Accumulation Of PAS-positive Material Research Articles

The Role of Diabetic Choroidopathy in the Pathogenesis and Progression of Diabetic Retinopathy.

Diabetic choroidopathy was first described on histopathological specimens of diabetic eyes. This alteration was characterized by the accumulation of PAS-positive material within the intracapillary stroma. Inflammation and polymorphonuclear neutrophils (PMNs) activation are crucial elements in choriocapillaris impairment. The evidence of diabetic choroidopathy in vivo was confirmed with multimodal imaging, which provides key quantitative and qualitative features to characterize the choroidal involvement. The choroid can be virtually affected in each vascular layer, from Haller's layer to the choriocapillaris. However, the damage on the outer retina and photoreceptor cells is essentially driven by a choriocapillaris deficiency, which can be assessed through optical coherence tomography angiography (OCTA). The identification of characteristic features of diabetic choroidopathy can be significant for understanding the potential pathogenic and prognostic implications in diabetic retinopathy.

Intestinal failure and transplantation in microvillous inclusion disease

Abstract Introduction Microvillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhoea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation. Patients and methods A retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013. Results All debuted in the first month of life, with a median age of three days (range, 3–30 days), and had secretory diarrhoea dependent on parenteral nutrition, with fasting faecal volume of 150–200 ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.

Fracaso intestinal y trasplante en la enfermedad por inclusiones microvellositarias

IntroductionMicrovillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation. Patients and methodsA retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013. ResultsAll debuted in the first month of life, with a median age of three days (range, 3-30 days), and had secretory diarrhea dependent on parenteral nutrition, with fasting fecal volume of 150-200ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.

Pathobiochemical aspects of diabetic nephropathy.

Diabetic nephropathy develops in many diabetic patients as consequence of glomerulosclerosis. On the basis of a series of recent observations it is suggested that a combination of metabolic and hemodynamic changes is responsible for the pathogenesis of diabetic nephropathy. Since the glomerular filtration unit has been characterized to consist of collagen type IV and minor components like laminin, fibronectin and heparan sulfate proteoglycan, influence of diabetes on basement membrane (BM) components has been studied. Biochemical alterations of glomerular BM consist of an increased nonenzymatic glucosylation of type IV collagen leading to unphysiological crosslinking. This, in turn, may result in alteration of the size selective properties of the glomerular filtration unit. Changes in composition of glomerular BM have recently been described. An increased synthesis of type IV collagen with concomitant decrease of heparan sulfate proteoglycan may lead to alteration of the charge selective barrier and consequently to increased permeability of the glomerular BM. Permanently unbalanced synthesis of BM components finally results in obliteration of the capillary lumen. In late state nephropathy intrinsic basement membrane components are no longer produced. Instead, massive accumulation of PAS positive material occurs.

Acute Bilirubin Encephalopathy Induced with Sulfadimethoxine in Gunn Rats

Acute bilirubin encephalopathy was induced in young Gunn rats with a sulfonamide (sulfadimethoxine), which acts by competitive displacement of bilirubin from albumin binding sites, in order to study the differences between the spontaneously occurring neuronal degeneration described in Gunn rats (18) and the acute neurotoxic effects of bilirubin. Thirty 14 day old homozygous Gunn rats were injected with sulfadimethoxine, 50 mg/kg twice daily s.c. All treated rats developed signs of neurotoxicity within a few hours and were sacrificed by intracardiac perfusion with fixative after 6–12 hours (4 rats), 13–24 hours (12 rats), 25–48 hours (9 rats) and 49–103 hours (5 rats). The brains of fourteen treated animals showed regional yellow staining. Microscopic examination showed two different types of lesions: (1) all brains showed neuronal degeneration with accumulation of PAS-positive material and formation of membranous bodies (MB's) which was most marked in the areas with localized yellow staining, (2) acute necrotic lesions were present in the hippocampal formation, inferior colliculi, globus pallidus and in the ponto-medullary tegmentum in 8 of 13 animals which were sacrificed no less than 24 hours after the first injection. Ultrastructural examination of these acute necrotic lesions showed enlarged extracellular spaces, swelling of astrocytic processes and two types of neuronal cytolysis: (a) large ‘watery’ neurons with swollen cell bodies and (b) small neurons with shrunken cytoplasm, loss of organelles and electron-dense nuclei. The brains of control rats (5 untreated and 6 asphyxiated homozygous rats and 10 treated heterozygous litter-mates of the experimental rats) showed no abnormalities other than neuronal degeneration with MB formation. It is concluded that both processes, the neuronal degeneration with MB formation and acute necrotic lesions with neuronal cytolysis, represent two different tissue responses to the toxic effect of bilirubin. Neuronal degeneration with MB formation appears to result from prolonged exposure to relatively low concentrations of tissue bilirubin. The acute focal necrotic lesions are

PHOTOSENSITIVE BULLOUS ERUPTION ASSOCIATED WITH CHRONIC RENAL FAILURE*

SummaryEight patients with chronic renal failure developed blisters similar to those seen in porphyria cutanea tarda. However, porphyrin studies were normal and neither scarring nor milia were seen in these patients. Blistering appeared to be induced by minor trauma to light exposed areas on the dorsa of the hands and feet, and intensity of sunlight seemed more related to blister production than either the type or severity of renal disease or the patient's medication. The blisters were produced by a split at the dermo‐epidermal junction just above the PAS basement membrane zone. The upper dermal blood vessels within the region were thickened by the accumulation of PAS positive material. Although there was little cellular infiltrate, many degranulated mast cells were present in the mid‐dermis. Deviating calciphylaxis may have been associated with these changes.