Aging in the Canine Kidney.

Given the irreversible nature of nephron loss, aging of the kidney is of special interest to diagnostic and toxicologic pathologists. There are many similarities among histologic lesions in aged human and canine kidneys, including increased frequency of glomerulosclerosis, interstitial fibrosis, and tubular atrophy. Unfortunately, there are few studies in which renal tissue from aged healthy dogs was adequately examined with advanced diagnostics-namely, transmission electron microscopy and immunofluorescence-so age-associated changes in canine podocytes and glomerular basement membranes are poorly characterized. An age-associated decrease in the glomerular filtration rate in humans and dogs (specifically small breed dogs) has been documented. Although lesions in aged rats and mice differ somewhat from those of aged dogs and humans, the knowledge gained from rodent models is still vital to elucidating the pathogenesis of age-associated renal disease. Many novel molecules implicated in renal aging have been identified through genetically modified rodent models and transcriptomic and proteomic analysis of human kidneys. These molecules represent intriguing therapeutic targets and diagnostic biomarkers. Likewise, influencing critical pathways of cellular aging, such as telomere shortening, cellular senescence, and autophagy, could improve renal function in the elderly.

X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease.

Renal morphology in cats with diabetes mellitus.

In humans, diabetes mellitus (DM) is an important cause of renal damage, with glomerular lesions being predominant. In cats, although diabetes is a common endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of the study was to compare renal histologic features and parameters of renal function in diabetic cats against a control population matched for age, gender, breed, and body weight. Thirty-two diabetic and 20 control cats were included. Kidney sections from paraffin-embedded kidney samples were stained and examined with optical microscopy to identify glomerular, tubulointerstitial, and vascular lesions and to assess their frequency and severity. Serum creatinine and urea concentrations were also compared. Glomerular lesions were observed in 29 cats overall, with mesangial matrix increase being more common (19 cats). Tubulointerstitial lesions were observed in 42 cats, including lymphocytic infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were observed in 5 cases. The frequency and severity of histologic lesions did not differ between diabetic and control cats; however, among diabetics, those that survived longer after diagnosis had more glomerular and vascular lesions. Serum creatinine and urea concentrations were similar between groups; in diabetic cats median creatinine was 109 µmol/l (range, 51-1200) and urea was 12 mmol/l (range, 4-63), and in controls creatinine was 126 µmol/l (range, 50-875) and urea 11 mmol/l (range, 3-80). The results suggest that DM in cats does not lead to microscopically detectable kidney lesions or clinically relevant renal dysfunction. The authors hypothesize that the short life expectancy of diabetic cats may be the main reason for the difference from human diabetics.

Light and electron microscopic analysis of consecutive renal biopsy specimens from leishmania-seropositive dogs.

Canine visceral leishmaniasis frequently causes renal damage that leads to chronic kidney disease. Fifteen dogs seropositive for Leishmania were selected and biopsied before (T0) and 60 days later after (T1) treatment with a specific anti-Leishmania pharmacological agent. Various parameters were selected for evaluating the glomerular and tubulointerstitial damage. At T0, mesangioproliferative and membranoproliferative glomerulonephritis were observed in 6 dogs, chronic glomerulosclerosis in 5, and end-stage kidney in 3; renal tissue from 1 dog was within normal histologic limits. The most frequently observed ultrastructural changes were foot-process effacement, thickening of the basement membranes, and immune deposits. One dog had mesangial immune deposits at T1 that had not been present at T0, so the diagnosis was changed to mesangioproliferative glomerulonephritis. In dogs with end-stage kidney, the number of obsolescent glomeruli and cystic atrophied glomeruli was increased at T1. However, progression of the glomerular lesions was minimal in most dogs. Worsening of tubulointerstitial scores was evident in the dogs with the most severe lesions at the first biopsy. Progression of the tubulointerstitial damage was minimal in the mildly affected dogs, and the interstitial inflammation was abated. In conclusion, renal lesions can progress over a 60-day period in canine leishmaniasis. A longer period between the renal biopsies would be necessary to demonstrate more severe changes. In addition a specific anti-Leishmania treatment could have a significant effect in the early stages of the disease.

Leishmania amastigotes in neoplastic cells of 3 nonhistiocytic canine tumors.

Concurrent leishmaniasis and neoplasia has been reported in dogs. This study describes the presence of the protozoa within the cytoplasm of neoplastic cells in 3 different types of tumors. Leishmania amastigotes were detected by light and transmission electron microscopy and immunohistochemistry in a fibrosarcoma, a T-cell lymphoma, and an adrenocortical adenoma.

[Intracranial hydatid cysts in children: a report of 9 cases]. / Kystes hydatiques cérébraux de l'enfant (à propos de 9 cas).

PURPOSE: To illustrate the value of cross-sectional imaging (CT, MRI) for the diagnosis and follow-up of intracranial hydatid cysts in children. MATERIALS AND METHODS: Retrospective study of 9 cases of intracranial hydatid cysts in children seen over a period of 8 years. Precontrast and postcontrast 5 mm thick axial CT images were obtained in 7 cases. Noncontrast sagittal, axial and coronal T1W and T2W images were obtained in 2 cases. RESULTS: Mean patient age was 7.5 years. Intracranial hypertension was the main presenting clinical symptom. A single supratentorial cyst with significant mass effect upon the ventricular system and midline structures was observed in all cases. All patients underwent surgery with good outcome in all cases. CONCLUSION: CT is the imaging modality of choice for diagnosis and postoperative follow-up of intracranial hydatid cysts in children. MRI is most helpful for further characterization when multiple or atypical cysts are present to optimize management.

Potential biomarkers of preeclampsia: inverse correlation between hydrogen peroxide and nitric oxide early in maternal circulation and at term in placenta of women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disease that has been associated with future cardiovascular disease for the mother and her child. The etiology of PE is unclear but oxidative stress seems to play a major role in endothelial dysfunction and permanent systemic vasoconstriction shown in PE. Hydrogen peroxide (H(2)O(2)), a terminal metabolite of the cellular oxidative stress cascade, is also revealed as a component of oxidative ischemia/reperfusion stress in placenta. We were the first to show an increase in the levels of H(2)O(2) in the serum of preeclamptic women at term. H(2)O(2) is already known to reduce the production of NO by increasing the metabolism of arginases. The objective of this study was to investigate a possible correlation between nitric oxide (NO), a potent vasodilator, and H(2)O(2) throughout pregnancy. Thus, we simultaneously assessed the levels of NO and H(2)O(2) in the serum of normal and preeclamptic women at 10-15 and 37-40 weeks of pregnancy, and in placentas at delivery. Our findings showed an inverse correlation between increased levels of H(2)O(2) and decreased levels of NO early in maternal circulation and at term in placenta. This relationship is confirmed by our in vitro experiments which demonstrate that H(2)O(2) inhibits NO synthesis of cytotrophoblasts. In conclusion, our findings highlight an inverse correlation between H(2)O(2) and NO early in maternal circulation and in placenta of women with preeclampsia, paving the way for further studies examining the potential use of NO and H(2)O(2) as biomarkers in the prediction of preeclampsia.

[Giant cerebellar tuberculoma mimicking a malignant tumor]. / Tuberculome géant du cervelet simulant une tumeur maligne.

BACKGROUND: Isolated central nervous system (CNS) tuberculoma is rare. Central nervous system tuberculosis (TB) is associated with high morbidity and mortality despite modern methods of detection and treatment. The authors report a case of a giant cerebellar tuberculoma mimicking a malignant tumor and review the literature. OBSERVATION: A six-year-old girl, with no past medical history, vaccinated for her age, presented with a three-month history of occipitocervical cephalalgia, complicated by gait disturbances. The MRI showed a left cerebellar tumor suggestive of a medulloblastoma. At surgery, a nodular, avascular lesion was found and pathological examination confirmed tuberculoma. Intracranial tuberculoma is an uncommon variety of central nervous system tuberculosis. The prognosis is related to the rapidity of diagnosis, surgical resection and the complementary antituberculosis treatment. CONCLUSION: Intracranial tuberculoma is an uncommon variety of central nervous system infection. Prognosis is improved by a quick diagnosis, surgical removal, and associated antituberculoma therapy.

Investigation of the parameters used in fused deposition modeling of poly(lactic acid) to optimize 3D printing sessions.

This study assesses the feasibility of printing implantable devices using 3D printing Fused deposition modeling (FDM) technology. The influence of the deposition temperature, the deposition rate and the layer thickness on the printing process and the physical properties of the devices were evaluated. The filaments were composed of neat poly(lactic acid) (PLA) and blends of different plasticizers (polyethylene glycol 400 (PEG 400), triacetine (TA), acetyltriethyl citrate (ATEC) and triethyl citrate (TEC)) at 10% (w/w). The assessment of thermomechanical characteristics and morphology of both filaments and devices (cylinders and dog bones) were performed. The influence of each parameter was evaluated using a design of experiment (DoE) and the significance of the results was discussed. A large amount of data about the evaluation of FDM process parameters are already available in the literature. However, specific insights needed to be increased into the impact of the use of PLA and plasticized PLA raw material on the feasibility of printing devices in three dimensions. To conclude, the ductility was improved with a high layer thickness, low temperature and using ATEC. Whereas, adhesion was promoted with an increase in temperature, a lower layer thickness and adding TA.

Management of a severe cranio-orbito-facial trauma with a dislocation of the globe into the maxillary sinus.

We report two cases of severe cranio-orbito-facial trauma associated with a dislocation of the globe into the maxillary sinus. Simultaneous surgical repositioning the globe in the orbit and reconstruction of the orbital floor defect with an autogenous bone was performed in the first case. Postoperatively, the globe was in a normal position with a moderately reduced motility. The patient's visual acuity was reduced to light perception while indirect ophthalmoscopy was normal. In the second case, no surgery could be attempted because the patient never regained consciousness and died 7 days after the trauma. Although the visual prognosis of such conditions is usually considered to be extremely poor, avoiding primary enucleation and deploying all efforts to preserve the eye, aims at helping the patient to recover psychologically from the trauma and allows to improve her/his cosmetic aspect.

[Cerebral hydatic cyst and psychiatric disorders. Two cases]. / Kyste hydatique cérébral et troubles psychiatriques. A propos de deux cas.

The hydatidosis is an endemic illness in regions of the Middle Orient, Mediterranean, south of America, north Africa and the Australia. The preferential localization of cyst hydatic is the liver (48%), the lung (36%) and in 6% of cases it localizes in unaccustomed place as the brain. Intracerebral localization is relatively rare, its impact is 1 to 5% of all cases of hydatidose. This localization is the child's appendage with a masculine predominance. The cyst hydatic intracranien is often lone, of localization usually supratentorielle, sometimes infratentorielle. Symptoms are especially the diffuse headache associated to various neurological signs in relation with sits of the tumor. The psychiatrics symptoms depends on its localization, sides, intracranial hypertension, and the previous personality. In 15 to 20% of cases these tumors can appear in the beginning of their evolution by the isolated psychiatric symptoms. We report the case of two patients that have been hospitalized first in the Academic Psychiatric Unit of Marrakech for isolates psychiatric disorders and whose scanning revealed the presence of cerebral hydatic cyst and that required a surgical intervention in neurosurgery. Case 1 - Patient 29 years old, bachelor, uneducated, leaving in country outside, fermar, in permanent contact with dogs. No particular medical history. The patient has been brought by his family to the psychiatric emergencies after behavior disorders. The beginning of his symptomatology was one year ago by behavior disorders: instability, violence, isolation, and a corporo-sartorial carelessness. His symptomatology worsened and the patient became very aggressive. In psychiatric unit, he was disregarded, sad, anguished, indifferent to his state, very dissonant, completely detached, depersonalized. He brought back some visual and auditory hallucinations with attitude of monitoring. He was raving with delirium of persecution, of ideas of reference and delirium of bewithment. He was unconscious of his disorders. The patient has first been put under classical neuroleptic 9 mg/day of Haloperidol and 200 mg/day of chlorpromazine. The diagnosis of schizophrenia has been kept according to criteria of DSM IV. The PANSS (Positive and Negative Syndrome Scale) was to 137 (score on a positive scale was to 34, score on a negative scale was to 35 and the general psychopathologie scale was to 58). One week after his hospitalization, he developed headache with subconfusion, a cerebral scanning has been made in emergency and showed a voluminous cyst in oval foramen compressing the mesencephalon strongly. The cyst was well limited, hypodense, not taking the contrast, and without intracerebral oedema, the diagnosis of cerebral hydatic cyst has been made. The complementary exploration didn't show any other localizations, and biologic exam results didn't show any particular anomalies. The patient has been operated in neurosurgery. The immediate evolution was favorable with disappearance of confusion and absence of complications. The patient was lost of view. Six months after, the patient has been readmitted to the psychiatric emergency. He dropped his neuroleptic treatment. He was aggressive, raving, hallucinated and depersonalized. The global score to the PANSS was 63. He has been put back under neuroleptics. Three weeks after improvement and passage of the PANSS to 30, the patient went out. We couldn't have a cerebral scanner of control because the patient had no medical assurance and no money for cerebral scanner. Case 2 - Patient aged of 53 years, father of four children, uneducated, native and resident of Marrakech, confectioner as profession. He is in contact with dogs since 12 years. He has been brought to the psychiatric emergencies by his family after an agitation. The history of his illness seemed to go back at eight months ago, by the progressive apparition of an instability, sleep disorders, hostility, associated with an emotional lability. To the interview he was agitated and had a delirium of persecution. He was convinced that his wife and his children plotted against him. He had sad mood. He was anguished and had auditory and visual hallucinations. The patient was not confused but it had a hypoproxie, an fixing amnesia, a disorders of judgment and a light left hemiparesia. Cerebral scanner revealed three cerebral cyst. The first measuring 42 x 40 mm, sitting at the level parietal right, to the contact of the occipital horn, dragging his/her/its amputation and an effect of mass on ventricle homolateral, the median line and ventricle controlateral. The two other, at the level of the center semi oval, behind the first, measuring 23 mm and 15 mm on the big axis. The patient has been addressed in neurosurgery. He had a completeray exploration to search other localizations. The thoracic x-ray showed 2 pulmonary cyts. The abdominal scan and imagery by magnetic resonance showed liver cyst, peri-heart cyst and mediastinal cyst. The patient has been operated for these three cysts with good recuperation on the psychiatric and neurological symptoms. He has been addressed in heart surgery for the heart localization. The hydatidose is an endemic illness in Morocco and constitute a public health problem. The cerebral localization is rare and appear by signs of cerebral hypertension and signs of focusing. The psychiatric demonstrations are rare but preserve a major interest, by the therapeutic measure specificity that they impose. Of course, the surgical ablation of the tumor can be sufficient to attenuate the psychiatric symptoms but the recourse to a specific treatment can prove to be necessary to act on the precise targets. We are conscious of the methodological difficulties that present these 2 cases but there are unfortunately due to the financial difficulties of our patients.

[Cystic meningioma. Case report and literature review]. / Méningiome kystique. A propos d'un cas et revue de la littérature.

BACKGROUND: Cystic meningioma is a rare variety of meningioma. It represents 1,6 to 10% of intracranial meningiomas, the authors report a case of intracranial cystic meningioma with a review of literature. CASE REPORT: A 46-year-old female presented with left parietooccipital headache followed by right side hemiparesis. CT scan brain showed a left parietal tumor with double solid and cystic components thought to be glioma or metastasis preoperatively. At surgery the extraaxial solid and cystic lesion had a well defined capsule that could be easily separated from the perilesional cortical surface. The tumor was totally removed. The histological study showed a cystic meningioma. CONCLUSION: Cystic meningioma is an uncommon tumor that should be considered in the differential diagnosis of brain tumors with a cystic component.

[Intracranial aneurysm associated with aortic coarctation: a case report and literature review]. / Anévrisme intracrânien associé à une coarctation de l'aorte: à propos d'un cas et revue de la littérature.

We report a new and rare case associating an intracranial aneurysm and aortic coarctation. Based on this case and a review of the literature we discuss the clinical aspects, the pathogenesis and the management of this disorder predominantly observed in the adolescent and young adult population.

[Symptomatic intramedullary arachnoid cyst. Report of two cases and literature review]. / Kyste arachnoïdien intramédullaire symptomatique. A propos de deux cas et résumé de la littérature.

OBJECTIVE: The objective of this work is to present and discuss the rare situation of curable medullary compression with favorable prognosis. MATERIAL AND METHOD: Two cases of thoracic intramedullary arachnoid cysts are described. Clinical, paraclinical, therapeutics and outcome features are discussed with a review of the literature. RESULTS: Two children, 4 and 8 years old, with an uneventful history were admitted for progressive spastic paraparesia. MRI demonstrated a thoracic intramedullary cystic lesion at level T3-T4 in both patients. The cyst was emptied with partial cyst wall resection via dorsomedial myelotomy. The pathology examination confirmed the diagnosis of arachnoid cyst. The initial clinical signs resolved completely in both patients. CONCLUSION: Thought in children, intramedullary arachnoidian cyst is a potential cause of medullary compression. Direct surgery is the treatment of choice.

European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008-2015).

BACKGROUND: The European Veterinary Renal Pathology Service (EVRPS) is the first Web-based registry for canine renal biopsy specimens in Europe. HYPOTHESIS/OBJECTIVES: The aim was to verify whether differences exist between the clinical and laboratory presentation of dogs with nephropathy according to renal pathological findings, as defined by light and electron microscopy of renal biopsy specimens submitted to EVRPS. ANIMALS: Renal biopsy specimens of dogs were collected from the archive of the service (n = 254). Cases were included if both light and electron microscopy were available (n = 162). METHODS: Renal biopsy specimens were classified based on the morphological diagnoses. Thereafter, they were grouped into 3 disease categories, including immune-complex-mediated glomerulonephritis (ICGN), non-immune-complex-mediated GN (non-ICGN), and renal lesions not otherwise specified (RL-NOS). Differences among morphological diagnoses and among disease categories were investigated for clinical and laboratory variables. RESULTS: Serum albumin concentration was lower in dogs with ICGN than in those with non-ICGN (P = 0.006) or RL-NOS (P = 0.000), and the urine protein-to-creatinine ratio (UPC) was significantly higher in ICGN than in the other 2 disease categories. Regarding morphological diagnoses, albumin was significantly lower in amyloidosis (AMY) and membranous (MGN), membranoproliferative (MPGN) or mixed glomerulonephritis (MixGN) than in minimal change disease, primary (FSGS I) or secondary (FSGS II) focal and segmental glomerulosclerosis and juvenile nephropathies (JN). The UPC was higher in MPGN than in FSGS I and FSGS II. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with ICGN, in particular MPGN, had higher protein loss than those with non-ICGN or RL-NOS, leading to more severe hypoalbuminemia. Clinical and laboratory differentiation among dogs with the different morphological diagnoses and among dogs with different disease categories was difficult due to overlapping results.

[Giant osteoid osteoma of the posterior skull base. A case report and literature review]. / Ostéome ostéoïde géant de l'étage postérieur de la base du crâne. A propos d'un cas et revue de la littérature.

BACKGROUND: Osteoid osteoma is a benign bone neoplasm which is seen in the long bones. It is rarely described in the cranium. Posterior skull base osteoma is extremely rare and has been anecdotally reported. OBSERVATION: We report a rare case of a large osteoid osteoma of the petro-occipital area in a 26-year-old man. He presented with clinical sign of raised intracranial pressure, cerebellar symptoms and large left retro-auricular swelling. Cerebral MRI shows a giant lesion of the posterior cerebral fossa with destruction of the left petrous bone and the left side of the occipital bone. Large excision was performed through a retro-sigmoid approach. In our knowledge, there is no similar case reported in the literature to date. CONCLUSION: Although benign and rare, osteoid osteoma can present with neurological deficit due to mass effect and involvement of nervous structures especially in the posterior skull base.

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease.

BACKGROUND: Urine protein loss is common in dogs with chronic kidney disease (CKD). HYPOTHESIS/OBJECTIVES: To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. ANIMALS: One hunderd and eighty dogs with naturally occurring kidney disease. METHODS: Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. RESULTS: Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). CONCLUSIONS AND CLINICAL IMPORTANCE: Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.