Federico Valenza

Epithelial-mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis

Tubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker α-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered α-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans.

Membranoproliferative Glomerulonephritis Type III in a Simultaneous Infection of Leishmania Infantum and Dirofilaria Immitis in a Dog

In this report a 9-year-old female German Shepherd dog with a membranoproliferative glomerulonephritis (MPGN) type III associated with concomitant infection of Dirofilaria immitis and Leishmania infantum is presented. Light microscopic evaluation of kidney revealed a diffuse hypercellularity and thickening of glomerular basement membrane. Heavy and coarse granular complement C3 deposition and a weaker positive reaction to immunoglobulin G were present along peripheral glomerular basement membrane and in the mesangium in the immunofluorescent study. Transmission electron microscopy revealed deposits in the mesangium, subendothelium, and subepithelium. These lesions are compatible with membranoproliferative glomerulonephritis type III in humans.

Adenocarcinoma of the disseminated prostate in a cat

An adenocarcinoma of the disseminated prostate gland with pulmonary, myocardial and renal metastases is described in a 12-year-old, neutered male European cat. Histologically, the tumour was localised in the spongy layer of the prostatic urethra and showed an epithelial alveolar pattern. Considering the anatomic, microscopic and immunohistochemical findings, the tumour was diagnosed as an adenocarcinoma of the disseminated prostate gland. To our knowledge this is the first report of adenocarcinoma of the disseminated prostate gland in a cat.

Dog as model for down-expression of E-cadherin and β-catenin in tubular epithelial cells in renal fibrosis

Mechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial–mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin–catenin complex by immunohistochemistry of E-cadherin and β-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and β-catenin directly correlated with the tubular–interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). β-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies.

Bilateral juvenile renal dysplasia in a Norwegian Forest Cat

Renal dysplasia is defined as a condition of disorganised development of renal parenchyma due to abnormal differentiation. The case of a 5-month-old intact male Norwegian Forest Cat with a history of polyuria and polydipsia is reported. Ultrasonographic examination showed a slight enlargement of kidneys. Biochemical parameters, haematological examinations and clinical signs were compatible with chronic renal failure (CRF). Histological examination was correlated with a primary tubular disorganisation and modification of glomerular compartment. The clinical history together with the histological lesions is consistent with bilateral juvenile renal dysplasia in this cat. To our knowledge, feline renal dysplasia has been reported in fetal infections with panleukopenia virus; no reports indicate the idiopathic origin in feline dysplastic lesions.

Bovine cerebral theileriosis: Histological and ultrastructural investigations

Bovine cerebral theileriosis (BCT), or turning sickness is a clinical presentation of parasitic infections of cattle, caused by Theileria spp., that occurs sporadically in South Africa, Burundi, Uganda, Kenya and Tanzania. Clinical signs include circling, blindness, ataxia, opisthotonus and paralysis. The disease can be acute, subacute or chronic, and mainly affects animals between 3 and 5 years old. It is characterised by intense congestion and haemorrhages in the meninges and brain, encephalomalacia, and accumulation of parasitised lymphoblasts in cerebral blood vessels. Macroscopic, histological and ultrastructural lesions observed in 30 indigenous short-horn Zebu cattle from Northern Tanzania, aged 2–9-years-old, which presented characteristic neurological signs of a disease named “Ormilo” by local Maasai herders, were described. Brain smears, prepared from cerebral vessels and stained with Giemsa, revealed extensive lymphocytic infiltration associated with numerous schizonts. Histologically, areas of congestion and haemorrhage associated with obstruction of cerebral vessels with large numbers of parasitised lymphoblasts were the main lesions. Ultrastructural investigations demonstrated the presence of parasites morphologically comparable to flagellated protozoa inside lymphoid cells. This has never been described before in the end host (cattle), but only during the sexual stages within the gastrointestinal tract of ticks. PCR results showed positivity for Theileria taurotragi in 13 samples, suggesting that the parasite could be involved in the aetiology of Ormilo. The alternative hypothesis is that the parasite belongs to a different unknown protozoal genus, having an intra-lymphocytic phase, and being associated with infestation with Theileria spp. Further studies are needed to better understand the morphology of the parasite, its role in BCT, and its potential pathogenic importance for animals.

Severe meningeal fibrinoid vasculitis associated with Theileria taurotragi infection in two short-horned Zebu cattle

The Authors describe a severe vasculitis with fibrinoid necrosis of the meningeal arteries observed in two brains of indigenous short-horn zebu (Bos indicus) cattle, with bovine cerebral theileriosis (BCT) caused by a tick-transmitted hemoprotozoan, Theileria taurotragi, from Northern Tanzania. In the Author’s opinion, the role of T. taurotragi infection in the angiocentric and angiodestructive detected features remains to be evaluated. A possible immunopathologic cancerous mechanism, secondary to the lymphoid deregulation, could be involved. This report suggests further studies to better characterize the lymphoid cell involvement in the pathogenesis of the meningeal vascular lesions by T. taurotragi.