Characterization of an interdigitating dendritic cell hyperplasia case in a lymph node of a control C57BL/6 mouse.

Interdigitating dendritic cell (IDC) hyperplasia is considered a benign spontaneous condition occasionally observed in the lymph nodes of mice. It has been rarely reported and, to the best of our knowledge, it has never been characterized using immunohistochemistry. The present work describes a spontaneous IDC hyperplasia case in a lymph node of a 16-week-old control female C57BL/6 mouse. Microscopically, the lymph node architecture was completely effaced by the proliferation of eosinophilic spindle cells with an abundant pale cytoplasm forming trabecule admixed lymphocyte infiltrates. The spindle cell population was positive for F4/80, partially positive for S100 calcium-binding protein A4 (S100A4), slightly positive for E-cadherin, and negative for α-Smooth muscle actin (SMA) and cytokeratin. Lymphocytes were positive for CD3, CD4, CD20 and negative for CD8. Spindle cells were considered to be originated from the myeloid lineage, based on the immunohistochemistry (IHC) results, but their precise origin remains unclear (IDC or macrophages); even if macrophage origin is most likely based on F4/80 positivity, this remains to be further clarified using other markers.

Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat.

Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT/E (6.5 ng/kg) and BoNT/A (125 pg/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25N-ter and C-ter part; SNAP25C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25E and c-SNAP25A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT/A, BoNT/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles.

Identification of Mycobacterium genavense natural infection in a domestic ferret.

A 6-y-old neutered male ferret ( Mustela putorius furo) was presented because of a 1-mo history of progressive weight loss, chronic cough, and hair loss. On clinical examination, the animal was coughing, slightly depressed, moderately hypothermic, and had bilateral epiphora. Thoracic radiography was suggestive of severe multinodular interstitial pneumonia. Abdominal ultrasound examination revealed hepatosplenomegaly and mesenteric and pancreaticoduodenal lymphadenopathy. Fine-needle aspiration of the pancreaticoduodenal lymph node, followed by routine Romanowsky and Ziehl-Neelsen stains, revealed numerous macrophages containing myriad acid-fast bacilli, leading to identification of mycobacteriosis. Autopsy and histologic examination confirmed the presence of disseminated, poorly defined, acid-fast, bacilli-rich granulomas in the pancreaticoduodenal and mesenteric lymph nodes, intestines, and lungs. Destaining of May-Grünwald/Giemsa-stained slides with alcohol, and then restaining with Ziehl-Neelsen, revealed acid-fast rods and avoided repeat tissue sampling without affecting the Ziehl-Neelsen stain quality and cytologic features. Tissue samples were submitted for a PCR assay targeting the heat shock protein gene ( hsp65) and revealed 100% homology with Mycobacterium genavense. We emphasize the use of special stains and PCR for identification of this potential zoonotic agent.

Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model.

Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.

Plasma heme-induced renal toxicity is related to a capillary rarefaction.

Severe hypertension can lead to malignant hypertension (MH) with renal thrombotic microangiopathy and hemolysis. The role of plasma heme release in this setting is unknown. We aimed at evaluating the effect of a mild plasma heme increase by hemin administration in angiotensin II (AngII)-mediated hypertensive rats. Prevalence of MH and blood pressure values were similar in AngII and AngII + hemin groups. MH rats displayed a decreased renal blood flow (RBF), increased renal vascular resistances (RVR), and increased aorta and interlobar arteries remodeling with a severe renal microcirculation assessed by peritubular capillaries (PTC) rarefaction. Hemin-treated rats with or without AngII displayed also a decreased RBF and increased RVR explained only by PCT rarefaction. In AngII rats, RBF was similar to controls (with increased RVR). PTC density appeared strongly correlated to tubular damage score (rho = -0.65, p < 0.0001) and also renal Heme Oygenase-1 (HO-1) mRNA (rho = -0.67, p < 0.0001). HO-1 was expressed in PTC and renal tubules in MH rats, but only in PTC in other groups. In conclusion, though increased plasma heme does not play a role in triggering or aggravating MH, heme release appears as a relevant toxic mediator leading to renal impairment, primarily through PTC endothelial dysfunction rather than direct tubular toxicity.

Experimental models of renal calcium stones in rodents.

In human nephrolithiasis, most stones are containing calcium and are located within urinary cavities; they may contain monohydrate calcium oxalate, dihydrate calcium oxalate and/or calcium phosphates in various proportion. Nephrolithiasis may also be associated with nephrocalcinosis, i.e., crystal depositions in tubular lumen and/or interstitium, an entity which suggests specific pathological processes. Several rodents models have been developed in order to study the pathophysiology of intrarenal crystal formation. We review here calcium rodent models classified upon the presence of nephrolithiasis and/or nephrocalcinosis. As rodents are not prone to nephrolithiasis, models require the induction of a long standing hypercalciuria or hyperoxaluria (thus explaining the very few studies reported), conversely to nephrocalcinosis which may occur within hours or days. Whereas a nephrotoxicity leading to tubular injury and regeneration appears as a critical event for crystal retention in nephrocalcinosis models, surprisingly very little is known about the physiopathology of crystal attachment to urothelium in nephrolithiasis. Creating new models of nephrolithiasis especially in different genetic mice strains appears an important challenge in order to unravel the early mechanisms of urinary stone formation in papilla and fornices.