x0D; Results: At the time of biopsy, mean age was 50.25±11.46 years. Median duration of diabetes mellitus was 10 years with interquartile range (IQR) 3.75-12.00 years, mean serum creatinine was 2.44 ± 1.31 mg/dL and estimated glomerular filtration rate was 22.41±12.16 mL/min/1.73 m2. Based on the glomerular classification, 1 patient (1.6%) was in class I, 16 (25.3%) in class II, 25 (39.7%) in class III and 21 (33.3%) in class IV. Using multivariate analysis, class IV was associated with rising serum creatinine compared with class II [adjusted odds ratio (AOR)= 2.58; 95% CI= 1.13-5.89]. Patients with interstitial fibrosis and tubular atrophy (IFTA) &lt;25%, 25-50% and &gt;50% were observed in 10, 27 and 22 patients, respectively. Patients with IFTA &gt;50% were significantly associated with duration of diabetes (OR=1.27; 95%CI=1.21-1.57), serum creatinine (OR=3.92; 95%CI=1.34-11.48) and urine protein (OR= 1.25; 95%CI=1.01-1.55) compared with patients with IFA&lt;25%. Using multivariate analysis, only serum creatinine (AOR=3.48; 95%CI=1.23-12.65) was confirmed as independently correlated to IFTA &gt;50% compared with IFTA &lt;25%. A univariate analysis revealed no significant correlation between vascular indexes and renal function.&#x0D; Conclusion: The results revealed that advanced glomerular lesions and high IFTA &gt;50% correlated with impaired renal function in type 2 diabetic nephropathy

Effect of waterborne exposure to perfluorooctanoic acid on nephron and renal hemopoietic tissue of common carp Cyprinus carpio

Per- and poly-fluoroalkyl substances (PFAS) are synthetic contaminants of global concern for environmental and public health. Perfluorooctanoic acid (PFOA) is an important PFAS, and considerable attention has been paid to its hepatotoxicity and reproductive and developmental impact, while potential nephrotoxic effects are largely ignored, especially in fish. This study documents the structural and ultrastructural effects on kidney of common carp Cyprinus carpio exposed to waterborne PFOA at an environmentally relevant concentration of 200 ng L−1 and at 2 mg L−1. Dilation of the glomeruli capillary bed, increased vesiculation in the proximal tubular segment, compromised mitochondria, apical blebbing, and sloughing of collecting duct cells occurred in exposed fish, primarily at 2 mg L−1. Perfluorooctanoic acid exposure resulted in higher numbers of rodlet cells (RC), putative immune cells exclusive to fish, mainly in the renal interstitium, than seen in controls, increased association with cells of myeloid lineage and modifications to ultrastructure. No differences in other cells of innate immunity were observed.Despite the absence of severe histological lesions, PFOA was shown to affect both nephron and hemopoietic interstitium at high concentration, raising concern of the impact on renal and immune function in fish. The response of RCs to PFOA concentration of 200 ng L−1 suggests a potential role as a biomarker of PFOA exposure.

Histopathological Effects of Different Levels of Palm Kernel Cake Fed to Dorper Lambs

Palm kernel cake (PKC) is a nutrient-rich by-product of oil mills that contained a high concentration of copper (Cu) among other minerals elements. The higher dietary concentration of Cu was reported to impair some physiological functions in some breeds of sheep due to Cu toxicity. Hence, this study was aimed to investigate the histopathological effects of PKC based diet on vital organs of Dorper lambs. Fifteen male Dorper lambs (8 month-old) were randomly assigned to three treatment groups. Lambs were fed with a diet supplemented with different levels of PKC based on dry matter (DM) (PKC 750 gm kg-1 DM, PKC 700 gm kg-1 DM, and PKC 650 gm kg-1 DM) for 120 days. At the end of the experiment, all the lambs were slaughtered, liver, kidney, and testis samples were examined for gross pathological lesions. Microscopic examination showed that the liver of PKC75 group animals was histologically normal. However, cell hepatocyte abnormality was observed in PKC70 and PKC65 groups. No clinical symptoms or severe histological lesions were noticed in the kidney and testis of all groups. Therefore, the histomorphological normal organs observed indicated the PKC contents provided detoxification and immune defense in male lambs.

Effects of Fusarium metabolites beauvericin and enniatins alone or in mixture with deoxynivalenol on weaning piglets

The impact of the Fusarium-derived metabolites beauvericin, enniatin B and B1 (EB) alone or in combination with deoxynivalenol (DON) was investigated in 28–29 days old weaning piglets over a time period of 14 days. The co-application of EB and DON (EB + DON) led to a significant decrease in the weight gain of the animals. Liver enzyme activities in plasma were significantly decreased at day 14 in piglets receiving the EB + DON-containing diet compared to piglets receiving the control diet. All mycotoxin-contaminated diets led to moderate to severe histological lesions in the jejunum, the liver and lymph nodes. Shotgun metagenomics revealed a significant effect of EB-application on the gut microbiota. Our results provide novel insights into the harmful impact of emerging mycotoxins alone or with DON on the performance, gut health and immunological parameters in pigs.

Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy

AimsTo investigate serum soluble form of urokinase-type plasminogen activator receptor (suPAR) in patients with diabetic kidney disease (DKD) and biopsy-proven diabetic nephropathy (DN), its correlation with histological parameters and its capacity as a biomarker for renal impairment severity. MethodsWe conducted a cross-sectional study on 75 patients with diabetes mellitus (DM) and DKD, among whom 28 had biopsy-proven DN. ResultsAmong the 75 patients, 9 (12%) had type 1 and 66 (88%) type 2 DM. The median value of the serum suPAR level was 2857.2 pg/mL (1916.4–3700) in the entire cohort and 2472.1 pg/mL (1782.6–3745.8) in the biopsy-proven DN subgroup, respectively. suPAR was significantly correlated with diabetes duration, diabetic retinopathy, anti-proteinuric treatment, albuminuria, kidney function, DN class, interstitial fibrosis and tubular atrophy (IFTA) score and with interstitial inflammation score. suPAR had a good accuracy for the association with chronic kidney disease (CKD) stages G3b-5, macroalbuminuria, DN class IV, IFTA score 3 and interstitial inflammation score 2. ConclusionsSerum suPAR was increased in DN patients and was associated with DM duration, diabetic retinopathy, renoprotective treatment, kidney function, proteinuria, DN class, IFTA and interstitial inflammation scores. Also, suPAR had a good capacity as a biomarker for advanced renal impairment and severe histological lesions of DN.

Retrieved but not transplanted kidneys: how to limit the losses? A retrospective national study.

Despite the organ shortage, a significant number of deceased donor kidneys are retrieved but not transplanted (RNTK). This study aims to describe and analyze the main causes of potential grafts discard and to propose adequate solutions. We collected data from the Cristal database of the French Biomedicine Agency about RNTK over one year. Expert opinion was taken from urologists with extensive expertise in renal transplantation. They retrospectively analyzed each record to assess the appropriateness of each graft refusal and subsequent kidney discard. Of 252 kidneys were retrieved but not transplanted in France over one year. The main reasons for discard were vascular abnormalities in 43.7% (n=110), suspicion of malignant tumor in 18.7% (n=47), and severe histological lesions on preimplantation biopsy in 12.3% (n=31). The reason for kidney refusal was undetermined in 4.8% (n=12). Iatrogenic lesions were responsible for 26.2% (n=66). Overall, 46.0% (n=16) and 25.0% (n=63) of the grafts were, respectively, properly and improperly denied, and the analysis was not possible in 29.0% (n=73). In total, 36.9% of RNTK could have been transplanted. Reduction of iatrogenic lesions, improvement of microsurgical repair skills, and proper histological examination are necessary to reduce the number of RNTK. A prospective study applying the proposed principles is undoubtedly essential to complete this work.